Suvorexant for Sleep Disturbance in Substance Use Recovery

Sleep disturbance is a common, yet often overlooked, part of substance use disorders (SUDs). During withdrawal, many people report difficulty falling asleep and staying asleep, and sleep disturbance may persist during long-term recovery. The severity of sleep disturbances have also shown to be a predictor of relapse and later substance use (Gyawali & James, 2023). With alcohol use disorder (AUD) specifically, insomnia is frequently reported, and untreated insomnia has been identified as a predictor of relapse even months after abstinence (Campbell et al., 2020).

Improving sleep during recovery shows promise in improving SUD treatment outcomes (Huhn et al., 2022). However, many traditional sleep medications are not recommended for people with SUD due to the elevated risk of misuse (Gyawali & James, 2023). Since sleep disturbances can continue even after the worst of withdrawal has passed, there is a strong need for medications to improve sleep without creating a new risk for misuse (Gyawali & James, 2023).

What Is Suvorexant?

Suvorexant is an FDA-approved medication to support sleep initiation and the treatment of insomnia (Campbell et al., 2020; Gyawali & James, 2023; Huhn et al., 2022). Unlike many traditional medications that promote sleep through brain sedation, suvorexant blocks the orexin receptors—receptors that regulate sleep-wake cycles, energy balance, and feeding behavior— and reduces the engagement of the brain’s active wakefulness. This essentially helps the body “turn down” alertness so sleep can occur more naturally (Huhn et al., 2022). 

The orexin receptors are also linked to brain systems involved in reward and motivation and have been associated with craving and drug-seeking behaviors (Campbell et al., 2020; Gyawali & James, 2023). 

Across SUDs, orexin has been associated with sleep disruption, drug and alcohol-seeking, and emotional symptoms that can occur during withdrawal (Campbell et al., 2020). Because orexin may be involved in both sleep problems and addiction-related symptoms, blocking orexin signaling may improve sleep while also supporting recovery-related outcomes such as withdrawal severity and craving (Campbell et al., 2020; Gyawali & James, 2023).

Because suvorexant may address insomnia without the misuse risks associated with many sleep medications, it has begun to attract interest as a potential treatment during withdrawal and early recovery, including alongside medications for opioid use disorder (OUD) and other evidence-based SUD care (Gyawali & James, 2023; Huhn et al., 2022).

What the Research Shows

Suvorexant and Treating Opioid Use Disorder 

In a randomized, double-blind, placebo-controlled clinical trial, 38 people with opioid use disorder (OUD) were first stabilized on buprenorphine/naloxone and then assigned to receive suvorexant (20 mg or 40 mg) or placebo. Buprenorphine/naloxone was reduced over four days, followed by four additional days of monitoring. Sleep was measured nightly using wearable sleep devices, and participants also completed standard assessments of withdrawal symptoms and medication “high” ratings to evaluate potential risk of misuse (Huhn et al., 2022).

Key Findings:

• Sleep improved. In analyses comparing suvorexant versus placebo, participants receiving suvorexant showed greater total sleep time during the four-day buprenorphine/naloxone dose-reduction period and during the four days after buprenorphine/naloxone ended (Huhn et al., 2022).

  
  

• Withdrawal symptoms decreased after buprenorphine/naloxone ended. In two-group comparisons, participants receiving suvorexant reported less self-reported withdrawal severity during the four-day monitoring period than those receiving placebo (Huhn et al., 2022).

  
  

• Craving signals improved. During the dose-reduction period, participants receiving suvorexant reported reduced opioid “wanting,” increased desire to avoid opioids, and greater perceived self-control over opioid use relative to placebo (Huhn et al., 2022).

  
  

• Benefits persisted after buprenorphine/naloxone ended. During the monitoring period after buprenorphine/naloxone ended, participants receiving suvorexant continued to report a higher desire to avoid opioids relative to placebo (Huhn et al., 2022).

  
  

• No clear misuse liability signal in this study. Ratings of “High” and “Liking” did not differ between groups, and participants assigned a low monetary “street value” to suvorexant. The study also reported no evidence of dose-dependent increases in misuse potential ratings and no serious adverse events in this trial (Huhn et al., 2022).

The study suggests suvorexant may be a promising adjunct during supervised opioid withdrawal because it improved sleep and showed favorable signals on withdrawal and craving outcomes without an misuse-potential signal under the conditions tested (Huhn et al., 2022).

References:

Campbell, E. J., Norman, A., Bonomo, Y., & Lawrence, A. J. (2020). Suvorexant to treat alcohol use disorder and comorbid insomnia: Plan for a phase II trial. Brain Research, 1728, 146597. https://doi.org/10.1016/j.brainres.2019.146597

Huhn, A. S., Finan, P. H., Gamaldo, C. E., Hammond, A. S., Umbricht, A., Bergeria, C. L., Strain, E. C., & Dunn, K. E. (2022). Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Science Translational Medicine, 14(650), eabn8238. https://doi.org/10.1126/scitranslmed.abn8238

Gyawali, U., & James, M. H. (2023). Sleep disturbance in substance use disorders: The orexin (hypocretin) system as an emerging pharmacological target. Neuropsychopharmacology, 48, 228–229. https://doi.org/10.1038/s41386-022-01404-3