An assessment of iloperidone for the treatment of schizophrenia.

Iloperidone (Novartis' Zomariltrade mark) is an atypical antipsychotic agent for the treatment of schizophrenia. Current trends in the treatment of schizophrenia indicate that some atypical antipsychotics are being recommended as first-line therapy. Atypical antipsychotics, in addition to being dopamine (D) receptor antagonists, are all relatively potent serotonin (5-HT) receptor antagonists and are less likely than conventional dopamine antagonists to induce movement disorders. However, all of these agents differ in their receptor profiles and clinical profiles. Iloperidone, a benzisoxazole, is a mixed 5-HT(2A)/D(2)antagonist. Iloperidone was found to be more potent than its analogues when compared with haloperidol in antagonising climbing behaviour in mice. Iloperidone is extensively metabolised and the main circulating metabolite is reduced iloperidone. In patients treated with iloperidone, a low incidence of extrapyramidal symptoms and weight gain has been shown. Data from Phase II trials demonstrated efficacy in patients at doses of 8 mg/day and tolerability was good up to 32 mg/day. Phase III prospective, double-blind, randomised trials with iloperidone are in progress under the ZEUS (Zomariltrade mark Efficacy Utility and Safety) programme involving 3300 patients. Iloperidone, with a balance of activity at the dopaminergic and serotonergic receptors, has obvious advantages over clozapine and olanzapine, both of which have a similar receptor profile as they favour serotonergic over dopamine receptors. Iloperidone is likely to reach the market in 2001 and has favourable prospects in the atypical antipsychotic market for schizophrenia, which is expanding from US$ 1.5 billion in 2000 to US$ 3 billion in 2005.