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

Abstract

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.