Acute management of bipolar disorders

Acute bipolar presentations include manic, hypomanic, mixed, and depressive states. Manic presentations cannot be contained in a primary care setting and require psychiatric assessment for hospitalisation. Several drugs that have mood stabilising actions are now available, providing more treatment options for clinicians. Antidepressant use in bipolar depression remains controversial, but if considered clinically appropriate must be administered with a drug that stabilises mood. Psychosocial interventions help patients with recovery and to cope with residual symptoms of illness.

Patients with bipolar disorders face significant risks of morbidity and mortality and present medical practitioners with considerable diagnostic and management challenges. The lifetime prevalence of bipolar disorders is estimated at 1-4% of the general population.¹Suicide is attempted by 25-50% of sufferers², and overall 15% of people with bipolar disorders die by suicide.³

Accurate diagnosis depends on recognising often under-reported symptoms of elevated mood. Mixed states (combined depressive and elevated symptoms) and comorbid substance misuse frequently cloud the initial diagnosis. These diagnostic complexities along with often impaired patient insight lead to a third of Australian patients suffering illness for more than ten years before accurate diagnosis is made and appropriate treatment given.⁴

These are characterised by episodic depressions and elevations of mood. Bipolar I involves manic symptoms which last for at least a week and are severe enough to markedly impair functioning or require hospitalisation. In contrast, bipolar II involves hypomania in which elevated symptoms are less severe but still clearly different from usual mood and last for at least four days. In both forms of the illness, depressive episodes tend to be more frequent and disabling than mania. Sufferers spend 32-50% of follow-up in depressive episodes and only 1-9% in elevated states.⁵Most patients have inter-episode periods of recovery, but over 90% relapse without medications.⁶

It is necessary to determine the most appropriate settings for patient care, and assess for suicidal ideations by examining past history of self-harm, current ideation, substance abuse, and the level of social supports.

In elevated and mixed states, the possibility of risk taking, impulsive behaviours, irritability, violence and misadventure must be considered. Where risks are deemed high, the patient needs more assertive care, and referral to psychiatric inpatient services is appropriate. Application of the relevant state mental health act may be required. Manic episodes cannot be contained in a general practice or community setting.

Given the diagnostic and management challenges of bipolar disorder, psychiatric confirmation of diagnosis and management advice is advisable. For patients with low to moderate risk, their initial care will usually be provided by their general practitioner, who has a pivotal role in assessment, diagnosis, referral and ongoing care.

The goal of treatment in bipolar disorder is to stabilise mood. Symptomatic and specific maintenance medications are available for the acute treatment of bipolar disorders. However, maintenance medication remains the cornerstone of management - both for acute episodes and maintenance treatment.⁷

In recent years several new drugs have shown efficacy for the control of manic symptoms and prevention of relapse, but not all are approved for use in bipolar disorders.⁸Trialling medications in the acute phase of the illness - depressed, mixed, hypomanic and manic episodes - helps to find the most effective and tolerable drug or drugs necessary to achieve and maintain euthymic mood in individual patients.

In Australia, several effective drugs for bipolar disorders are subsidised by the Pharmaceutical Benefits Scheme, but some drugs require private prescriptions for use (see Table 1).

Table 1 Drugs for the acute management of manic episodes First-line - lithium - valproate - carbamazepine - second generation antipsychotics (olanzapine*, risperidone, quetiapine, aripiprazole*, ziprasidone*) Second-line - second generation antipsychotic plus lithium or valproate - lithium plus valproate Third-line - electroconvulsive therapy - clozapine† This list is a composite of recent evidence-based reviews and consensus management guidelines for bipolar mania.8,9 * indicates no Pharmaceutical Benefits Scheme subsidy for acute mania at time of writing † the efficacy of clozapine is decreased with smoking

Manic episodes

Drugs recommended for the treatment of manic episodes are listed in Table 1.⁸,⁹Lithium, certain anticonvulsants¹⁰and several antipsychotics have mood stabilising properties. They treat and prevent mood elevations and, to a lesser extent, help control and prevent depressive episodes.

Episodes of mania typically require inpatient management. Patients with mania require sedation to reduce psychomotor acceleration. So called 'manic exhaustion' had a very high mortality in the premedication era. Prompt restoration of the sleep-wake cycle assists recovery. Often adjunctive benzodiazepines are used for sedation, but it is preferable if the drug chosen to stabilise mood can also serve this function. Managing mania sometimes requires large doses of antimanic drugs in the acute phase, though lower doses may suffice in the maintenance phase. Tolerability is a key factor for subsequent compliance with medications and long-term illness control.

Resolution of the acute episode takes weeks to months. Approximately 50% of patients with mania will respond to monotherapy with any antimanic drug, and around 70-75% will respond to combination therapy. The longer-term evidence on such combination therapy remains limited, and while monotherapy is preferable from compliance, tolerability and cost perspectives, only a third of patients achieve longer-term mood stability on monotherapy.¹¹Combination therapy is pragmatically the norm. In rare treatment-resistant cases of mania, where even multiple medications fail to control mania, electroconvulsive therapy and in some cases clozapine may need to be trialled.¹²Acute treatment is generally the start of maintenance therapy.

