A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder

Background: Abnormalities in circadian rhythms are prominent features of bipolar disorder. Disrupted circadian rhythms are associated with an increased risk of relapse in bipolar disorder. Normalizing the circadian rhythm pattern of bipolar patients may improve their sleep and lead to fewer mood exacerbations. This study evaluated adjunctive ramelteon for the treatment of insomnia and mood stability in euthymic bipolar patients. Methods: Participants with euthymic bipolar disorder and sleep disturbances were randomized to receive adjunctive ramelteon or placebo in addition to their regular psychiatric medications for up to 24 weeks or until they experienced a relapse (defined as a depressed or manic event). Results: 83 participants were randomized to receive ramelteon (n=42) or placebo (n=41). Forty participants relapsed (48.2%). Cox regression analyses indicated that participants who received ramelteon (odds ratio 0.48, p=.024) were less likely to relapse. Kaplan Meier curves also indicated longer median survival times in the ramelteon group (Mdn=188 days) versus the placebo group (Mdn=84 days) X2(1)=5.33, p=.02. There were no serious adverse events in this study. Limitations: This was a small study with only 83 participants. The one-week window of confirmed stability is shorter than time intervals used in other studies. Conclusions: The present study shows that ramelteon was effective in maintaining stability for individuals with bipolar disorder. Patients treated with ramelteon were approximately half as likely to relapse as patients treated with placebo throughout the 24-week treatment period. (C) 2012 Elsevier B.V. All rights reserved.