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

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.