Hypomanic episodes

Due to the shorter duration of hypomanic episodes, and the lack of marked impairment, hypomania is less frequently the presenting symptom of the illness. Patients with hypomania may feel energetic and creative, and may not need much sleep. They are unlikely to present complaining of feeling 'too well'.

In clinical practice, treatments for manic states are effective in hypomania. Importantly, patients with only hypomanic but no manic episodes (bipolar II pattern) do not tend to progress to bipolar I manic states. Nonetheless, hypomanic episodes are a core precipitant of downward mood destabilisations into major depressive episodes, and thus warrant active treatment, even though depression is invariably the reason patients present for treatment in bipolar II disorder.

Mixed episodes

Mixed states are characterised by elevated and depressed mood mixed together and are among the most difficult mood conditions to identify. Elevated symptoms can be brief, and include racing and 'crowded' thoughts, lability of affect, insomnia and restlessness. Specific pharmacotherapy for mixed states is extrapolated from treatments for mania. One crucial factor is to avoid antidepressants during such mixed states, as they will exacerbate and sometimes trigger the episodes. This can be counterintuitive, when patients present with a dysphoric affect. Mixed states are the most under-recognised of the bipolar specific states, and it is likely that many mixed states are triggered by antidepressants. If a patient's agitated depressive symptoms seem to worsen with antidepressants, consider the possibility of a mixed state and bipolar diagnosis.

Depressive episodes

Drugs for the treatment of bipolar depressive episodes are listed in Table 2.^8,9 The best current evidence for efficacy in bipolar depression exists for lithium, quetiapine and lamotrigine.⁸

Antidepressants place patients at risk of switching to elevated phases of the disorder and rapid cycling patterns. Although the results of a recent study do not support the use of adjunctive antidepressant therapy in the acute treatment of bipolar depression¹³, this topic remains very controversial. Many patients with bipolar depression will not respond to changes in mood stabilising medicines alone. They may need an antidepressant, but this must be taken with a mood stabilising drug. Frequent regular mental state review is necessary for any patient taking this combination to detect destabilisation, and non-response or loss of response to the antidepressant. Patients should not simply be left on the antidepressant long term without review.

Considerable controversy exists as to how long antidepressants should be continued, and there is no good evidence of efficacy in the maintenance phase. What is clear is the need for monitoring of the patient's mental state and dose reduction or cessation of the antidepressant if elevated symptoms emerge.

Should an antidepressant be needed, low-dose selective serotonin reuptake inhibitors are usually adequate and may have less propensity to induce elevated phases of the disorder.¹⁴As fluoxetine has a five-week washout period it is best avoided in bipolar conditions in case a manic, mixed or hypomanic mood switch necessitates cessation.

Table 2 Drugs for acute management of bipolar depressive episode Optimise current medications or initiate therapy First-line - lithium, quetiapine or lamotrigine monotherapy - lithium or valproate with selective serotonin reuptake inhibitor or bupropion* - olanzapine with selective serotonin reuptake inhibitor - lithium with valproate Second-line - add-on or switch to a second mood stabiliser† and/or add a selective serotonin reuptake inhibitor (if patient is not already taking one) Third-line - mood stabiliser† with serotonin noradrenaline reuptake inhibitor or tricyclic antidepressant or monoamine oxidase inhibitor - electroconvulsive therapy This list is a composite of recent evidence-based reviews and local consensus management guidelines for bipolar depression.8,9 * an antidepressant re-patented in Australia for smoking cessation †lithium, valproate, carbamazepine, lamotrigine, olanzapine or quetiapine. Keep patient on whichever mood stabilising drugs have worked during elevated phases of illness.

Education, self-monitoring of mood, mood diaries and social rhythm training all assist with better longer-term patient outcomes. Psychosocial care is best implemented as early as possible in the course of illness to help patients with recovery and to cope with residual symptoms of illness. Including family and carers in the management plan is an important aspect of care. Continuity of care with good communication and rapport between doctor and patient is particularly important in fostering compliance with treatment and earlier presentation for acute care in the event of relapse.

Bipolar disorders can present in varying ways. Prompt recognition of the phase of illness and tailoring the patient's therapy accordingly will help optimise outcomes. Consider bipolar disorders in patients with treatment-resistant or recurrent depression. Newer anticonvulsants and antipsychotics offer further treatment options for these diverse and often disabling illnesses. Prescribers should carefully monitor patients with bipolar disorders who require antidepressants, given the risk of destabilising their mood. Integrating education, lifestyle modification and engagement of patients and carers in management augments therapeutic efficacy.

The following statements are either true or false.

1. Patients with mania are best managed in general practice.
2. In bipolar disorders, patients taking a mood stabilising drug combined with an antidepressant should be regularly reviewed for changes in their mental state.

Answers to self-help questions

1. False

2. True