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Background: A substantial proportion of patients with bipolar disorder are characterized by a rapidly cycling course and are particularly resistant to conventional treatment., Methods: This secondary analysis, defined a priori, was conducted on a larger data set from patients with bipolar I disorder to determine the efficacy of a 3-week treatment with the atypical antipsychotic olanzapine (5-20 mg/day, n=19) versus placebo (n=26) in patients with >or=4 episodes in the preceding year., Results: Significantly fewer placebo patients completed treatment (34.6 vs. 73.7%, P=0.016), and more than half discontinued due to lack of efficacy (53.8 vs. 21.1%, P=0.035). Olanzapine reduced Young Mania Rating Scale (YMRS) total scores significantly more than placebo (-13.9 vs. -4.1, P=0.011). Clinical responses, defined as >or=50% improvement in YMRS, were achieved in 58% of olanzapine patients, compared with 28% of placebo patients (P=0.066). Extrapyramidal symptoms were not significantly changed in either group. Somnolence was the most common adverse event in both groups (olanzapine: 52.6%, placebo: 23.1%; P=0.060). No event occurred significantly more frequently with olanzapine than with placebo. No patients discontinued due to an adverse event., Limitations: The duration of this study was limited to 3 weeks, precluding conclusions about long-term efficacy of olanzapine. Moreover, a sizeable placebo effect was obtained, possibly masking optimal therapeutic effect. Despite these limitations, treatment differences in efficacy were highly significant., Conclusions: These results indicate that olanzapine was effective in reducing symptoms of mania and well tolerated in patients with bipolar I disorder with a rapid-cycling course.

Introduction: An important consideration in treating acute mania is the promptness with which a chosen therapy can bring symptom amelioration. This article reviews the available published data from controlled, blinded studies regarding the latency of responses to antipsychotics in patients with acute mania. Methods: Articles for this review were obtained from a search of the Medline database (1966–1999), using the following keywords and phrases: antipsychotic, atypical, bipolar disorder, mania, neuroleptic, typical. The bibliographic sections of articles gleaned from this search were used to direct further inquiries. Results: Although information regarding the onset of action of antipsychotics is limited, we discovered data for four typical and three atypical antipsychotics. Drugs with the fastest onsets include haloperidol, risperidone, and olanzapine, with onsets appearing in 2–6 days. Chlorpromazine and thiothixene were at the slowest end of the continuum, with onsets of 2 weeks or longer. Data regarding pimozide are mixed, with some studies showing an onset equivalent to that of the ‘fast’ compounds and others showing one similar to that of the ‘slow’ compounds. Conclusions: Choice of therapy should consider not only efficacy and safety, but also onset speed. Atypical antipsychotics appear to offer safer, faster, and more effective therapies. [ABSTRACT FROM AUTHOR]