Evaluation of the efficacy and safety of paliperidone extended-release in the treatment of acute mania: A randomized, double-blind, dose-response study

BackgroundAtypical antipsychotics are effective in the treatment of bipolar I disorder. In this 3-week double-blind study, the efficacy and safety of paliperidone extended-release (ER) tablets were assessed in patients with acute mania.MethodsPatients experiencing a manic or mixed episode (Young Mania Rating Scale [YMRS] total score ≥ 20), were randomly assigned to 1 of 3 fixed doses of once-daily paliperidone ER (3, 6, or 12-mg), or placebo (1:1:1:1 ratio).ResultsIn total, 469 patients were randomly assigned to treatment with paliperidone ER 3 mg (n = 112), 6 mg (n = 120), or 12 mg (n = 115); or placebo (n = 122). Mean (SD) change in YMRS total score from baseline to the 3-week endpoint (primary variable) was statistically significantly different for the paliperidone ER 12 mg group (−13.5 [9.17], p = 0.025), but not the 6 mg (−11.4 [9.98], p = 0.57) or 3 mg (−9.1 [11.18], p = 0.79) groups compared with placebo (−10.1 [10.21]). Headache was the most common treatment-emergent adverse event (17% total paliperidone ER versus 12% placebo).LimitationsA statistically significant (p = 0.0032) treatment-by-country interaction occurred, which confounded interpretation of study results. Paliperidone ER and placebo did not differ statistically for the primary efficacy variable among patients from the United States sites (74% of the intent-to-treat analysis set).ConclusionsPaliperidone ER 12 mg/day was superior to placebo in the treatment of acute mania. Change from baseline in YMRS total score increased with the dose of paliperidone ER. Paliperidone ER was generally tolerated by patients with bipolar I disorder and no new safety signal was detected.