Antipsychotic switching tool

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. Start brexpiprazole 1 mg in the morning on day 1 and slowly increase the dose in steps during the period of cariprazine elimination. The dose range of brexpiprazole is 1–4 mg daily.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start amisulpride on day 1 at 200 mg to avoid acute dystonia and increase slowly to the target dose, over the period of cariprazine elimination. Increase the dose of amisulpride slowly to a therapeutic dose during the period of cariprazine elimination. For positive symptoms of psychosis, the target dose of amisulpride is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction than cariprazine. As amisulpride has an elevated risk of QTc prolongation, it is recommended to check serum magnesium, potassium and an ECG before administration.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start asenapine at 5 mg twice a day on day 1 and slowly increase the dose in steps as required, during the period of cariprazine elimination. The therapeutic dose of asenapine is 10–20 mg daily.

Expect asenapine to be more sedating than cariprazine and more likely to cause postural hypotension. The risk of weight gain is higher with asenapine than with cariprazine.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

If the target dose of chlorpromazine is known, slowly increase the dose in steps to reduce the anticholinergic and hypotensive adverse effects, during the period of cariprazine elimination.

If the target dose is not known, be guided by the patient’s previous drug history to estimate the chlorpromazine dose. The dose range of chlorpromazine is 200–800 mg daily.

Chlorpromazine is more likely to cause anticholinergic adverse effects, postural hypotension, sedation and increased prolactin than cariprazine.

Direct switch

The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Stop cariprazine. Start clozapine immediately according to standard titration schedules (from 12.5 mg or 25 mg), and increase the dose slowly as required during the period of cariprazine elimination. (An effective dose of clozapine is generally from 200 mg daily or when clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect.)

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start haloperidol on day 1 at 1 mg in order to minimise effects such as dystonia. Slowly increase haloperidol in steps during the period of cariprazine elimination. The therapeutic dose range of haloperidol is 1–5 mg daily.

Haloperidol is more likely to cause extrapyramidal effects and increase prolactin than cariprazine. It is also likely to have some dysphoric effect, particularly after the use of partial dopamine agonists.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start lurasidone at 40 mg once daily on day 1. This may be an effective dose for some patients. Dose titration can be undertaken if clinically indicated over the period of cariprazine elimination. For most patients, optimal clinical response and tolerability with lurasidone is expected at 40 or 80 mg once daily, doses up to 160 mg a day may be needed.

Lurasidone should be taken with food.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Olanzapine should be started at night on day 1 at a low dose (e.g. 5 mg). Olanzapine should then be increased slowly in steps over the period of cariprazine elimination. The dose range of olanzapine is 5–20 mg daily, and the dose should be adjusted according to clinical response and adverse effects.

Olanzapine will be more sedating than cariprazine and is likely to cause significantly more weight gain.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Paliperidone should be started at a low dose on day 1 and increased slowly (at intervals of at least 5 days), as necessary, during the period of cariprazine elimination. The dose range of paliperidone is 3–12 mg daily.

The patient should be advised to take paliperidone at the same time in relation to food intake and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Paliperidone is more likely to increase prolactin than cariprazine.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Periciazine may be started at a low dose on day 1 and increased slowly as required over the period of cariprazine elimination. The dose of periciazine depends on the indication ranging from 2.5 mg to 75 mg daily in divided doses.

Periciazine is likely to be more sedating, have more anticholinergic effects, and possibly cause more extrapyramidal adverse effects, than cariprazine.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start quetiapine at a low dose on day 1 (e.g. 50 mg extended-release or 25 mg twice-daily immediate release). Quetiapine should then be gradually increased in steps depending on response over the period of cariprazine elimination.

The usual effective daily dose of quetiapine is 300–450 mg. Lower doses are generally used for bipolar depression than for mania and schizophrenia. Depending on the clinical response and tolerability, the daily dose of quetiapine may be adjusted within a range of 200–800 mg.

Quetiapine will be more sedating and is likely to have more anticholinergic effects than cariprazine.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Start risperidone on day 1 at a low dose, such as 1 mg daily, then increase gradually to the target dose during the period of cariprazine elimination. If the target dose is unknown, slowly increase the dose from 1 mg daily depending on the response. The dose of risperidone is 1–6 mg daily, given in one or two doses.

Risperidone is more likely to increase prolactin than cariprazine.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Ziprasidone should be commenced at a low dose (e.g. 40 mg) on day 1 and increased gradually to the target dose during the period of cariprazine elimination. If the target dose is not known, it is recommended to start ziprasidone at 40 mg daily and slowly adjust the dose depending on clinical effects. The recommended dose range of ziprasidone is 80–160 mg daily, given in one or two doses.

Ziprasidone has a higher risk of QTc prolongation than cariprazine. It is recommended to check serum magnesium, potassium and an ECG before administration.

Ziprasidone should be taken with food.

Direct switch

Cariprazine can be stopped on day 1. The long effective half-life of cariprazine (about 7 days) means withdrawal effects are unlikely. It may take 3–4 weeks for most of the cariprazine to be eliminated.

Zuclopenthixol should be started at a low dose on day 1 (e.g. 10 mg) and increased slowly to the target dose during the period of cariprazine elimination.

If the target dose is not known, start zuclopenthixol at 10 mg daily and adjust the dose slowly based on clinical effects. The dose range of zuclopenthixol is 10–75 mg daily, depending on the indication.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin than cariprazine.

Direct switch

Due to differences in adverse effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

Start cariprazine and simultaneously commence reduction of amisulpride gradually in steps over about 4 weeks during the period of cariprazine initiation. If the original dose of amisulpride is 200 mg or less, it is advisable not to start reducing it for at least the first 3 weeks after starting cariprazine.

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch or cross titration

The half-life of aripiprazole is long (approximately 75 hours). Most of the drug is eliminated two weeks after stopping. It can be stopped immediately with little risk of withdrawal effects. When switching to cariprazine, cross titration may be used if there is concern about maintaining adequate antipsychotic treatment.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

Start cariprazine on day 1 and at the same time cease or reduce aripiprazole over the period of cariprazine titration. The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose of cariprazine can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability, to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

Start cariprazine and simultaneously commence reduction of asenapine gradually in steps over about 4 weeks during the period of cariprazine initiation. If the original dose of asenapine is 5 mg, it is advisable not to start reducing it for at least the first 3 weeks after starting cariprazine.

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch or cross titration

The half-life of brexpiprazole is long (approximately 91 hours). Most of the drug is eliminated 2.5 weeks after stopping. It can be stopped immediately with little risk of withdrawal effects. When switching to cariprazine, cross titration could be used if there is concern about maintaining adequate antipsychotic treatment.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

Start cariprazine on day 1. Cease or reduce brexpiprazole over the period of cariprazine titration. The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

A direct switch is not recommended because of the differences in adverse effect properties of the two drugs. Chlorpromazine should be stopped slowly to avoid anticholinergic withdrawal, possible blood pressure effects, and behavioural effects related to loss of sedation.

Cross titration

Reduce the chlorpromazine dose slowly in steps over a period of about 4 weeks while cariprazine is started on day 1. Cariprazine has no anticholinergic effects so there is some risk of cholinergic withdrawal after stopping chlorpromazine.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks). If the original dose of chlorpromazine is 200 mg or less, it is advisable not to start reducing it for at least the first 3 weeks after cariprazine therapy.

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt stopping of clozapine carries a high risk of withdrawal psychosis and withdrawal anticholinergic symptoms. If withdrawal psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

Start cariprazine on day 1. If possible, reduce clozapine slowly over 6 weeks (very high-risk patients should stop clozapine over 3–6 months). The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. The dose of cariprazine can be titrated gradually during the period of clozapine withdrawal. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce haloperidol gradually in steps over a period of about 4 weeks while cariprazine is started on day 1. If the original dose of haloperidol is 2 mg or less, it is advisable not to start reducing it for at least the first 3 weeks after starting cariprazine.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce lurasidone gradually in steps over a period of about 4 weeks while cariprazine is started on day 1. If the original dose of lurasidone is 40 mg or less, it is advisable not to start reducing it for at least the first 3 weeks after starting cariprazine.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce olanzapine gradually in steps over a period of about 4 weeks while cariprazine is started on day 1. Slow reduction of olanzapine will minimise risk of anticholinergic withdrawal symptoms and insomnia.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce paliperidone gradually in steps over a period of about 4 weeks while cariprazine is started on day 1.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce periciazine gradually in steps over a period of about 4 weeks while cariprazine is started on day 1.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce quetiapine (both immediate release and modified release) gradually in steps over a period of about 4 weeks while cariprazine is started on day 1. Slow reduction of quetiapine will minimise risk of anticholinergic withdrawal symptoms and insomnia.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce risperidone gradually in steps over a period of 4 weeks while cariprazine is started on day 1.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce ziprasidone gradually in steps over a period of about 4 weeks while cariprazine is started on day 1.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch

Due to differences in adverse-effect profiles and half-lives, a direct switch is not recommended.

