Asenapine - an investigational drug being developed by Organon, the human healthcare business unit of Akzo Nobel, for bipolar I disorder and schizophrenia - was demonstrated to be more effective than placebo in treating acute manic and mixed episodes associated with bipolar I disorder, according to new phase III results, from a study presented at the American Psychiatric Association's 2007 Annual Meeting.
In the three-week study, patients treated with either asenapine or olanzapine experienced significant improvements in acute mania symptoms, versus patients given placebo. Both asenapine and olanzapine demonstrated superiority versus placebo by the second day of treatment and maintained this benefit throughout 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, M.D., Professor and Chair of the Department of Psychiatry and Behavioural 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 conducted at 55 centres including 29 sites in the United States enrolled 488 patients with a manic (69%) or a mixed episode (31%) of bipolar I disorder and a baseline Young Mania Rating Scale (YMRS) score =20 at entry. 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 randomly treated with 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 (neurological symptoms such as involuntary movement, rigidity, and tremors often associated with antipsychotic medications).
At day 2, both asenapine and olanzapine provided greater mean reductions in YMRS scores 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% in the asenapine group, 52.9% in the olanzapine group , and 36.2% in the placebo group. Most adverse events were mild to moderate. The most commonly reported AEs (>6%) with asenapine included 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% in the asenapine group, 7.9% in the olanzapine group, and 2.9% in the placebo group.
Asenapine was found to be effective and safe in the treatment of acute mania associated with bipolar I disorder in this study.
Bipolar disorder, commonly referred to as manic-depressive disorder, is a chronic, episodic illness characterized by mania (episodes of elevated moods, extreme irritability, and increased energy), depression (overwhelming feelings of sadness, suicidal thoughts), or a combination of both. Approximately 5.7 million people in the United States ages 18 and older (2.6 percent of the population) have bipolar disorder. The estimated annual costs in the United States related to bipolar disorder exceed $8.5 billion.