Promoting sleep health to mitigate the risk of nonmedical opioid use and opioid-related adverse events
Year: 2023
Type: article
Abstract: The opioid crisis is a major public health issue in the United States and abroad. Sleep disturbances including insomnia and sleep apnea are common among persons with opioid use disorder (OUD). Both acute and chronic opioid exposure are known to directly disrupt sleep[1, 2], yet the role of sleep in the onset, maintenance, and progression of OUD has not been fully delineated. A recent article by Chen et al. used a large cohort of participants from the UK biobank dataset to demonstrate that short and long sleep duration, daytime sleepiness, and symptoms of insomnia were associated with future opioid-related adverse events, including the onset of OUD and the incidence of opioid overdose[3]. Furthermore, the pattern of risk of opioid-related adverse events increased as the aggregate score for poor sleep increased, suggesting an exposure-response relationship between sleep and future opioid-related adverse events. This study highlights the importance of sleep health in combatting the opioid crisis. There is limited but converging evidence that sleep disturbance can be a risk factor for nonmedical opioid use and OUD. In general, sleep disturbances during early childhood, particularly short sleep duration, are associated with a number of medical conditions including chronic pain and mental health disorders[4]. A longitudinal study found that a mother’s ratings of their child’s sleep at age 3 to 5 were associated with the onset of alcohol and illicit drug use at age 12 to 14[5]. Likewise, another longitudinal study found that adolescents who reported sleep disturbances were more likely to engage in nonmedical opioid use in adulthood[6], and cross-sectional research using data collected from emergency departments reported an association between sleep disturbances and nonmedical prescription drug use in adolescents[7]. There is also some evidence that sleep disturbance in adulthood can lead to nonmedical opioid use, as data from the National Longitudinal Study of Adolescent to Adult Health suggest that symptoms of insomnia at ages 24 to 32 were associated with nonmedical prescription opioid use at ages 33 to 43[8]. Although these studies offer correlational evidence linking sleep disturbance to the onset of nonmedical opioid use, most research on sleep and opioids has been conducted in the context of OUD treatment or acute opioid dosing[1, 9]. Individuals in treatment for OUD often report persistent or worsening sleep quality across their lifetime[10]. In addition, individuals in OUD treatment might self-report better sleep quality than indicated by objective measures, as highlighted by Finan and colleagues in a study comparing electroencephalography (EEG) versus self-report in persons maintained on methadone or buprenorphine[11]. The EEG results from the Finan study suggest that persons on buprenorphine or methadone sleep an average of 4.16 hours per night, yet report 6.8 hours per night. Low sleep quality can lead to impulsive decision-making and low positive affect[12, 13], both of which can increase the risk of drug use during treatment. Furthermore, a recent study by Mukherjee et al. found that persistently low total sleep time was associated with return to opioid use following residential treatment[14]. There is a general understanding that the relationship between sleep and OUD treatment outcomes is bi-directional in nature[1, 15], and the strength of this relationship may be somewhat dependent on critical intermediaries such as emotional processes and stress[1]. However, the mechanisms that govern the relationship between sleep and opioid use before the onset of OUD are not well understood, and more research is needed to uncover the nuances of when and how poor sleep increases the risk of opioid-related adverse events such as nonmedical opioid use[15] and the onset of OUD. There are longitudinal modeling techniques[16] that can be used to leverage epidemiological data to examine whether the emergence of sleep disorders is associated with the onset of opioid-related adverse events, thus confirming and extending the recent findings of Chen and colleagues. For example, cross-lagged panel models[17] could be used to examine prospective reciprocal effects of sleep habits and opioid-related adverse events. Longitudinal mixture modeling techniques can be used to examine whether individuals can be classified into subgroups based on trajectories of sleep habits over time[18]. Techniques that incorporate survival analysis with mixture modeling (e.g. discrete-time survival mixture models, continuous-time survival mixture models)[19, 20] could determine whether trajectories of sleep problems over a specific time period predict time to emergence of opioid-related adverse events. Alternatively, the emergence of opioid-related adverse events could be modeled as a sequential process[21, 22], in order to examine whether specific trajectories of sleep habits over time are associated with specific trajectories of opioid-related problems and adverse events. Finally, there may be clinical utility in subtyping individuals into profiles based on multiple different sleep habits to identify (1) whether there are subgroups of individuals presenting with specific patterns of sleep symptoms, (2) predictors of transitioning between profiles over time, and (3) which profiles are most strongly associated with future opioid-related adverse events. In light of the ongoing opioid crisis, it is critical to promote health behaviors that might mitigate the risk of nonmedical opioid use, progression of nonmedical opioid use to OUD, and opioid overdose. Sleep disturbances and sleep disorders are common among persons with OUD[2, 10], and there is growing evidence that sleep might be a malleable target to prevent opioid-related adverse events. To date, there are few studies that provide mechanistic insight into the relationship between sleep and the onset of nonmedical opioid use and OUD. Preclinical and human laboratory studies can provide the most definitive evidence of mechanistic relationships between sleep and OUD, but advances in statistical modeling allow researchers to harness current longitudinal and/or epidemiological data sources to better understand how and when improving sleep health could prevent opioid-related adverse events. There is also an opportunity to collect drug/alcohol use outcomes in longitudinal intervention studies that aim to improve sleep at different points during development, such as adolescence or emerging adulthood. These studies would provide direct evidence of whether sleep disturbances might lead to opioid-related adverse events, and further support the importance of sleep health as one of many factors to prevent OUD. There are some practical measures related to sleep that could help to stymie the opioid crisis in the long term. While most primary care already includes some brief assessment of sleep health, clinicians might consider increasing the depth and frequency of sleep assessments, especially during adolescence or in the instance of opioid prescribing. Addressing sleep health during routine medical care, including regular conversations about sleep hygiene and initiation of cognitive behavioral therapy for insomnia (if warranted), could be part of a comprehensive public health initiative to mitigate the risk of opioid-related adverse events. Funding: This work was funding by the National Heart, Lung, and Blood Institute U01HL150835 (Huhn). Financial disclosure: ASH has consulted for Gilgamesh and receives research funding from Indivior through his university. JDE reports no conflicts. The work described here does not directly relate to these disclosures. Nonfinancial disclosure: None.
Source: SLEEP
Authors: Andrew S Huhn, Jennifer D Ellis
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Award: G4708079075
OpenAlex ID: W4378640384