A randomized, placebo-controlled study of adjunctive ramelteon in ambulatory bipolar I disorder with manic symptoms and sleep disturbance.

This study evaluated the efficacy and tolerability of ramelteon in ambulatory bipolar I disorder with manic symptoms and insomnia. Twenty-one outpatients with bipolar I disorder by Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria with mild-to-moderate manic symptoms and sleep disturbance were randomized to receive either ramelteon (N=10) or placebo (N=11) in an 8-week, double-blind, fixed-dose (8 mg/day) study. Ramelteon and placebo had similar rates of reduction in ratings of symptoms of insomnia, mania, and global severity of illness. However, ramelteon was associated with improvement in a global rating of depressive symptoms. It was also well tolerated and associated with no serious adverse events. The small sample size may have limited the ability of the study to detect potentially clinically important drug-placebo differences. Further studies of ramelteon in subgroups of bipolar patients with sleep disturbance, including those with depression or euthymia, seem indicated.