Antipsychotic – aripiprazole
As many as 45m people worldwide are believed to suffer from schizophrenia. Standard treatment is with antipsychotic drugs such as chlorpromazine or haloperidol, but these are frequently beset by side-effects, including weight gain, cognitive disorders and impaired motor function. Recently, atypical antipsychotics have been introduced and although they are much more expensive, they have fewer side-effects, so that patients are much more likely to comply with their dosing regimens.
A new antipsychotic medicine is being developed by Otsuka Pharmaceuticals and Bristol-Myers Squibb. Aripiprazole is a dual dopamine autoreceptor agonist and post-synaptic D2 receptor antagonist, a different mechanism from existing typical and atypical antipsychotics.1 It is also believed to act as a partial agonist at 5-HT1A receptors, and an antagonist at 5-HT2A receptors, which may contribute to its overall efficacy and its favourable side-effect profile.
In a 52-week study comparing it with haloperidol, it produced improvements in positive, negative and depressive symptoms of schizophrenia. In the trial, in 1,294 people diagnosed with acute relapse of schizophrenia, significantly fewer patients treated with the drug discontinued therapy for lack of efficiency or adverse events, notably extrapyramidal symptoms. A further 26-week study on 310 patients showed it was associated with significantly fewer relapses, and a two-fold increase in time to relapse compared with placebo. A third trial was carried out on 311 stable schizophrenia patients, who were switched from olanzapine, risperidone or haloperidol to aripiprazole. Overall, those switched to the new drug showed improvements in measures of safety and tolerability, and an improvement in their extrapyramidal symptoms.2
Further trials are being carried out on aripiprazole's potential as a treatment for bipolar disorder. In a Phase II multi-centre double-blind placebo-controlled randomised study in 262 patients diagnosed with acute mania, it was found to be significantly better than placebo in reducing acute manic symptoms. A total of 40% of patients given aripiprazole responded, against 19% of the placebo group.2 The drug has been submitted for FDA approval as a treatment for schizophrenia, under the trade name Abilify.