Paliperidone: a review of clinical trial data and clinical implications

Paliperidone, 9-hydroxy-risperidone, is the major metabolite of the atypical antipsychotic risperidone and is available in an oral extended-release (ER) formulation. Paliperidone ER was approved for treating schizophrenia in 2006, and in 2009 it became the first atypical antipsychotic licensed for treating schizoaffective disorder. The short-term efficacy, safety and tolerability of paliperidone ER for patients with schizophrenia were demonstrated in three pivotal 6-week, randomized, double-blind, placebo-controlled studies. Data from the long-term trial showed that paliperidone ER is also effective in preventing relapse of schizophrenia. Two randomized, placebo-controlled, short-term studies have documented the efficacy and tolerability of paliperidone ER in the treatment of schizoaffective disorder, but no long-term or maintenance study has been conducted in patients with schizoaffective disorder. Two 3-week, randomized, double-blind, placebo-controlled studies showed that paliperidone ER is significantly superior to placebo for treating patients with bipolar disorder, but the results were driven by certain subpopulations. Limited evidence suggests that paliperidone ER can potentially be superior to quetiapine and risperidone. However, few direct head-to-head comparisons between paliperidone ER and other antipsychotics have been conducted to confirm these results. The distinctive pharmacological characteristics of paliperidone ER, including smooth fluctuations in plasma drug concentrations, predominantly renal excretion, low risk of causing hepatic impairment and low drug-drug interaction, might provide important clinical advantages compared with risperidone. However, certain side effects require clinical attention. The rate of extrapyramidal side effects was considerably higher than that of a placebo at doses ≥9 mg/day. The risks for orthostatic hypotension, prolongation of the corrected QT interval and hyperprolactinaemia are also concerns. This review summarizes the currently published data on paliperidone ER for treating patients with schizophrenia, schizoaffective disorder and bipolar disorder, and suggests its appropriate use in clinical practice.