Four published primary reports of phase III studies were identified as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action and pharmacogenomic studies that identify potential genetic
biomarkers for efficacy and tolerability. Product labelling provided additional data.
DATA EXTRACTION: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labelling.
DATA SYNTHESIS:
Iloperidone is a second-generation
antipsychotic agent indicated for the acute treatment of
schizophrenia in adults.
Iloperidone has been evaluated in several double-blind placebo-controlled clinical trials. The oral formulation has demonstrated efficacy in reducing the symptoms of acute
schizophrenia at fixed daily doses ranging from 12 to 24 mg. Data reported for categorical definitions of response using the Positive and Negative Syndrome Scale were limited to one study and specifically to rates of achieving a > or = 20% decrease in the positive subscale from baseline; significantly more patients receiving
iloperidone 24 mg/day (72%) than placebo (52%) met this criterion, yielding a NNT of five.
Iloperidone should be titrated slowly to avoid
orthostatic hypotension, potentially delaying the achievement of a therapeutic dose level. There appears to be a dose relationship for adverse events such as
dizziness,
somnolence and dry mouth; for example NNH vs. placebo for
somnolence was 25 for
iloperidone 10-16 mg/day and 10 for 20-24 mg/day. There is a possibility of a therapeutic dose response as well.
Iloperidone is essentially free of extra-pyramidal side effects.
Iloperidone is associated with
weight gain comparable with
risperidone. Long-term double-blind maintenance studies have demonstrated
iloperidone's non-inferiority to
haloperidol for
relapse prevention. Product labelling includes a warning about the potential for QT interval prolongation. At present there are no efficacy studies available that are powered to directly compare
iloperidone with other second-generation
antipsychotics. The development of a depot formulation of
iloperidone as well as efforts to identify genetic
biomarkers for prediction of both efficacy and tolerability are in progress.
CONCLUSIONS: Aside from
paliperidone,
iloperidone is the first new second-generation
antipsychotic to be commercialised in the USA since 2002. From the limited registration data,
iloperidone appears to be relatively well tolerated once titrated to a therapeutic level and can be a useful option to consider. The development of a depot formulation and potential for genetic
biomarkers may make this agent compelling. Further comparisons with other available agents among patients with
schizophrenia in the 'real world' are needed.