Cross titration

Reduce zuclopenthixol gradually in steps over a period of about 4 weeks while cariprazine is started on day 1.

Cariprazine has a long effective half-life (about 7 days) and will take 4–5 weeks to reach steady-state concentrations (90% of steady state is achieved in 3 weeks).

The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be increased (preferably slowly to reduce activation effects) in 1.5 mg increments according to efficacy and tolerability to a maximum daily dose of 6 mg, if needed. Technically the interval between cariprazine dose adjustments should be at least two weeks. When clinically necessary, adjustments can be made at shorter intervals such as weekly (observe for adverse effects).

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction. There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin. There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin. There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of causing QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken. There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin and cause extrapyramidal effects.

Stop zuclopenthixol.

Patients should be initially converted to oral risperidone to exclude hypersensitivity or allergy which may manifest with a variety of symptoms including angioedema, urticaria and rash. Tablets may be started while the patient still has significant zuclopenthixol plasma concentrations from the depot. If starting oral risperidone within a week of the last zuclopenthixol depot, give 25% of the target dose and titrate up according to clinical effects.

Risperidone depot has a 3-week lag before significant release of risperidone from the injection. When converting from oral to depot risperidone, continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage in that period.

If converting to risperidone depot without using oral risperidone, the risperidone depot should be started 3 weeks before the next dose of zuclopenthixol was to be given. This avoids a significant trough in antipsychotic concentrations. Zuclopenthixol is most commonly given every 2 weeks which creates a complicated situation. Another zuclopenthixol dose must be given after the first risperidone dose is given because there is a risk of breakthrough symptoms before the risperidone depot starts to release.

Stop zuclopenthixol.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant zuclopenthixol plasma concentrations. If starting oral olanzapine within a week of the last zuclopenthixol depot, give 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, switch directly from zuclopenthixol depot to olanzapine depot. In this case, the first olanzapine depot should be given on the day that the zuclopenthixol depot was next due.

Olanzapine is more sedating than other antipsychotic depot drugs. Because of the risk of post-injection syndrome, the patient must be observed for 2 hours after each injection of olanzapine depot.

Stop zuclopenthixol.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next zuclopenthixol depot dose was to be given. If converting the patient in this way, the loading dose regimen for paliperidone should not be used. Patients can only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for use in patients who have not been stabilised on the 4-weekly paliperidone depot for at least 4 months.

Stop zuclopenthixol.

Patients should be initially converted to oral haloperidol to exclude allergy. Tablets may be started while the patient still has significant zuclopenthixol plasma concentrations from the depot. If starting oral haloperidol within a week of the last zuclopenthixol depot, give 25% of the target dose.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions, the full dose of haloperidol depot can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of zuclopenthixol depot can be used to guide the target dose of the haloperidol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop zuclopenthixol.

Start flupentixol on the day zuclopenthixol depot was due.

If the patient has not had flupentixol before, give a test dose of 5–20 mg 5–10 days before the flupentixol is to be started. If there are no reactions, on the day the zuclopenthixol depot was due, the full dose of flupentixol can be given.

The dose of zuclopenthixol can be used to guide the target dose of flupentixol depot. Previous antipsychotic use from the patient’s history may also be a helpful guide.

Stop zuclopenthixol.

Patients should be initially converted to oral aripiprazole to exclude allergy. Start oral aripiprazole at the target dose on the day that zuclopenthixol depot was due. The recommended starting dose for aripiprazole is 10–20 mg daily, although some guidance can be taken from the dose of zuclopenthixol depot that was used. Two weeks of oral therapy is recommended to establish tolerability before the first aripiprazole depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks for all patients except those who are known to be poor cytochrome P450 2D6 metabolisers or have demonstrated sensitivity to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, changing to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability, as well as psychotic relapse.

Stop risperidone

There is a delay of approximately 3 weeks following the last risperidone injection before the drug starts to release. The switch to zuclopenthixol should therefore be designed to avoid increasing peak antipsychotic concentrations. The most commonly suggested method is to delay the first dose of zuclopenthixol by 4 to 6 weeks. Another method, recommended in this tool, is to continue the regular injection cycle, to aid adherence, but start zuclopenthixol at a lower dose. This is based on the authors’ clinical experience of problems encountered when the injection cycle is broken.

Patients should be initially converted to oral zuclopenthixol tablets to exclude allergy. Oral zuclopenthixol may be started while the patient still has significant risperidone plasma concentrations from the depot. If starting oral zuclopenthixol within 3 weeks of the last injection of risperidone, the dose should be approximately 25% of the target dose.

If the patient has not had zuclopenthixol before and oral zuclopenthixol cannot be used, aim to start zuclopenthixol depot on the day the risperidone depot was due. Give a test dose of 50 mg of zuclopenthixol depot 5–10 days before the zuclopenthixol depot is to be started. If there are no reactions and it is within 3 weeks of the last injection of risperidone, the dose should be approximately 25% of the target dose, otherwise give the full dose on the day the risperidone depot was due.

If the patient is converting from oral to depot zuclopenthixol, oral zuclopenthixol should be continued for at least 1 week after the start of the zuclopenthixol depot.

The dose of risperidone depot can be used to guide the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop risperidone.

Paliperidone depot can be given on the day that the next risperidone depot was due. If converting the patient in this way, the loading dose regimen for paliperidone should not be used. Patients can only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for use in patients who have not been stabilised on the 4-weekly paliperidone depot for at least 4 months.

Stop risperidone.

There is a delay of approximately 3 weeks following the last risperidone injection before the drug starts to release. The switch to olanzapine should therefore be designed to avoid increasing peak antipsychotic concentrations. The most commonly suggested method is to delay the first dose of olanzapine by 4 to 6 weeks. Another method, recommended in this tool, is to continue the regular injection cycle, to aid adherence, but start olanzapine at a lower dose. This is based on the authors’ clinical experience of problems encountered when the injection cycle is broken.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant risperidone plasma concentrations. If starting oral olanzapine within 3 weeks of the last injection of risperidone, the dose should be approximately 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, it is possible to switch directly from risperidone depot to olanzapine depot. In this case, aim to start olanzapine depot on the day risperidone depot was due. If it is within five weeks of the last time risperidone depot was administered, the dose should be approximately 25% of the target dose, otherwise give the full dose on the day the risperidone depot was due.

Olanzapine is more sedating than other antipsychotic depots. Because of the risk of post-injection syndrome, the patient must be observed for 2 hours after each olanzapine injection.

Stop risperidone.

There is a delay of approximately 3 weeks following the last risperidone injection before the drug starts to release. The switch to haloperidol should therefore be designed to avoid increasing peak antipsychotic concentrations. The most commonly suggested method is to delay the first dose of haloperidol by 4 to 6 weeks. Another method, recommended in this tool, is to continue the regular injection cycle, to aid adherence, but start haloperidol at a lower dose. This is based on the authors’ clinical experience of problems encountered when the injection cycle is broken.

Patients should be initially converted to oral haloperidol to exclude allergy. Tablets may be started within 3 weeks of the last injection of risperidone even though the patient still has significant risperidone plasma concentrations from the depot. The oral haloperidol dose should be approximately 25% of the target dose.

Aim to start haloperidol depot on the day risperidone depot was due.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions and it is within 3 weeks of the last injection of risperidone, the dose should be approximately 25% of the target dose, otherwise give the full dose on the day the risperidone depot was due.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of risperidone depot can be used as a rough guide to the target dose of haloperidol depot. Previous antipsychotic use from the patient’s history may also give a guide as to the target dose of haloperidol depot.

Stop risperidone.

There is a delay of approximately 3 weeks following the last risperidone injection before the drug starts to release. The switch to flupentixol should therefore be designed to avoid increasing peak antipsychotic concentrations. The most commonly suggested method is to delay the first dose of flupentixol by 4 to 6 weeks. Another method, recommended in this tool, is to continue the regular injection cycle, to aid adherence, but start flupentixol at a lower dose. This is based on the authors’ clinical experience of problems encountered when the injection cycle is broken.

Aim to start flupentixol on the day risperidone depot was due.

