Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal

Sleep. 2024 Apr 12;47(4):zsae025. doi: 10.1093/sleep/zsae025.

Abstract

Study objectives: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms.

Methods: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity.

Results: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (β = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: β = 2.579, d = 0.413, p = 0.009 | 40 mg β = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: β = 158.304, d = 0.397, p = 0.009 | 40 mg: β = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: β = 48.97, d = 0.410, p < 0.001 | 40 mg: β = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: β = 190.90, d = 0.308, p = 0.99 | 40 mg: β = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: β = 215.55, d = 0.034, p = 0.006 | 40 mg: β = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: β = -357.84, d = -0.659, p = 0.004 | 40 mg: β = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: β = 740.58, d = 0.964 p = <0.001 | 40 mg: β = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: β = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group.

Conclusions: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal.

Keywords: depression; power spectrum; sleep-EEG; suvorexant; withdrawal.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesics, Opioid* / adverse effects
  • Azepines*
  • Electroencephalography
  • Female
  • Humans
  • Inpatients
  • Male
  • Middle Aged
  • Sleep
  • Substance Withdrawal Syndrome*
  • Triazoles*
  • Young Adult

Substances

  • Analgesics, Opioid
  • Azepines
  • suvorexant
  • Triazoles