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.