If the patient has not had flupentixol before, give a test dose of 5–20 mg 5–10 days before the flupentixol is to be started. If there are no reactions and it is within 3 weeks of the last injection of risperidone, the dose should be approximately 25% of the target dose, otherwise give the full dose on the day the risperidone depot was due.

The dose of risperidone can be used to guide the target dose of flupentixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop risperidone.

There is a delay of approximately 3 weeks following the last risperidone injection before the drug starts to release. The switch to aripiprazole should therefore be designed to avoid increasing peak antipsychotic concentrations. The most commonly suggested method is to delay the first dose of aripiprazole by 4 to 6 weeks. Another method, recommended in this tool, is to continue the regular injection cycle, to aid adherence, but start aripiprazole at a lower dose. This is based on the authors’ clinical experience of problems encountered when the injection cycle is broken.

Patients should be initially switched from risperidone depot to oral aripiprazole. If starting oral aripiprazole within 3 weeks of the last injection of risperidone, the dose of aripiprazole should be approximately 25% of the target dose. If the target dose is unknown, the recommended starting dose for aripiprazole is 10–20 mg daily, although some guidance can be taken from the dose of risperidone depot that was used.

Two weeks of oral aripiprazole is recommended to establish tolerability. The recommended dose of aripiprazole depot is 400 mg every 4 weeks for all patients except those who are known to be poor cytochrome P450 2D6 metabolisers or have had adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, changing to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

Patients should be initially converted to oral zuclopenthixol tablets to exclude allergy and establish tolerability. Oral zuclopenthixol may be started while the patient still has significant paliperidone plasma concentrations from the depot. If starting oral zuclopenthixol within a week of the last paliperidone depot, give 25% of the target dose.

If the patient has not had zuclopenthixol before and oral zuclopenthixol cannot be used, give a test dose of 50 mg of zuclopenthixol depot 5–10 days before the zuclopenthixol depot is to be started. If there are no reactions, give the full dose of zuclopenthixol depot.

The dose of paliperidone depot can be used to guide the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop paliperidone.

Risperidone depot has a 3-week lag before significant release of risperidone from the injection site so it can be started 3 weeks before the next dose of paliperidone depot was due. Because of the long half-life of paliperidone depot, oral risperidone supplementation is regarded as unnecessary.

Stop paliperidone.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Tablets may be started while the patient still has significant paliperidone plasma concentrations. If starting oral olanzapine within a week of the last paliperidone depot, give 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, switch paliperidone depot directly to olanzapine depot. In this case, the first olanzapine depot should be given on the day that the paliperidone depot was next due.

Olanzapine is more sedating than other antipsychotic depots. Because of the risk of post-injection syndrome, the patient must be observed for 2 hours after each olanzapine injection.

Stop paliperidone.

Patients should be initially converted to oral haloperidol to exclude allergy. Tablets may be started while the patient still has significant paliperidone plasma concentrations from the depot. If starting oral haloperidol within a week of the last paliperidone depot, give 25% of the target dose.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions, the full dose can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of paliperidone depot can be used as a rough guide to the target dose of haloperidol depot. Previous antipsychotic use from the patient’s history may also give a guide as to the target dose of haloperidol depot.

Stop paliperidone.

Start flupentixol on the day paliperidone depot was due.

If the patient has not had flupentixol before give a test dose of 5–20 mg 5–10 days before the flupentixol is to be started. If there are no reactions, give the full dose.

The dose of paliperidone can be used to guide the target dose of flupentixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop paliperidone.

Convert paliperidone depot to oral aripiprazole by starting the oral aripiprazole at the target dose on the day that paliperidone depot was due. The recommended starting dose for aripiprazole is 10–20 mg daily, although some guidance can be taken from the dose of paliperidone depot that was used. Two weeks of oral therapy is recommended to establish tolerability to aripiprazole before the first depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks for all patients except those who are known to be poor cytochrome P450 2D6 metabolisers or were sensitive to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, changing to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

Stop olanzapine.

Patients should be initially converted to oral zuclopenthixol to exclude allergy. Tablets may be started while the patient still has significant olanzapine plasma concentrations from the depot. If starting oral zuclopenthixol within a week of the last olanzapine depot, give 25% of the target dose.

If the patient has not had zuclopenthixol before and oral zuclopenthixol cannot be used, give a test dose of 50 mg of zuclopenthixol depot 5–10 days before the zuclopenthixol depot is to be started. If there are no reactions, the full dose of zuclopenthixol depot can be given.

If the patient is converting from oral to depot zuclopenthixol, oral zuclopenthixol should be continued for at least 1 week after the start of depot treatment.

The dose of olanzapine depot can be used to guide the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also be a helpful guide.

Stop olanzapine.

Patients should be initially converted to oral risperidone to exclude hypersensitivity or allergy which may manifest with symptoms including angioedema, urticaria and rash. Tablets may be started while the patient still has significant olanzapine plasma concentrations from the depot. If starting oral risperidone within a week of the last olanzapine depot, give 25% of the target dose and titrate up according to clinical effects.

Risperidone depot has a 3-week lag before significant release of risperidone from the injection site so risperidone depot can be started 3 weeks before the next dose of olanzapine depot was to be given.

When converting from oral to depot risperidone, continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage in that period.

If olanzapine depot was given as a 2-weekly injection and it is intended to convert to risperidone depot without using oral risperidone, a complicated situation arises. Another olanzapine dose must be given after the first risperidone dose is given because there is a risk of breakthrough symptoms before the risperidone depot starts to release. Clinicians must weigh the risks and benefits of converting to risperidone without using oral risperidone as a bridge.

Stop olanzapine.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next olanzapine depot was due. If converting the patient in this way, the loading dose regimen for paliperidone should not be used. Patients can only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for use in patients who have not been stabilised on the 4-weekly paliperidone depot for at least 4 months.

Stop olanzapine.

Patients should be initially converted to oral haloperidol to exclude allergy. Tablets may be started while the patient still has significant olanzapine plasma concentrations from the depot. If starting oral haloperidol within a week of the last olanzapine depot, give 25% of the target dose.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions, the full dose of haloperidol depot can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of olanzapine depot can be used to guide the target dose of haloperidol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop olanzapine.

Start flupentixol depot on the day olanzapine depot was due.

If the patient has not had flupentixol before, give a test dose of 5–20 mg 5–10 days before the flupentixol is to be started. If there are no reactions, the full dose of flupentixol can be given.

The dose of olanzapine can be used to guide the target dose of flupentixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop olanzapine.

Start oral aripiprazole at the target dose on the day that olanzapine depot was due. The recommended starting dose for aripiprazole is 10–20 mg daily, although some guidance can be taken from the dose of olanzapine depot that was used. Two weeks of oral therapy is recommended to establish tolerability to aripiprazole before the first depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks for all patients except those who are known to be poor cytochrome P450 2D6 metabolisers or have demonstrated sensitivity to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, changing to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

Stop haloperidol.

Patients should be initially converted to oral zuclopenthixol tablets to exclude allergy. Oral zuclopenthixol may be started while the patient still has significant haloperidol plasma concentrations from the depot. If starting oral zuclopenthixol within a week of the last haloperidol depot, the dose should be approximately 25% of the target dose.

If the patient has not had any zuclopenthixol before and oral zuclopenthixol cannot be used, a test dose of 50 mg of zuclopenthixol depot should be given 5–10 days before the zuclopenthixol depot is to be started. If there are no reactions, give the full dose of zuclopenthixol depot on the day the haloperidol depot was due.

If the patient is converting from oral zuclopenthixol to zuclopenthixol depot, the chance of allergy to the vehicle is considered low. Oral zuclopenthixol should be continued for at least 1 week after the start of treatment with zuclopenthixol depot.

The dose of haloperidol depot can be used to guide the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop haloperidol.

Patients should be initially converted to oral risperidone tablets to exclude hypersensitivity or allergy which may manifest with symptoms including angioedema, urticaria and rash. Oral risperidone may be started while the patient still has significant haloperidol plasma concentrations from the depot. If starting oral risperidone within a week of the last haloperidol depot, the dose should be approximately 25% of the target dose and titrated up according to clinical effects. Risperidone depot has a 3-week lag before significant release of risperidone from the injection site so it can be started 3 weeks before the next dose of haloperidol depot was due.

When converting from oral risperidone to risperidone depot, continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage.

Stop haloperidol.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next haloperidol depot dose was to be given. If converting the patient in this way, the loading dose regimen for paliperidone should not be used. Patients can only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for use in patients who have not been stabilised on the 4-weekly paliperidone depot for at least 4 months.

