Evaluation of suvorexant for trauma-related insomnia.

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.

Blocking the orexin system following therapeutic exposure promoted between session habituation, but not PTSD symptom reduction.

There is a need to identify strategies to increase the effectiveness of treatments for posttraumatic stress disorder (PTSD). Sleep is often disturbed in PTSD and has been implicated in learning processes that underlie recovery from PTSD, including extinction of conditioned fear. Our prior study suggested that diminished arousal during sleep may enhance benefits of therapeutic exposure for PTSD. The orexin system regulates arousal, and blocking the system diminishes arousal and promotes sleep. We, therefore, examined whether a dual orexin receptor antagonist, suvorexant, administered following evening exposure sessions, would enhance their therapeutic effectiveness for PTSD. In this randomized double-blind placebo-controlled trial, adults with PTSD completed four written narrative exposure (WNE) sessions, two of which took place in the evening, and two the next morning. Participants received either suvorexant or placebo after each evening WNE. We found that suvorexant increased N3 sleep and decreased N2 sleep and rapid-eye-movement latency measured by polysomnography. Between session habituation indexed by subjective distress ratings was greater with suvorexant, but there was no group difference in the reduction of PTSD severity from baseline to 1-week follow-up. No safety concerns emerged. The present findings provide preliminary support for enhancement of an effect of therapeutic exposure for PTSD by suvorexant. Further studies with larger samples are needed to translate the present findings into clinical applications, including studies to develop optimal suvorexant administration and exposure session schedules to achieve persistent benefits to sleep and possibly greater treatment augmentation.