A double-blind, randomized, placebo-controlled plus open trial of adjunctive suvorexant for treatment-resistant insomnia in patients with bipolar disorder

Background: Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients. Methods: 36 BD outpatients (19 BDI, 69.4% female, 48.9 [± 15.2] years) were randomized for 1 week to double-blind suvorexant (10-20 mg/day) vs. placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for three months. Subjective and Objective Total Sleep Time (sTST and oTST) were assessed. Results: During the randomized-control phase (RCT), an overall increase in the oTST emerged, which was statistically significant for CK algorithm (p=0.035). The comparison between the suvorexant and the placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported. Discussion: Efficacy results are inconsistent. During the RCT phase only a small increase in the objective oTST emerged, while, during the open phase no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of drop-outs limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.