Stop haloperidol.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant haloperidol plasma concentrations. If starting oral olanzapine within a week of the last haloperidol depot, the dose should be approximately 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, it is possible to switch directly from haloperidol depot to olanzapine depot. In this case, the first olanzapine depot should be given on the day that the haloperidol depot was due.

Olanzapine is more sedating than other antipsychotic depot drugs. Because of the risk of post-injection syndrome, the patient must be observed for 2 hours after each olanzapine injection.

Stop haloperidol.

Start flupentixol on the day haloperidol depot was due.

If the patient has not had flupentixol before, there is a small chance of allergy to the drug and possibly the vehicle (coconut oil). A test dose of 5–20 mg should be given 5–10 days before the flupentixol is to be started. If there are no reactions, on the day the haloperidol depot was due, the full dose of flupentixol can be given.

The dose of haloperidol can be used to guide the target dose of flupentixol depot. Previous antipsychotic use from the patient’s history may also be helpful.

Stop haloperidol.

Convert haloperidol depot to oral aripiprazole by starting the oral aripiprazole at the target dose on the day that haloperidol depot was due. The recommended starting dose for aripiprazole is 10–20 mg daily, although some guidance can be taken from the dose of haloperidol depot that was used. Two weeks of oral therapy is recommended to establish tolerability to aripiprazole before the first depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks for all patients except those who are known to be poor cytochrome P450 2D6 metabolisers or have demonstrated sensitivity to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable length of time, a change to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

Patients should be initially converted to oral zuclopenthixol tablets to exclude allergy. Oral zuclopenthixol may be started while the patient still has significant fluphenazine plasma concentrations from the depot. If starting oral zuclopenthixol within a week of the last fluphenazine depot, the dose should be approximately 25% of the target dose.

If the patient has not had any zuclopenthixol before and oral zuclopenthixol cannot be used, a test dose of 50 mg of zuclopenthixol depot should be given 5–10 days before the full dose is to be started. If there are no reactions, give the full dose of zuclopenthixol depot on the day the fluphenazine depot was due.

If the patient is converting from oral zuclopenthixol to zuclopenthixol depot, the chance of allergy to the vehicle is considered low. Oral zuclopenthixol should be continued for at least 1 week after the start of treatment with zuclopenthixol depot.

The dose of fluphenazine depot can be used to guide the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also help.

* No longer available in Australia

Stop fluphenazine.

Patients should be initially converted to oral risperidone tablets to exclude hypersensitivity or allergy which may manifest with symptoms including angioedema, urticaria and rash. Oral risperidone may be started while the patient still has significant fluphenazine plasma concentrations from the depot. If starting oral risperidone within a week of the last fluphenazine depot, the dose should be approximately 25% of the target dose and titrated up according to clinical effects. However, risperidone depot can theoretically be started 3 weeks before the next dose of fluphenazine depot was to be given. This will ensure that risperidone depot will release significant amounts of risperidone by the time the next fluphenazine depot was to be given.

When converting from oral risperidone to risperidone depot, it is important to continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage in that period. Risperidone depot has a 3-week lag before significant release of risperidone from the injection site.

* No longer available in Australia

Stop fluphenazine.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next fluphenazine depot was due. If converting the patient in this way, the loading dose regimen for paliperidone should not be used. Patients can only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for use in patients who have not been stabilised on the 4-weekly paliperidone depot for at least 4 months.

* No longer available in Australia

Stop fluphenazine.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant fluphenazine plasma concentrations. If starting oral olanzapine within a week of the last fluphenazine depot, the dose should be approximately 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, it is possible to switch directly from fluphenazine depot to olanzapine depot. In this case, the first olanzapine depot should be given on the day that the fluphenazine depot was due.

Olanzapine is more sedating than other antipsychotic depots. Because of the risk of post-injection syndrome, the patient must be observed for 2 hours after each olanzapine injection.

* No longer available in Australia

Patients should be initially converted to oral haloperidol tablets to exclude allergy. Oral haloperidol may be started while the patient still has significant fluphenazine plasma concentrations from the depot. If starting oral haloperidol within a week of the last fluphenazine dose, give 25% of the target haloperidol dose.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions, the full dose of haloperidol depot can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of fluphenazine can be used to guide to the target dose of haloperidol depot. Previous antipsychotic use from the patient’s history may also be helpful.

* No longer available in Australia

Stop fluphenazine.

Start flupentixol on the day fluphenazine was due.

If the patient has not had flupentixol before, there is a small chance of allergy so a flupentixol test dose of 5–20 mg should be given 5–10 days before the flupentixol is to be started. If there are no reactions, give the full dose of flupentixol depot.

The dose of fluphenazine can be used to guide the target dose of flupentixol. Previous antipsychotic use from the patient’s history may also be helpful.

* No longer available in Australia

Stop fluphenazine.

Convert fluphenazine depot to oral aripiprazole by starting the oral aripiprazole at the target dose on the day that fluphenazine was due. The recommended starting dose for aripiprazole is 10–20 mg daily, although guidance can be taken from the fluphenazine that was used. Two weeks of oral therapy is recommended to establish tolerability to aripiprazole before the first depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks. Lower doses may be needed for patients who are poor cytochrome P450 2D6 metabolisers or who have been sensitive to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, a change to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

* No longer available in Australia

Stop flupentixol.

Patients should be initially converted to oral zuclopenthixol tablets to exclude allergy. Oral zuclopenthixol may be started while the patient still has significant flupentixol plasma concentrations from the depot. If starting oral zuclopenthixol within a week of the last flupentixol dose, give 25% of the zuclopenthixol target dose.

If the patient has not had any zuclopenthixol before and oral zuclopenthixol cannot be used, a test dose of 50 mg of zuclopenthixol depot should be given 5–10 days before the full dose is to be started. If there are no reactions, give the full dose of zuclopenthixol depot on the day the flupentixol depot was due.

If the patient is converting from oral zuclopenthixol to zuclopenthixol depot, oral zuclopenthixol should be continued for at least 1 week after zuclopenthixol depot is started.

The dose of flupentixol depot can be used as a guide to the target dose of zuclopenthixol depot. Previous antipsychotic use from the patient’s history may also give a guide as to the target dose of zuclopenthixol depot.

Stop flupentixol.

Patients should be initially converted to oral risperidone tablets to exclude hypersensitivity or allergy which may manifest with symptoms including angioedema, urticaria and rash. Oral risperidone may be started while the patient still has significant flupentixol plasma concentrations from the depot. If starting oral risperidone within a week of the last flupentixol dose, give 25% of the risperidone target dose.

When converting from oral risperidone to risperidone depot, continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage. Risperidone depot has a 3-week lag before significant release of risperidone from the injection site.

If converting to risperidone depot without using oral risperidone, the risperidone depot should be started 3 weeks before the next dose of flupentixol was to be given. This avoids a significant trough in antipsychotic concentrations. However, flupentixol is most commonly given every 2 weeks which creates a complicated situation. Another flupentixol dose must be given after the first risperidone dose is given because there is a risk of breakthrough symptoms before the risperidone depot starts to release.

Stop flupentixol.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next flupentixol depot was due. If converting the patient in this way, the loading dose regimen for paliperidone should not be used, unless it is necessary in a case of high clinical urgency. Patients should only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for patients who have not been stabilised on 4-weekly paliperidone depot for at least 4 months.

Stop flupentixol.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant flupentixol plasma concentrations. If starting oral olanzapine within a week of the last flupentixol dose, use 25% of the target olanzapine dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, it is possible to switch directly from flupentixol to olanzapine depot. In this case, the first olanzapine depot should be given on the day that the flupentixol dose was next due.

Olanzapine is more sedating than other antipsychotic depots. As there is a risk of post-injection syndrome, the patient must be observed for 2 hours after each injection of olanzapine depot.

Stop flupentixol.

Patients should be initially converted to oral haloperidol tablets to exclude allergy. Oral haloperidol may be started while the patient still has significant plasma concentrations of flupentixol from the depot. If starting oral haloperidol within a week of the last flupentixol dose, use 25% of the target dose.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol depot is to be started. If there are no reactions, the full dose of haloperidol depot can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

The dose of flupentixol can be used to guide the target dose of haloperidol depot. Previous antipsychotic use from the patient’s history may be helpful.

Haloperidol is regarded as having a moderate effect on QTc, while flupentixol has a low effect. QTc monitoring may be necessary when switching from flupentixol to haloperidol.

Stop flupentixol.

