The Efficacy of Suvorexant in Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial
Condition: Sleep Disturbance; Craving; Cortisol; Hypersecretion
MeSH terms: Dyssomnias; Parasomnias; Substance-Related Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Insomnia is an extremely common and poorly treated problem in patients with substance use
      disorders (SUD)s undergoing rehabilitation treatment in a residential facility. The
      persistence of insomnia in substance use disorders (SUDs) may be associated with tonic levels
      of drug craving. Insomnia and craving can predispose to relapse in patients with SUDs.
      Insomnia and SUDs are independently associated with increased cortisol indicating
      physiological dysregulation of the stress response system including the
      hypothalamic-pituitary-adrenal (HPA) axis. Hence sleep disturbance, craving and increased
      cortisol leads to relapse in SUD subjects. Suvorexant, an orexin 1 / 2 receptor antagonist,
      approved by the FDA for the treatment of sleep disturbance in subjects with primary Insomnia.
      Previous animal studies report Orexin 1 receptor antagonist decreases craving and normal the
      HPA axis. However, the efficacy of suvorexant on sleep and craving in SUD subjects is not
      known. The primary aims of this study are-

        1. To determine if suvorexant will improve sleep quality (increased total sleep time, fewer
           awakenings), as measured through wrist actigraphy and the Insomnia Severity Index (ISI)
           in SUDs.

        2. To assess whether or not SUDs patients treated with suvorexant endorse scale items on a
           modified abuse liability assessment battery.

        3. To determine if daily reports of mood, stress, craving and sleep using Ecological
           Momentary Assessment (EMA data) change during the course of the study as patients with
           SUDs are treated with suvorexant.

        4. To determine if patients taking suvorexant will have a decrease in total daily salivary
           cortisol over the course of the study by collecting samples at five time points in a
           day, for two consecutive days at two different times in the study.
    

Detailed description: 
      Insomnia is an extremely common and poorly treated problem in patients with substance use
      disorders (SUD)s patients undergoing rehabilitation treatment in residential facility. The
      persistence of insomnia in substance use disorders (SUDs) may be associated with tonic levels
      of drug craving. Insomnia and craving can predispose to relapse in patients with SUDs.
      Insomnia and SUDs are independently associated with increased cortisol indicating
      physiological dysregulation of the stress response system including the
      hypothalamic-pituitary-adrenal (HPA) axis. Hence sleep disturbance, craving and increased
      cortisol leads to relapse in SUD subjects.

      Suvorexant is a novel orexin 1 and 2 receptor antagonist, FDA approved for the treatment of
      insomnia. Suvorexant may be differentially beneficial in patients with opioid dependence: 1)
      It is efficacious for treatment of insomnia in the general population, 2) Data from animal
      models of opioid dependence suggest that orexins may be involved in reward (opioid) seeking
      behavior and altered stress response while an orexin antagonist appears to decrease reward
      (opioid) seeking while normalizing HPA axis function. A medication that can improve sleep,
      decrease craving and normalize the HPA axis may theoretically be helpful in patients with
      SUDs. At this juncture, the literature supports the case for an open trial of Suvorexant for
      patients in residential care for SUDs, who complain of sleep disturbance. The patients will
      be at least 5 days post-withdrawal, in order to minimize the residual sleep complaints
      associated with that phase of treatment.

      In previous, well-designed, placebo-controlled clinical trials in patients with insomnia,
      suvorexant has been shown to be efficacious compared with placebo. However, substance
      dependent patients with insomnia were not included in these studies. Although, as a new sleep
      medication, suvorexant has been placed in Schedule IV by the FDA, the drug has not been
      studied in the context of its potential abuse liability when administered at bedtime at the
      therapeutic dose among patients in residential treatment for substance dependence disorders.
      A modified abuse liability protocol will therefore be incorporated in this pilot study.

      The hypothesis for this study are-

        1. Relative to a baseline, patients treated with suvorexant will experience an increase in
           total sleep time, fewer awakenings after sleep onset, and improved subjective sleep
           quality.

        2. Patients treated with suvorexant are not likely to endorse scale items associated with
           abuse liability 30 minutes after drug administration or the following morning.

        3. Relative to baseline, patients being treated with suvorexant are more likely to report
           improved moods, and decreased ambient craving.

        4. Relative to baseline, patients being treated with suvorexant are more likely to
           experience decreased total daily salivary cortisol over the course of 7 days of
           treatment with suvorexant.
    

Intervention name(s): Suvorexant 20 mg
Intervention type(s): Drug
Intervention description(s): Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia.
Other intervention name(s): Belsomra
Intervention MeSH terms: Suvorexant
Intervention model: Single Group Assignment
Intervention model description: We intend to evaluate the efficacy of suvorexant in a group of opioid dependent (n=14) and a group of alcohol dependent subjects (n=14) in a residential treatment facility. It is an open label trial on subjects with opioid or alcohol dependence who are 5to 10 days post withdrawal.
Masking: None (Open Label)
Primary purpose: Treatment