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.