To switch from flupentixol to oral aripiprazole, start oral aripiprazole (10–20 mg daily) on the day that flupentixol was due. Two weeks of oral therapy is recommended to establish tolerability of aripiprazole before the first depot is administered. The recommended dose of aripiprazole depot is 400 mg every 4 weeks. Lower doses may be needed for patients who are poor cytochrome P450 2D6 metabolisers or who have been sensitive to adverse effects from aripiprazole in the past.

For patients who have used typical antipsychotics for a considerable time, a change to a partial dopamine agonist like aripiprazole carries some risk of increased agitation and irritability.

Stop aripiprazole.

Patients should be initially converted to oral zuclopenthixol tablets to establish tolerance and exclude allergy. Oral zuclopenthixol may be started while the patient still has significant aripiprazole plasma concentrations. If starting oral zuclopenthixol within a week of the last aripiprazole depot, the zuclopenthixol dose should be approximately 25% of the target dose.

Oral zuclopenthixol should be continued for at least 1 week after the start of treatment with zuclopenthixol depot.

If the patient has used zuclopenthixol before, it is possible to switch directly from aripiprazole depot to zuclopenthixol depot on the day the next aripiprazole depot was due.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of zuclopenthixol cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of zuclopenthixol.

Zuclopenthixol is significantly more sedating than aripiprazole.

Stop aripiprazole.

Patients should be initially converted to oral risperidone tablets to exclude hypersensitivity or allergy which may manifest with symptoms including angioedema, urticaria and rash. Tablets may be started while the patient still has significant aripiprazole plasma concentrations. If starting oral risperidone within a week of the last aripiprazole depot, the oral dose should be approximately 25% of the target dose. However, risperidone depot can be started 3 weeks before the next dose of aripiprazole depot was to be given. This will ensure that risperidone depot will release significant amounts of risperidone by the time the next aripiprazole depot was due.

When converting from oral to depot risperidone, continue the oral risperidone for at least 3 weeks to ensure antipsychotic coverage. Risperidone depot has a 3-week lag before significant release of risperidone from the injection site.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of risperidone cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of risperidone.

Stop aripiprazole.

If the patient has never been exposed to paliperidone (or risperidone), an oral dose should be given to test for hypersensitivity or allergy.

Paliperidone depot can be given on the day that the next aripiprazole dose was due. If converting the patient in this way, the loading dose regimen for paliperidone should not be used unless immediate efficacy is required (e.g. if the patient has had no clinical response to aripiprazole and oral treatment is not feasible). Patients should only be converted to paliperidone 4-weekly (Invega Sustenna). The paliperidone 12-weekly injection (Invega Trinza) is not suitable for patients who have not been stabilised on 4-weekly paliperidone depot for at least 4 months.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of paliperidone cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of paliperidone.

Stop aripiprazole.

Patients should be initially converted to oral olanzapine tablets to establish tolerance and exclude allergy. Oral olanzapine may be started while the patient still has significant aripiprazole plasma concentrations from the depot. If starting oral olanzapine within a week of the last aripiprazole depot, the olanzapine dose should be approximately 25% of the target dose.

Supplementation with oral olanzapine is not necessary at the start of treatment with olanzapine depot.

If the patient has used olanzapine in the past, it is possible to switch directly to olanzapine depot on the day that the aripiprazole depot was due.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of olanzapine cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of olanzapine.

Olanzapine is significantly more sedating than aripiprazole and patients may experience sedation.

Stop aripiprazole.

Patients should be initially converted to oral haloperidol tablets to exclude allergy. Tablets may be started while the patient still has significant aripiprazole plasma concentrations. If starting oral haloperidol within a week of the last aripiprazole dose, give 25% of the target haloperidol.

If switching the patient directly to haloperidol depot, give a test dose of 25 mg 5–10 days before the haloperidol is to be started. If there are no reactions, the full dose of haloperidol can be given.

If the patient is converting from oral to depot haloperidol, give an initial depot dose of 10–15 times the previous daily dose in oral haloperidol equivalents, but no more than a maximum initial dose of 100 mg (2 mL). To determine the minimum effective dose, start with lower doses and titrate upward as needed.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of haloperidol cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of haloperidol.

Stop aripiprazole and start flupentixol on the day aripiprazole was due.

If the patient has not had flupentixol before, give a test dose of 5–20 mg 5–10 days before the flupentixol is started to check for allergy. If there are no reactions, the full dose of flupentixol can be given.

Because aripiprazole is recommended as a fixed-dose depot, an equivalent dose of flupentixol cannot be estimated reliably. Previous antipsychotic use from the patient’s history may help to guide the target dose of flupentixol.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of causing QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to have more anticholinergic effects.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Paliperidone is more likely to increase prolactin.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose should be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily, unless in acute settings.

Olanzapine is likely to be more sedating and carries significantly higher risk of weight gain.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of zuclopenthixol is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

Once the clozapine dose has reached 200 mg or plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, zuclopenthixol can be reduced over 5 days or stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than zuclopenthixol.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

If the target dose of chlorpromazine is known, titrate it to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13. If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects and sedation. It also carries a higher risk of postural hypotension.

Direct switch and cross titration

Brexpiprazole has a long half-life and will take 10 to 12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg and increasing to the lower range of the target dose after 5 days.

It is advised to start brexpiprazole on day 1 but stop or reduce the zuclopenthixol dose on day 4. At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), the dose of zuclopenthixol should be reduced to 50% of the initial dose on day 4 and stopped after day 14.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (Australian product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 2 and titrate the dose as required. For bipolar disorder, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Start aripiprazole at 10 mg on day 1. If target dose is known, aripiprazole can be started at the target dose on day 1, but be aware of the risk of akathisia, insomnia and agitation at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than zuclopenthixol. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch and cross titration

At lower doses, zuclopenthixol can be stopped immediately. At higher doses (>20 mg daily), it should be reduced to 50% of the initial dose and stopped after day 7.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5. Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Do not increase the dose more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects, sedation and increase prolactin.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

Not recommended.

Cross titration

Quetiapine needs to be introduced slowly starting on day 1. The titration schedule depends on the indication. Reduce the ziprasidone dose to 50% of the original dose on day 4 and stop it on day 9.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects. Care should be taken regarding the risk of hypotension and falls.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5. Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce ziprasidone to 50% of the original dose on day 1 and stop after day 5.

Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Paliperidone is more likely to increase prolactin.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose should be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Olanzapine is likely to be more sedating and carries a higher risk of weight gain.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5. Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of ziprasidone is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

Ziprasidone carries a significant risk of QTc prolongation. Reduce the ziprasidone dose to 50% of the initial dose on day 5 of a standard clozapine initiation regimen. Once the clozapine dose has reached 200 mg or plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, ziprasidone should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than ziprasidone.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended period of reduction is recommended. Chlorpromazine should be introduced slowly to reduce the risk of hypotensive and anticholinergic adverse effects.

A suggested regimen for ziprasidone is to reduce the original dose by 50% on day 4 and stop it on day 14.

If the target dose of chlorpromazine is known, give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13. If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life and an extended period of reduction is recommended to reduce the risk of relapse.

Brexpiprazole has a long half-life and will take 10 to 12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg and increasing to the lower range of the target dose after 5 days.

It is advised to start brexpiprazole on day 1 but start the reduction in ziprasidone dose on day 4. A suggested regimen is to reduce the original ziprasidone dose by 50% on day 4 and stop it on day 14.

Direct switch

Not recommended.

Cross titration

Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5.

For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch

Not recommended.

Cross titration

Ziprasidone has a short half-life so an extended dose titration is recommended to reduce the risk of relapse. A suggested regimen is to reduce the original dose by 50% on day 1 and stop ziprasidone on day 10.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at the target dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating than ziprasidone. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch

A direct switch to amisulpride is not recommended because of the differences in effects.

Cross titration

Reduce the ziprasidone dose to 50% of the original dose on day 1 and stop after day 5.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause sedation.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on the clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch

Paliperidone is the main metabolite of risperidone and has a similar adverse-effect profile. A direct switch is recommended. Risperidone should be stopped on day 1 and paliperidone should be started on day 1 at the target dose.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Cross titration

This is not recommended as paliperidone is the active metabolite of risperidone and will be present at some level already.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose may be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Olanzapine is likely to be more sedating and cause more weight gain.

A slower cross titration and higher treatment doses may be necessary in some high-risk patients, especially in community settings.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of risperidone is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg)

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, risperidone should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than risperidone.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects and sedation. It also carries a higher risk of postural hypotension.

