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-range21-63, 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 (ß = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg ß = 2.579, d = 0.413, p = 0.009 | 40 mg ß = 5.265, d = 0.847, p < 0.001) alpha power (20 mg ß = 158.304, d = 0.397, p = 0.009 | 40 mg ß = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg ß = 48.97, d = 0.410, p < 0.001 | 40 mg ß = 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 ß = 190.90, d = 0.308, p = 0.99 | 40 mg ß = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg ß = 215.55, d = 0.034, p = 0.006 | 40 mg ß = 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 ß = -357.84, d = -0.659, p = 0.004 | 40 mg ß = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg ß = 740.58, d = 0.964 p = <0.001 | 40 mg ß = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only ß = 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.