suvorexant and Substance-Withdrawal-Syndrome

There are currently 3 FDA approved treatments for alcohol use disorder (AUD) in the USA, opioid receptor antagonists such as naltrexone, disulfiram and acamprosate. To date, these have been largely inadequate at preventing relapse at a population level and this may be because they only target certain aspects of AUD. Recently, suvorexant, a dual orexin receptor antagonist, has been FDA approved for the treatment of insomnia. Importantly, sleep disruptions occur during both acute and prolonged alcohol exposure and sleep deprivation is a potent factor promoting relapse to alcohol use. In this mini review article, we explore the therapeutic potential of suvorexant for the treatment of AUD. In particular, we highlight that in addition to altering the motivational properties of alcohol, suvorexant may also address key physiological components associated with alcohol withdrawal and abstinence, such as sleep disruptions, which should in turn help reduce or prevent relapse.

Topics: Alcoholism; Animals; Azepines; Humans; Orexin Receptor Antagonists; Sleep Wake Disorders; Substance Withdrawal Syndrome; Triazoles

Topics: Analgesics, Opioid; Azepines; Buprenorphine; Craving; Double-Blind Method; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Sleep; Substance Withdrawal Syndrome; Treatment Outcome; Triazoles

Insomnia is a prominent complaint in patients with alcohol use disorders (AUD). However, despite the importance of sleep in the maintenance of sobriety, treatment options for sleep disturbance associated with a history of AUD are currently limited. Recent clinical trials have demonstrated that suvorexant, a dual Hct/OX receptor antagonist, normalizes sleep in patients with primary insomnia; yet, its potential for the treatment of sleep pathology associated with AUD has not been investigated in either preclinical or clinical studies.. This study employed a model whereby ethanol vapor exposure or control conditions were administered for 8 weeks to adult rats. Waking event-related oscillations (EROs) and EEG sleep were evaluated at baseline before exposure and again following 24 hr of withdrawal from the exposure. Subsequently, the ability of vehicle (VEH) and two doses (10, 30 mg/kg IP) of suvorexant to modify EROs, sleep, and the sleep EEG was investigated.. After 24 hr following EtOH withdrawal, the ethanol-treated group had increases in waking ERO θ and β activity, more fragmented sleep (shorter duration and increased frequency of slow wave (SW) and rapid eye movement [REM] sleep episodes), and increased θ and β power in REM and SW sleep. Suvorexant induced a dose-dependent decrease in the latency to REM and SW sleep onsets but also produced REM and SW sleep fragmentation and increased β energy in waking EROs when compared with VEH.. Taken together, these studies suggest that suvorexant has overall sleep-promoting effects, but it may exacerbate some aspects of sleep and EEG pathology.

Topics: Alcoholism; Animals; Azepines; Electroencephalography; Ethanol; Humans; Male; Orexin Receptor Antagonists; Rats; Rats, Wistar; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Sleep, REM; Sleep, Slow-Wave; Substance Withdrawal Syndrome; Time Factors; Triazoles

Topics: Adult; Azepines; Benzodiazepines; Female; Humans; Hypnotics and Sedatives; Muscle Hypotonia; Orexin Receptor Antagonists; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Triazoles