Direct switch and cross titration

Brexpiprazole has a long half-life and will take 10 to 12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg and increasing to the lower range of the target dose after 5 days. It is advised to start brexpiprazole on day 1 but stop or reduce the risperidone dose on day 4. If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 4 and then stopped at day 10.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 2 and titrate the dose as required. For bipolar depression, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped on day 5.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than risperidone. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch and cross titration

If risperidone was prescribed in doses above 3 mg daily, the dose should be reduced to 50% on day 1 and then stopped at day 5.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Do not increase the dose more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch and cross titration

Although quetiapine is sedating and carries some risk of cholinergic rebound, periciazine has some similar effects so an extended withdrawal regimen is not necessary. For moderate to higher doses (above approximately 300 mg) of quetiapine, reduce the dose to 50% on day 1 and stop it on day 5.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch and cross titration

Although quetiapine is sedating and carries some risk of cholinergic rebound, olanzapine has similar effects. Therefore, an extended withdrawal regimen is not necessary. It is suggested that moderate to higher doses (above approximately 300 mg) of quetiapine be withdrawn by reducing the dose to 50% on day 1 and stopping it on day 5.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose should be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments or decrements of 5 mg daily are recommended, unless in acute settings.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses of up to 160 mg a day may be required. Lurasidone should be taken with food.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of quetiapine is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Quetiapine is sedating and carries a moderate risk of QTc prolongation. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose down from day 5 of a standard clozapine initiation regimen (from 12.5 mg or 25 mg).

Once the clozapine dose has reached 200 mg or plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, quetiapine should be stopped.

Clozapine will cause significantly more postural hypotension and dizziness, tachycardia, hypersalivation and constipation than quetiapine. The sedative effects of clozapine may be increased by quetiapine.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly. However, because of the similarity in sedation and blood pressure effects, there are lower risks of a faster change to chlorpromazine.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Even though quetiapine does have some anticholinergic, sedative and hypotensive effects, chlorpromazine is more likely to cause anticholinergic adverse effects and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg and increasing to the lower range of the target dose after 5 days. It is advised to start brexpiprazole on day 1 when the reduction in quetiapine dose is first made.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 2 and titrate the dose as required. For bipolar depression, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly. A slow reduction in dose is not usually required for low-dose quetiapine.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at the target dose on day 1, although akathisia, insomnia and activation are more likely to occur at higher doses. It is ideal to wait 14 days between dose adjustments.

Aripiprazole is likely to be more activating or at least less sedating than quetiapine. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole. Aripiprazole has no anticholinergic effects so there is some risk of cholinergic rebound after stopping quetiapine.

Direct switch and cross titration

Quetiapine is sedating and can have anticholinergic effects. If moderate to higher doses (above approximately 300 mg) of quetiapine are initially prescribed, titrate the dose slowly.

For immediate-release quetiapine, give 75% of the original dose on days 1–4, 50% on days 5–8, 25% on days 9–12, and stop quetiapine on day 13.

For extended-release quetiapine, give 50% of the original dose on days 1–7 and stop quetiapine on day 8.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 5 days.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine may be more sedating and may have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life.

Although olanzapine does have some anticholinergic activity, an extended period of reduction of high-dose periciazine is still recommended to reduce the risk of relapse or cholinergic rebound. Low-dose periciazine may be stopped immediately.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose may be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Direct switch and cross titration

High doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch and cross titration

Higher doses (>30 mg daily) of periciazine should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of periciazine is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

If high doses (>30 mg daily) of periciazine have been used, the dose should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, periciazine should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than periciazine. Periciazine does have some sedative and anticholinergic effects and these may increase the adverse effects of clozapine.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life. As the spectrum of adverse effects tends to be similar to chlorpromazine, a faster reduction of periciazine can be used.

If the target dose of chlorpromazine is known, titrate the dose slowly to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is to give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Even though the adverse-effect profile of periciazine is similar to chlorpromazine, chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension and falls.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 2 and titrate the dose as required. For bipolar depression, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch

Because of the differences in adverse effects profiles and half-lives a direct switch is not recommended.

Cross titration

Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life. An extended period of reduction is recommended to reduce the risk of relapse or cholinergic rebound.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg and increasing to the lower range of the target dose after 5 days.

It is advised to start brexpiprazole on day 1 but stop or reduce the periciazine dose on day 4. Higher doses of periciazine (>30 mg daily) should be reduced by 50% and then stopped after approximately 10 days.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch and cross titration

Higher doses of periciazine (>30 mg daily) should be reduced by 50% on day 1 and then stopped after approximately 10 days. Periciazine is a low-to-medium-potency, typical antipsychotic with a short half-life, so an extended period of reduction is recommended because of the risk of relapse or cholinergic rebound.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than periciazine. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole. Aripiprazole has no anticholinergic effects so there is a small risk of cholinergic rebound after stopping periciazine.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone is poorly absorbed if not taken with food. It has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to have sedative effects.

Direct switch

As paliperidone is the active metabolite of risperidone and the two drugs have similar affinities for neurotransmitter receptors, a direct switch is recommended. Stop paliperidone on day 1 and start the equivalent dose of risperidone on day 1.

Cross titration

There is little added value to cross titrating from risperidone to paliperidone since there will always be some level of paliperidone present from the metabolism of risperidone.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects.

Care should be taken with initial cross titration because of postural hypotension and risk of falls.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours at increments or decrements of 5 mg daily.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects and sedation. It also carries a higher risk of postural hypotension.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of paliperidone is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

If higher doses of paliperidone have been used, the dose should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, paliperidone should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than paliperidone.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Brexpiprazole has a long half-life and will take 10 to 12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. It is advised to start brexpiprazole on day 1, when the paliperidone dose is first reduced.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 2 and titrate the dose as required. For bipolar depression, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

Paliperidone can be stopped on day 1. It has a half-life of 23 hours and will wash out in about 5 days.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to the target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Direct switch and cross titration

Low doses of paliperidone can be stopped on day 1. Higher doses (>6 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but risks greater akathisia, agitation and insomnia. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating than paliperidone. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and may have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of olanzapine is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

If higher doses of olanzapine have been used, the dose should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, olanzapine should be stopped.

Clozapine will cause significantly more postural hypotension and dizziness, tachycardia, hypersalivation and constipation than olanzapine. Sedative effects of olanzapine and clozapine are likely to be additive.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. It is advised to start brexpiprazole on day 1, when the olanzapine dose is reduced.

Brexpiprazole is likely to be less sedating than olanzapine and carries less risk of weight gain. There is some risk of cholinergic rebound when olanzapine is withdrawn.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

If the target dose of chlorpromazine is known, titrate the dose slowly to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is to give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

Low doses of olanzapine can be stopped on day 1. Higher doses (>10 mg) should be reduced by 50% on day 1 and stopped after 7 days.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than olanzapine. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole. Aripiprazole has no anticholinergic effects so there is some risk of cholinergic rebound after stopping olanzapine.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly. Because of the differences in adverse-effect profiles a direct switch is not recommended.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and will have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of lurasidone is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

The dose of lurasidone should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, lurasidone should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than lurasidone.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

Direct switch

Because of the differences in adverse effects profiles, a direct switch to chlorpromazine is not recommended.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

If the target dose of chlorpromazine is known, titrate the dose slowly to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is to give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch

Starting brexpiprazole according to the manufacturer’s recommendations will take some time to reach effective plasma concentrations so a direct switch is not recommended.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. It is advised to start brexpiprazole on day 1, when the lurasidone dose is first reduced.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 5.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

As initial dose titration is not required, it is likely there will be few adverse effects on stopping lurasidone. The risk of breakthrough symptoms should be considered if stopping abruptly.

Cross titration

Reduce the lurasidone dose by 50% on day 1 and stop on day 7.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to have sedative effects.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and will have more anticholinergic effects.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titrate gradually in view of the risk of first-dose postural hypotension. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 mg or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day, administered as a single daily dose. The dose may be adjusted based on individual clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments/decrements of 5 mg daily are recommended unless in an acute setting.

Olanzapine is more likely to cause sedation and weight gain.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

If the target dose of chlorpromazine is known, titrate the dose slowly to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is to give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and postural hypotension.

Direct switch and cross titration

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of haloperidol is likely to leave an extended period when the patient has no effective antipsychotic cover.

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

If higher doses (>5 mg daily) of haloperidol have been used, the dose should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, haloperidol should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than haloperidol.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, asenapine should be started at 10 mg twice a day and, if necessary, the dose can be reduced.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. It is advised to start brexpiprazole on day 1, when the haloperidol dose is reduced.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating than haloperidol. There is a risk of akathisia, developing and some chance of agitation and irritability with the change to aripiprazole.

