Paliperidone-ER: first atypical antipsychotic with oral extended release formulation

Paliperidone-extended release (ER) is an antipsychotic medication newly introduced in the USA and Europe in 2007. It is the first oral atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system (OROS), a well-established technology already in use for CNS drugs (e.g., methylphenidate and hydromorphone). Paliperidone was in the focus of investigations for years, as it is the major metabolite (9-hydroxyrisperidone) of the widely used atypical antipsychotic risperidone. Paliperidone-ER has demonstrated clinical efficacy, safety and good tolerability on a once-daily basis in three randomized, double-blind, placebo-controlled, 6-week-studies including patients with acute schizophrenia and one randomized, double-blind, placebo-controlled long-term study assessing recurrence of psychotic symptoms in patients with schizophrenia. Key features are predominant renal elimination, therefore low risk of interaction with other drugs, good efficacy against psychotic symptoms based on D2-receptor and 5HT2A-receptor antagonism and very low affinity for muscarinic receptors resulting in absence of anticholinergic side effects. The OROS-ER technology leads to considerably lower plasma peak levels compared with nonextended-release formulations, thus possibly reducing side effects.