A Randomized, Double-Blind, Placebo-Controlled Study of 2 Dose Ranges of Paliperidone Extended-Release in the Treatment of Subjects With Schizoaffective Disorder

Objective: This study was designed to assess efficacy and safety of paliperidone extended-release (ER) in patients with schizoaffective disorder.

Method: A randomized, 6-week, double-blind, placebo-controlled study was conducted. Subjects with a Structured Clinical Interview for DSM-IV diagnosis of schizoaffective disorder, Positive and Negative Syndrome Scale (PANSS) total score ≥ 60, score ≥ 4 on ≥ 2 PANSS items (hostility, excitement, tension, uncooperativeness, poor impulse control), and Young Mania Rating Scale and/or Hamilton Depression Rating Scale, 21-item version scores ≥ 16 were eligible. Subjects received higher-dose (12 mg/d) or lower-dose (6 mg/d) paliperidone ER. Dose adjustments by 3-mg increments were allowed until day 15. The study was conducted from October 2006 through February 2008.

Results: A total of 316 subjects were randomly assigned to paliperidone ER lower dose (n = 109), higher dose (n = 100), or placebo (n = 107). Mean ± SD modal dose in lower- and higher-dose groups: 5.7 ± 0.9 and 11.6 ± 1.0 mg/d, respectively. Mean ± SE PANSS total score (primary outcome) improved significantly with higher-dose paliperidone ER versus placebo (-32.4 ± 2.1 versus -24.1 ± 2.1; P = .003). Change with lower-dose paliperidone ER (-27.7 ± 2.1) was not significantly different from placebo (P = .187). No new safety issues were identified; common adverse events were headache (placebo: 16.8%; paliperidone ER: lower dose, 13.9%, higher dose, 13.3%) and tremor (3.7%, 12.0%, 11.2%, respectively). Mean prolactin and weight changes were greater with active treatment than placebo.

Conclusions: Higher-dose paliperidone ER was effective and well tolerated in patients with acute schizoaffective disorder. These findings and those from a companion study constitute the first registration program for antipsychotic treatment in schizoaffective disorder.

Trial Registration: clinicaltrials.gov Identifier: NCT00397033

J Clin Psychiatry 2010;71(5):587-598

Submitted: July 28, 2009; accepted February 11, 2010.

Corresponding author: Carla M. Canuso, MD, Johnson & Johnson Pharmaceutical Research and Development, LLC, 1125 Trenton-Harbourton Rd-E12604, Titusville, NJ 08560 ([email protected]).