Can Blocking the Orexin System Enhance Sleep's Benefits to Therapeutic Exposure for PTSD?

Cognitive behavioral therapies (CBT) that include exposure to trauma memories are considered first line treatments for PTSD. However, approximately 1/3 of patients who complete CBT for PTSD do not achieve remission, and hyperarousal symptoms including sleep disturbances are less responsive to CBT than other PTSD symptoms. Despite these limitations, CBT outcomes are generally superior to outcomes of pharmacotherapy. It is, therefore, imperative to identify strategies to improve effectiveness of treatments for PTSD, particularly hyperarousal symptoms.

Disturbed sleep is common in PTSD. Studies of PTSD and anxiety and mood disorders have shown that impaired sleep before psychotherapy predicted less favorable responses. Sleep has been implicated in learning processes that are a key to adaptive processing of trauma memories such as extinction learning and generalization of extinction. Our recent PTSD study showed that preserved slow-wave sleep (SWS), less increase in rapid-eye-movement (REM) density, and reduced wake after sleep onset (WASO) during sleep following an evening session of written narrative exposure (WNE: writing about one's traumatic experience) was associated with greater PTSD symptom reduction. These findings suggest that increased nocturnal arousal compromises sleep's benefits to emotional processing of trauma memories. Identifying strategies to reduce nocturnal arousal and promote sleep characteristics associated with emotional adaptation could enhance PTSD treatment outcomes.

Orexins are neuropeptides implicated in regulating both sleep/wakefulness and emotional behaviors, including anxiety. Inhibiting the orexin system promoted slow-wave patterns and reduced wake in animal models. The first orexin receptor antagonist (suvorexant) was recently approved for treatment of insomnia. Suvorexant reduced WASO and latency to persistent sleep and increased SWS and REM sleep in humans with insomnia. In addition, administrations of orexin-A increased anxiety-like behaviors in rodents, and administrations of an orexin receptor-1 antagonist to mice facilitated extinction of conditioned fear, an animal model of recovery from PTSD and anxiety disorders.

Objective: To examine effects of blocking the orexin system with suvorexant after WNE on sleep, PTSD symptoms, and intersession habituation.

The investigators will utilize the WNE paradigm in which participants with PTSD write about their traumatic experiences in the evening and morning sessions with intervening sleep. Suvorexant or placebo will be administered after the evening WNE, and sleep will be recorded.