The investigational agent asenapine is more effective than placebo in treating acute manic and mixed episodes associated with bipolar I disorder, according to phase III study results presented at the annual meeting of the American Psychiatric Association.

In the 3-week study, patients treated randomized to either asenapine or olanzapine showed significant improvement in symptoms of acute mania compared with those randomized to placebo. Both active agents showed superiority versus placebo by the second day of treatment and maintained significant benefit throughout the course of the trial.

"The consequences of untreated mania in patients with bipolar disorder can be devastating to patients and their families. We need more effective and more tolerable treatments for these patients," said Robert Hirschfeld, MD, Professor and Chair of the Department of Psychiatry and Behavioral Sciences at The University of Texas Medical Branch, Galveston. "The results of this trial suggest that asenapine is an attractive option for the acute treatment of mania because of its rapid onset of action and modest side effect profile.”

The Phase III, double-blind, international trial enrolled 488 patients with a manic (69 percent) or mixed episode (31 percent) of bipolar I disorder and a baseline Young Mania Rating Scale (YMRS) score greater than or equal to 20. The YMRS is an 11-item scale used to evaluate manic symptoms; a score of at least 20 represents moderate-to-severe mania.

Patients were randomized to asenapine (5-10 mg twice daily; average daily dose, 18.2 mg), olanzapine (5-20 mg once daily; average daily dose, 15.8 mg), or placebo for three weeks. Dosing was flexible. The primary efficacy endpoint was a reduction in YMRS total score at day 21. Safety measures included adverse events, weight gain and scores on measures of extrapyramidal symptoms.

On day 2, both asenapine and olanzapine provided greater mean score reductions versus placebo (-3.0 and -3.4, respectively, vs. -1.5; p<0.008 for asenapine, p<0.001 for olanzapine). At the end of the trial (day 21), both active treatments continued to produce significant mean improvements in mania symptoms versus placebo (-10.8 and -12.6, respectively, vs. -5.5; both p<0.0001).

The overall incidence of treatment-related adverse events was 60.8 percent for asenapine, 52.9 percent for olanzapine, and 36.2 percent for placebo. Most adverse events were mild to moderate, with the most common events (>6 percent) for asenapine including sedation, dizziness, headache, somnolence, and fatigue.

Olanzapine was most commonly associated with sedation, dry mouth, dizziness, headache, somnolence, and weight gain.

The incidence of extrapyramidal symptoms reported as an adverse event was 7.2 percent for asenapine, 7.9 percent for olanzapine, and 2.9 percent for placebo.