A randomized,placebo‐ and active‐controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder

Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, Berwaerts J. A randomized, placebo‐ and active‐controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder.
Bipolar Disord 2010: 12: 230–243. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: To evaluate the antimanic efficacy and safety of paliperidone extended‐release (ER) tablets in patients with bipolar I disorder. Methods: This study included a 3‐week, double‐blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9‐week, double‐blind, maintenance phase (paliperidone ER versus quetiapine). Patients n = 493; Young Mania Rating Scale (YMRS) score ≥ 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3–12 mg/day), quetiapine (400–800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy. Results: Paliperidone ER was superior to placebo at the 3‐week endpoint {primary outcome; least‐squares mean difference in change from baseline in YMRS scores 95% confidence interval (CI)]: ?5.5 (?7.57; ?3.35); p < 0.001} and noninferior to quetiapine at the 12‐week endpoint least‐squares mean difference (95% CI): 1.7 (?0.47; 3.96)]. The median mode dose during the 12‐week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (≥ 10%) treatment‐emergent adverse events during the 12‐week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase ≥ 7% from baseline to 12‐week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) ‘switched to depression’ at the12‐week endpoint. Conclusions: Paliperidone ER (3–12 mg/day) was efficacious and tolerable in the treatment of acute mania.