Effects of suvorexant on diurnal cortisol and patient-reported stress during opioid withdrawal in a randomized trial

Decades of research efforts have described the negative impact that stress poses on successful treatment of Opioid Use Disorder (OUD). However, direct investigation of biological and self-reported stress, and the relationship between the two during opioid withdrawal is understudied. This study investigated whether a dual orexin-receptor antagonist alters the relationship between stress and opioid withdrawal among persons undergoing a buprenorphine taper. Persons diagnosed with OUD (N = 38) were enrolled in a residential, randomized controlled trial wherein they were stabilized on buprenorphine/naloxone before being randomized to receive 20 mg suvorexant, 40 mg suvorexant, or placebo. Participants then underwent a 4-day step-wise buprenorphine taper followed by a 4-day post-taper observation period. Patient-reported levels of stress, withdrawal, and craving, as well as salivary cortisol samples, were collected four times daily. The results demonstrated that total daily cortisol levels decreased during the buprenorphine taper across medication groups and were significantly lower in those administered suvorexant vs placebo. Those receiving suvorexant also rated their stress as significantly lower relative to placebo. A lagged statistical model assessing the relationship between daily reports of stress and diurnal cortisol slope found a reciprocal relationship between a flatter previous day cortisol slope with higher next day self-reported stress. Greater total daily cortisol was associated with greater opioid withdrawal severity, and greater patient-reported stress was associated with greater opioid withdrawal and craving throughout the study. These findings advance our understanding of the relationship among the orexin neurotransmitter system and stress during opioid withdrawal.