Direct switch and cross titration

At lower doses (less than 5 mg daily), haloperidol can be stopped immediately. At higher doses, it should be reduced to 50% of the initial dose and stopped after day 7.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 25% of the target dose on day 1 and increased by 25% of the target dose every week. If the target dose is not known, it is recommended to start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3 but, because of the slow withdrawal of clozapine, weekly dose adjustments are recommended.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. As clozapine has significant anticholinergic and sedative effects, the need to slowly introduce quetiapine is reduced. If clozapine is stopped abruptly, quetiapine can be started at 50% of the target dose on day 1 and increased, if necessary, to the target dose on day 5.

If the clozapine dose is slowly titrated down, quetiapine can be introduced on day 1 at a lower dose and an increasing regimen that matches the clozapine regimen can be used to increase the quetiapine dose.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Risperidone may be started at an initial dose of 1 mg daily on day 1. In some patients a slower titration phase and lower starting and maintenance dose may be appropriate. Titration should be gradual because of the risk of extrapyramidal effects after the lack of dopamine effects from clozapine. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. Start brexpiprazole at 1 mg daily on day 3 of the clozapine reduction regimen.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

If the target dose of chlorpromazine is known, a suggested regimen is to give 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to increase prolactin. Clozapine and chlorpromazine are both heavily sedating, cause anticholinergic effects and carry a high risk of postural hypotension. These effects will be additive, so addition of chlorpromazine to a very slow wean of clozapine should be done cautiously.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Patients who have been on clozapine will have experienced no significant dopamine blockade for some time. It is therefore advised that the slowest titration of haloperidol is used. The usual suggestion is to start haloperidol at 50% of the target dose on day 1 and increase to the target dose on day 5. This may be too aggressive and cause significant adverse effects so be guided by effects experienced by the patient. Some patients may require a slower titration e.g. over 2 weeks or longer.

Haloperidol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than clozapine. There is a risk of akathisia, agitation and irritability with the change to aripiprazole. Aripiprazole has no anticholinergic effects so there is some risk of cholinergic rebound after stopping clozapine.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

If clozapine is stopped abruptly, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. If clozapine is to be washed out slowly, start asenapine at 5 mg twice a day at around day 7 of the reduction regimen.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Zuclopenthixol has few anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch

Not recommended.

Cross titration

Always consult a psychiatrist when discontinuing clozapine. Abrupt cessation of clozapine carries a high risk of rebound psychosis and rebound anticholinergic symptoms. If rebound psychosis occurs, it can be severe and accompanied by physical and autonomic symptoms that resemble neuroleptic malignant syndrome. In severe cases, sometimes the only option is to restart clozapine. If this is not feasible because of adverse effects such as severe neutropenia, myocarditis or cardiomyopathy, specialist consultation is advised.

If possible, clozapine should be stopped very slowly over 6 weeks. Very high-risk patients should stop clozapine over 3–6 months.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Ziprasidone has few anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose based on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Risperidone has no anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended for adults. In some patients a slower titration phase and lower risperidone starting and maintenance dose may be appropriate. Postural hypotension can occur with the first dose. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Chlorpromazine does have higher anticholinergic and hypotensive effects than quetiapine, but the risk of cholinergic rebound is less when switching to quetiapine compared to some other antipsychotics.

Reducing the chlorpromazine dose can be relatively fast when switching to quetiapine. A suggested regimen is to give 75% of the original dose on days 1–4, 50% on days 5–8, then stop chlorpromazine on day 9.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Paliperidone has no anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Haloperidol has minimal anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and carries a higher risk of increasing prolactin.

A slower cross titration may be necessary in some very high-risk patients, especially in community settings.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Lurasidone has no anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Brexpiprazole has no anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Start brexpiprazole at 1 mg daily on day 3 of the suggested chlorpromazine reduction regimen. Brexpiprazole has a long half-life and will take 10 to 12 days to reach steady-state concentrations. In addition, the manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. This results in a very slow introduction, therefore it is advised to start brexpiprazole 10 days before the planned washout of chlorpromazine.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of chlorpromazine is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg). As chlorpromazine has significant adverse effects that are also seen with clozapine, it is recommended to reduce the chlorpromazine dose earlier rather than later. Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, chlorpromazine should be stopped.

The combination of chlorpromazine and clozapine carries a high risk of increased postural hypotension, tachycardia, constipation and reduction of the seizure threshold. QTc should also be monitored as chlorpromazine has a moderate effect on QTc.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Start aripiprazole at 10 mg on day 1. If the target dose is known, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than chlorpromazine. There is a risk of akathisia, agitation and irritability with the drug change. Aripiprazole has no anticholinergic effects so there is some risk of cholinergic rebound after stopping it.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Asenapine has minimal anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine.

Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Asenapine can be started on day 5. For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, start asenapine at 10 mg twice a day and reduce the dose if necessary.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine should be slowly stopped to avoid cholinergic rebound, possible blood pressure effects and behavioural effects related to loss of sedation.

Cross titration

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride has no anticholinergic effects so there is some risk of cholinergic rebound after stopping chlorpromazine. Reduce the chlorpromazine dose slowly so it is low enough to stop by day 14. A suggested regimen is to give 75% of the chlorpromazine dose on days 1–4, 50% on days 5–8, 25% on days 9–12, then stop chlorpromazine on day 13.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce ziprasidone or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, it is recommended to start ziprasidone at 40 mg twice daily and adjust the dose depending on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce zuclopenthixol or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce risperidone or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended for adults. In some patients a slower titration phase and lower risperidone starting and maintenance dose may be appropriate. Postural hypotension can occur with the first dose. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce quetiapine or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce periciazine or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce olanzapine or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Olanzapine will be more sedating than brexpiprazole and is likely to cause significantly more weight gain.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce paliperidone or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Paliperidone is more likely to increase prolactin.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce lurasidone or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce haloperidol or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and increase prolactin. It is also likely to have some dysphoric effect, particularly after the use of partial dopamine agonists.

Direct switch or cross titration

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of brexpiprazole is likely to leave an extended period when the patient has no effective antipsychotic cover.

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, brexpiprazole can be stopped. The long half-life of brexpiprazole means rebound effects are unlikely.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce asenapine or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Asenapine can be started on day 2. For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required.

Expect asenapine to be more sedating than brexpiprazole and more likely to cause postural hypotension. The incidence of nausea and weight gain is higher than with brexpiprazole.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce chlorpromazine or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% of the target dose on days 5–8, 75% of the target dose on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce aripiprazole or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Start aripiprazole at 10 mg on day 1. If the target dose is known from the patient’s previous response to aripiprazole, it can be started at that dose on day 1. Consider dose increase, if necessary, after 14 days.

Aripiprazole is more likely to cause akathisia.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose based on clinical effects. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch or cross titration

Brexpiprazole can be stopped on day 1 whether the intention is to slowly introduce amisulpride or to start it at the target dose. The long half-life of brexpiprazole means rebound effects are unlikely.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

A direct switch carries more risk of emergent symptoms than a cross titration. The recommended starting dose of ziprasidone is 40 mg twice daily and this dose may need to be adjusted up.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, it is recommended to start ziprasidone at 40 mg twice daily and adjust the dose depending on clinical effects. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended for adults. In some patients a slower titration phase and lower risperidone starting and maintenance dose may be appropriate. Postural hypotension can occur with the first dose. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects than asenapine.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating and is likely to have more anticholinergic effects.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Olanzapine is likely to cause more sedation and more anticholinergic effects. A more gradual change is recommended.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Olanzapine may be more sedating than asenapine and is likely to cause significantly more weight gain.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch

Stop asenapine on day 1 and start lurasidone. Lurasidone is more likely to cause extrapyramidal effects than asenapine.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Haloperidol is far more likely to cause extrapyramidal effects. It is recommended the slower introduction is used for haloperidol.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is more likely to cause extrapyramidal effects and increase prolactin.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of asenapine is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg).

If higher doses of asenapine have been used, the dose of asenapine should be reduced to 50% on day 7 of a standard clozapine initiation regimen.

Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, asenapine can be stopped. As clozapine will be in or close to the therapeutic range, any rebound from the cessation from asenapine is unlikely. If in the initial titration of clozapine the patient experiences significant postural hypotension or sedation, asenapine can be reduced earlier. In this case, reduce the asenapine dose by 50% and further reduction or cessation should be guided by adverse effects.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs. Chlorpromazine is more likely to cause postural hypotension and to have strong anticholinergic and sedative effects.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Chlorpromazine is more likely to cause anticholinergic adverse effects, sedation and increase prolactin. It also carries a higher risk of postural hypotension.

