PALIPERIDONA

Conference Report From the 2009 American Psychiatric Association Annual Meeting: "A placebo-controlled Trial of Paliperidone palmitate for Acute Schizophrenia

Pandina GJ, Lindenmayer J, Lull J, et al. A randomized, double-blind, placebo-controlled, dose-response efficacy and safety study of paliperidone palmitate in adults with schizophrenia. 162nd Annual Meeting of the American Psychiatric Association; May 16-21, 2009; San Francisco, California. New research poster NR1-073.
Summary

Only 1 second-generation antipsychotic, risperidone, is available in a long-acting depot formulation. A related drug, paliperidone, is undergoing phase 3 clinical trials as a depot medication. In this multicenter, placebo-controlled, double-masked study funded by the manufacturer, 652 patients were randomly assigned in equal numbers to 4 conditions: 25 mg, 100 mg, or 150 mg of monthly paliperidone palmitate (PP) injections; or monthly placebo injections. In all 3 active treatment conditions, a loading dose of 150 mg PP was given 7 days before the first assigned dose injection. All subjects were at least 18 years old and had an acute exacerbation of schizophrenia with a minimum PANSS score of 60. The primary outcome measure was change in PANSS score.

The trial completion rate for 3 monthly doses was 52% to 55% in the active treatment groups compared with 43% in the placebo group. In an intent-to-treat analysis, the mean reduction in PANSS score was significantly greater by week 13 in PP-treated patients compared with the placebo group for all 3 doses (P < .034). Response rates correlated positively with PP dose; effect sizes were 0.26 for 25 mg, 0.47 for 100 mg, and 0.55 for 150 mg. The most common adverse effects were injection site pain and dizziness. Dose-related increases in weight and serum prolactin occurred in the PP-treated group; 13% of patients on 150 mg PP gained > 7% of baseline weight compared with 5% of patients on placebo.
Comment

Paliperidone, which is 9-hydroxyrisperidone, would likely be easy to use in a depot palmitate formulation. Unlike risperidone microspheres, which require refrigeration, PP is stable at room temperature. Risperidone microspheres must be injected with a large-bore needle every 2 weeks, and a 3-week delay in clinical effect complicates dosing. In this trial, PP was administered in the deltoid muscle with a loading dose followed by a dose in 1 week and then every 4 weeks. The medication, however, is not yet approved for clinical use, and further phase 3 trials are underway."