Antipsychotic — iloperidone
Schizophrenia is estimated to affect around 45m people around the world. One of the staple treatments is with antipsychotic drugs such as haloperidol. Because of the side effects, such as impaired motor function, weight gain and cognitive disorders, there is a need for new drugs that are effective in a wider spread of schizophrenic patients and are better tolerated.
The new drugs being developed are classed as atypical antipsychotics. They are relatively potent serotonin receptor antagonists as well as having antidopamine activity, and are less likely to cause disorders than earlier antipsychotic agents.1
A new atypical antipsychotic, iloperidone, was discovered by Titan Pharmaceuticals, and is being developed in conjunction with Novartis.2 The compound is a mixed 5-HT2A/D2 antagonist,3 and was shown to be more potent than haloperidol in animal studies.4 Phase II trials showed it was tolerated at up to 32mg/day.
A double-blind, randomised Phase III trial in 3,700 patients is being carried out at over 300 centres around the world. Most of its activity is at the dopamine and serotonin receptors, which is believed to give it an advantage over the atypical antipsychotics clozapine and olanzapine which favour serotonin receptors over dopamine ones. A recently completed trial showed a statistically significant improvement in symptoms at doses of 20–24mg/day, and some improvement over placebo at 12–16mg/day.
Long-term trial data from three double-blind safety studies showed only a small weight gain and few extrapyramidal symptoms in treated patients, in addition to low sedation and low incidence of cardiovascular problems.
Additional studies on the drug are now under way. These will look further at once daily dosing, and are hoped to show a favourable safety profile when changing over from other antipsychotics to iloperidone and support the competitive profile of the compound. Further studies for additional indications such as acute mania are planned.