Lorazepam use during clinical trials of adults with bipolar mania episodes.

Background: Lorazepam has commonly been prescribed to reduce agitation during bipolar 1 mania trials. Its use has varied considerably by trial methodology and in clinical practice. Methods: The extent and amount of lorazepam treatment was recorded and analyzed from available brief, controlled trials of acute bipolar mania and in clinical reports in adults. Results: In 3-week, placebo-controlled clinical trials (n = 19), most manic subjects (79%) were treated with lorazepam to reduce agitation. This treatment was most prominent during the antimanic drug wash-out phase that preceded placebo-controlled trials. Doses of lorazepam administered during the first 7-10 days of the pre-trial and the early trial phases averaged 2.2 mg/day. These doses were one-third the lorazepam/clonazepam doses administered during placebo-controlled, non-washout trials. Far higher benzodiazepine doses for manic agitation were noted in emergency department reports. Intake enrollment was strikingly restricted only in placebo-controlled trials that used pretrial drug wash-out. Conclusions: Medication treatment conclusions from placebo-controlled, drug washout trials are not representative of clinical treatment for acute bipolar mania.