Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Abilify (Bristol-Myers Squibb)

10 mg, 15 mg, 20 mg and 30 mg tablets

Approved indication: schizophrenia

Australian Medicines Handbook section 18.2.2

Aripiprazole is a new atypical antipsychotic. These drugs are less likely to cause extra pyramidal adverse effects than typical antipsychotics such as haloperidol.

As aripiprazole is a partial agonist at dopamine (D2) receptors it may increase neurotransmission if the concentration of dopamine is low and decrease neurotransmission if the dopamine concentration is high. This action may have effects on the positive and negative symptoms of schizophrenia. Aripiprazole is also a partial agonist at serotonin (5HT1A) receptors, but an antagonist of 5HT2A receptors.

The drug only needs to be taken once a day. After absorption, aripiprazole is converted to an active metabolite. As aripiprazole and its metabolite have long half-lives steady-state plasma concentrations are not reached for approximately two weeks. Dose increases should therefore be at least two weeks apart.

The metabolism of aripiprazole involves cytochrome P450 2D6 and 3A4. This increases the potential for interactions with drugs such as fluoxetine, paroxetine and carbamazepine. Most of the unchanged drug and its metabolites are excreted in the faeces.

The clinical trials of aripiprazole have used rating scales such as the Positive and Negative Syndrome Scale (PANSS) to assess the drug's efficacy. In most short-term studies (4-6 weeks) aripiprazole has had a greater effect than placebo on this scale. One of the trials included haloperidol as an active control. Although haloperidol and aripiprazole reduced the PANSS scores significantly more than placebo, the study was not designed to show a difference between the active treatments.1

In clinical trials common adverse events included headache, nausea, anxiety and insomnia. Compared to haloperidol, aripiprazole caused less somnolence and extra pyramidal effects, but more nausea and dizziness.1As aripiprazole acts as an antagonist at a1 adrenergic receptors it may cause orthostatic hypotension, so it should be used cautiously in patients with cardiovascular disease. Patients may gain weight during long-term treatment. As with other antipsychotics, aripiprazole has been reported to cause neuroleptic malignant syndrome.

Although aripiprazole appears to have little effect on prolactin secretion or the QT interval of the ECG, it is unclear if it has significant clinical advantages. Despite being approved for maintenance treatment there is little published information about the long-term safety and efficacy of aripiprazole. It needs to be compared with other atypical antipsychotics in long-term trials to establish its place in therapy.