The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia

Paliperidone extended-release (ER) is a newly commercialised antipsychotic formulated using the principal active metabolite of risperidone, 9-hydroxyrisperidone. It has been developed as an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and theoretically leading to a decreased incidence of adverse effects. Available data from preregistration, multicenter, short-term, double-blind, placebo-controlled studies indicate that paliperidone ER, at dosages of 3 – 15 mg/day, is relatively safe and well tolerated in adult patients with schizophrenia. As with risperidone, paliperidone may cause extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner. Preliminary long-term studies (up to 52 weeks) appear to confirm the findings from short-term trials indicating a low liability for paliperidone ER to cause metabolic effects (i.e., weight gain, hyperglycaemia and lipid dysregulation). Safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug–drug interactions.