Sleep disturbance as a therapeutic target to improve opioid use disorder treatment.

Abstract

Sleep health is an important factor across several physical and mental health disorders, and a growing scientific consensus has identified sleep as a critical component of opioid use disorder (OUD), both in the active disease state and during OUD recovery. The goal of this narrative review is to collate the literature on sleep, opioid use, and OUD as a means of identifying therapeutic targets to improve OUD treatment outcomes. Sleep disturbance is common and often severe in persons with OUD, especially during opioid withdrawal, but also in persons on opioid maintenance therapies. There is ample evidence that sleep disturbances including reduced total sleep time, disrupted sleep continuity, and poor sleep quality often accompany negative OUD treatment outcomes. Sleep disturbances are bidirectionally associated with several other factors related to negative treatment outcomes, including chronic stress, stress reactivity, low positive affect, high negative affect, chronic pain, and drug craving. This constellation of outcome variables represents a more comprehensive appraisal of the quality of life and quality of recovery than is typically assessed in OUD clinical trials. To date, there are very few clinical trials or experimental studies aimed at improving sleep health in OUD patients, either as a means of improving stress, affect, and craving outcomes, or as a potential mechanistic target to reduce opioid withdrawal and drug use behaviors. As such, the direct impact of sleep improvement in OUD patients is largely unknown, yet mechanistic and clinical research suggests that therapeutic interventions that target sleep are a promising avenue to improve OUD treatment. Public Significance StatementIn light of the ongoing opioid crisis, there is a pressing need to improve treatment outcomes for opioid use disorder. Sleep disturbance is a common complaint among persons with opioid use disorder, and interventions that target sleep in this population could improve stress, affect, craving, and/or relapse outcomes.

Endogenous opioid signaling in the retina modulates sleep/wake activity in mice

“…Both acute and chronic opioid use produce sleep disturbances, which are associated with negative outcomes like depression and increased risk of relapse and dependence ( Tripathi et al, 2020 ; Huhn and Finan, 2021 ). Sleep disturbances have recently emerged as an important, yet understudied, therapeutic target for improving outcomes for individuals on long-term opioid therapy and medications for opioid use disorder (e.g.…”

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

“…In this study, we examined how three days of repeated morphine exposure and withdrawal can impact sleep behaviors acutely, as well as how it can alter the response to future sleep disruptions. Clinical data indicate that sleep disruptions commonly occur during and following withdrawal from many substances including alcohol, cannabis, and opioids [12,[15][16][17][18]. Additionally, there is increasing evidence that sleep disruptions may be a biological pressure for relapse, especially in alcohol and opiate withdrawal [17][18][19][20][21][22][23] .…”

“…Clinical data indicate that sleep disruptions commonly occur during and following withdrawal from many substances including alcohol, cannabis, and opioids [12,[15][16][17][18]. Additionally, there is increasing evidence that sleep disruptions may be a biological pressure for relapse, especially in alcohol and opiate withdrawal [17][18][19][20][21][22][23] . Some of the effects of opioids on sleep have been recapitulated in preclinical models with cats, rats, and neonatal mice [24][25][26].…”

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper

“…Sleep disturbances are a clinically meaningful and often severe feature of opioid withdrawal that may persist during long-term OUD recovery. Improving sleep during opioid withdrawal may have collateral benefits on OUD treatment outcomes ( 3 , 4 ); however, sedative-hypnotic medications (which are commonly used for sleep in medical practice) carry a substantial safety risk in persons with OUD ( 5 , 6 ).…”