Evaluation of suvorexant for trauma-related insomnia

Abstract

Study objectives: Effective pharmacological treatments for sleep disturbance related to trauma with and without co-occurring posttraumatic stress disorder (PTSD) are needed. There is debate regarding what effects on rapid eye movement sleep (REMS) would be beneficial. Suvorexant is the first dual orexin receptor antagonist (DORA) approved for the treatment of insomnia. In contrast to most psychotropic agents, DORAs can enhance REMS while reducing arousal. We evaluated 6 weeks of suvorexant treatment for trauma-related insomnia in a double-blind, placebo-controlled clinical trial with clinical and polysomnographic evaluation.

Methods: Participants with insomnia that followed a traumatic event were recruited from the community. Representation of current, past-only, and never having met criteria for PTSD was similar and most participants had experienced trauma-related nightmares. Participants were randomly assigned to receive suvorexant or placebo, initially at 10 mg and increased to 20 mg after 1 week, if tolerated. Polysomnography was obtained for screening, at baseline, and at 2 weeks of treatment.

Results: The thirty-seven evaluable participants had significant improvement of PTSD and insomnia symptoms, however, there were no significant interactions with treatment condition. Medication was well tolerated with only one dropout being related to side effects. Within the suvorexant group increased REM segment duration correlated with concurrent PTSD symptom reduction. Nightmares remitted in all of the participants who received suvorexant and all but one of those receiving placebo.

Conclusions: A robust placebo response undermined detecting a medication effect. Further evaluation of DORAs for trauma-related insomnia, as well as factors contributing to placebo-response, are warranted.

Trial registration: ClinicalTrials.gov NCT02704754.

Keywords: PTSD; insomnia; nightmares; suvorexant; trauma.