Direct switch

A direct switch is not recommended because of the differences in half-lives.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at a low dose and taking 5 days before the lower range of the target dose is reached. Start brexpiprazole on day 1, when the asenapine dose is reduced to 50%.

Direct switch

A direct switch is not recommended because of the differences in adverse-effect profiles of the two drugs.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

A direct switch is not recommended as aripiprazole has a long half-life and takes 14 days to reach steady-state plasma concentrations. It is safer in terms of risk of relapse to use a cross titration.

Cross titration

Reduce the dose of asenapine to 50% on day 1 and stop on day 5.

Start aripiprazole at 10 mg on day 1. If the target dose is known from the patient’s previous response, aripiprazole can be started at that dose on day 1, but be aware of the risk of akathisia, agitation and insomnia at higher doses. Consider dose increase after 14 days.

Aripiprazole is likely to be more activating or at least less sedating than asenapine. There is a risk of akathisia developing, and some chance of agitation and irritability, with the change to aripiprazole.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose depending on clinical effect. Increases in dose should not be made more frequently than every 5 days.

Zuclopenthixol is more likely to cause sedation, dystonia and tremors than aripiprazole.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly. If cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended for adults. In some patients a slower titration phase and lower risperidone starting and maintenance dose may be appropriate. Postural hypotension can occur with the first dose. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly. If cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Ziprasidone is poorly absorbed if not taken with food.

Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start ziprasidone at 40 mg twice daily and adjust the dose depending on clinical effect. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Periciazine is likely to be more sedating and have more anticholinergic effects.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine is more sedating and is likely to have more anticholinergic effects than aripiprazole.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Start lurasidone at 40 mg once daily on day 1. Initial dose titration is not required and optimal clinical response and tolerability for most patients is expected to be 40 or 80 mg once daily. Doses up to 160 mg a day may be needed. Lurasidone should be taken with food.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Olanzapine should be started at night on day 1. For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Olanzapine will be more sedating and have anticholinergic effects in the short term.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.

Haloperidol is much more likely to cause tremor and dystonia than aripiprazole. It is also likely to have a dysphoric effect, particularly after treatment with aripiprazole.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

If the target dose of chlorpromazine is known, titrate the dose to reduce the anticholinergic and hypotensive adverse effects. A suggested regimen is giving 25% of the target dose on days 1–4, 50% on days 5–8, 75% on days 9–12, then the target dose on day 13.

If the target dose is not known, be guided by the patient’s previous medication history to estimate the chlorpromazine dose.

Direct switch

A direct switch is not recommended as clozapine is slowly titrated from 12.5 mg (or 25 mg) and cessation of aripiprazole is likely to leave an extended period when the patient has no effective antipsychotic cover.

Cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly. If cross titration is desired or if higher doses have been used, the dose may be reduced to 50% on day 7.

Start clozapine according to standard titration schedules (from 12.5 mg or 25 mg). Once the clozapine dose has reached 200 mg or clozapine plasma concentrations have reached 350 microgram/L, and the patient has shown significant clinical effect, aripiprazole should be stopped.

Clozapine will cause significantly more sedation, postural hypotension and dizziness, tachycardia, hypersalivation and constipation than aripiprazole.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Asenapine has a terminal elimination half-life of about 24 hours and steady state is reached within 5 days (Australian product information states 3 days).

For schizophrenia, start asenapine at 5 mg twice a day on day 1 and titrate the dose as required. For bipolar disorder, start asenapine at 10 mg twice a day. If necessary, the dose can be reduced.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Brexpiprazole has a long half-life and will take 10–12 days to reach steady-state concentrations. The manufacturer recommends starting brexpiprazole at 1 mg daily and titrating up. This can be started on the day that aripiprazole is stopped.

Direct switch

Zuclopenthixol is significantly more sedating and may have more anticholinergic effects than amisulpride. Cross titration is regarded as a safer method of changing antipsychotics.

Cross titration

Zuclopenthixol is significantly more sedating than amisulpride.

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Zuclopenthixol may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, start zuclopenthixol at 20 mg daily and adjust the dose depending on clinical effect. Increases in dose should not be made more frequently than every 5 days.

Direct switch or cross titration

As the half-life of aripiprazole is long (approximately 75 hours), there is less need to slowly reduce the dose when switching to another antipsychotic. Aripiprazole may be stopped abruptly or, if cross titration is desired, the dose may be reduced to 50% for 14 days and then stopped.

Start amisulpride on day 1. It will take approximately 3 days to reach steady-state plasma concentrations. The product information recommends starting at the target dose, but in clinical practice start at 200 mg to avoid acute dystonia and increase to target dose. For positive symptoms of psychosis, the target dose is 200–800 mg daily.

Amisulpride is more likely to increase prolactin and cause sexual dysfunction.

Direct switch

Amisulpride and ziprasidone have similar half-lives and the maximum recommended dose of ziprasidone can be reached as early as day 3 of treatment. Because of the cardiac risks, baseline electrolytes and ECG are recommended.

Cross titration

Ziprasidone is poorly absorbed if not taken with food.

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Ziprasidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is not known, it is recommended to start ziprasidone at 40 mg twice daily and adjust the dose depending on clinical effect. The dose may be increased as early as day 3.

Ziprasidone has a higher risk of QTc prolongation, therefore baseline serum magnesium, potassium and an ECG should be taken.

Direct switch

Quetiapine is significantly more sedating than amisulpride. It also has significantly less dopamine effects so that any extrapyramidal effects should resolve and increased prolactin should reduce. A direct switch is not recommended but, if performed, the risk of side effects from the changeover is increased.

Cross titration

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5.

For bipolar depression, immediate- or modified-release quetiapine should be administered once daily at bedtime and titrated from a low dose. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

The dose may be adjusted up to 600 mg/day in increments of 100 mg/day depending on clinical response and tolerability.

For acute mania, immediate-release quetiapine should be administered twice daily. A recommended regimen to introduce quetiapine is:

• 100 mg on day 1
• 200 mg on day 2
• 300 mg on day 3
• 400 mg on day 4.

It can be used alone or in combination with a mood stabiliser. Further dosage adjustments up to 800 mg/day by day 6, should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response and tolerability to 200–800 mg/day. The usual effective dose is 400–800 mg/day.

For schizophrenia, immediate-release quetiapine should be administered twice daily and modified-release should be administered once daily. A suggested regimen is:

• 50 mg on day 1
• 100 mg on day 2
• 200 mg on day 3
• 300 mg on day 4.

From day 4, the dose should be titrated to the usual effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted to 150–750 mg/day.

Quetiapine will be more sedating than amisulpride and is likely to have more anticholinergic effects.

Care should be taken with initial cross titration in relation to postural hypotension and risk of falls.

Direct switch

Patients may experience some postural hypotension on switching. Risperidone also carries a higher risk of sedation than amisulpride.

Cross titration

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Risperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5. If the target dose is unknown, an initial dose of 1 mg daily is recommended for adults.

In some patients a slower titration phase and lower risperidone starting and maintenance dose may be appropriate. Postural hypotension can occur with the first dose. Risperidone can be given once or twice daily.

Risperidone is more likely to increase prolactin.

Direct switch

Periciazine is likely to be more sedating and may have more anticholinergic effects than amisulpride. There is also a higher risk of postural hypotension with periciazine.

Cross titration

Periciazine is likely to be more sedating and have more anticholinergic effects than amisulpride.

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Periciazine may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch

The patient should be advised to take paliperidone at the same time in relation to food and should not be concerned if they occasionally notice something in their stools that looks like a tablet.

Cross titration

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Paliperidone may be started at 50% of the target dose on day 1 and increased, if necessary, on day 5.

Direct switch

Olanzapine is significantly more sedating and may have more anticholinergic effects than amisulpride. There is also a higher risk of postural hypotension with olanzapine.

Cross titration

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Olanzapine may be started at 50% of the target dose on day 1 (at night) and increased, if necessary, on day 5.

For schizophrenia and related disorders, start at 5–10 mg/day as a single daily dose. The dose may be adjusted based on clinical response and adverse effects.

For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg once a day as monotherapy, or 10 mg once daily in combination with lithium or valproate. If indicated, dose adjustments should generally occur at intervals of not less than 24 hours and in increments or decrements of 5 mg daily.

Direct switch

Haloperidol has a significantly higher risk of extrapyramidal effects than amisulpride, particularly when amisulpride is used at low doses e.g. below 200 mg daily.

Cross titration

Amisulpride should be reduced to 50% of the dose on day 1 and stopped at day 5. Haloperidol should be started at 50% of the target dose on day 1 and increased to the target dose on day 5.