Sleep behavior traits and associations with opioid-related adverse events: a cohort study

Abstract

Study objectives: Opioid-related adverse events (OAEs), including opioid use disorders, overdose, and death, are serious public health concerns. OAEs are often associated with disrupted sleep, but the long-term relationship between poor sleep and subsequent OAE risk remains unknown. This study investigates whether sleep behavior traits are associated with incident OAEs in a large population cohort.

Methods: 444 039 participants (mean age ± SD 57 ± 8 years) from the UK Biobank reported their sleep behavior traits (sleep duration, daytime sleepiness, insomnia-like complaints, napping, and chronotype) between 2006 and 2010. The frequency/severity of these traits determined a poor sleep behavior impacts score (0-9). Incident OAEs were obtained from hospitalization records during 12-year median follow-up. Cox proportional hazards models examined the association between sleep and OAEs.

Results: Short and long sleep duration, frequent daytime sleepiness, insomnia symptoms, and napping, but not chronotype, were associated with increased OAE risk in fully adjusted models. Compared to the minimal poor sleep behavior impacts group (scores of 0-1), the moderate (4-5) and significant (6-9) groups had hazard ratios of 1.47 (95% confidence interval [1.27, 1.71]), p < 0.001, and 2.19 ([1.82, 2.64], p < 0.001), respectively. The latter risk magnitude is greater than the risk associated with preexisting psychiatric illness or sedative-hypnotic medication use. In participants with moderate/significant poor sleep impacts (vs. minimal), subgroup analysis revealed that age <65 years was associated with a higher OAE risk than in those ≥65 years.

Conclusions: Certain sleep behavior traits and overall poor sleep impacts are associated with an increased risk for opioid-related adverse events.

Keywords: Opioid-related adverse events; chronotype; insomnia; napping; opioid crisis; opioid use disorder; sleep health.

Graphical abstract

Figure 1.

Flowchart of participant selection. How participants with opioid-related adverse events were selected in the study. From the UK Biobank. OAE opioid-related adverse event.

Figure 2.

Poor sleep behavior impacts groups and their associated risk for incident OAEs. Groupings were based on poor sleep behavior impacts score (Minimal = 0–1, Mild = 2–3, Moderate = 4–5, and Significant ≥ 6). (A) Hazard ratios (±95% CI) for OAEs using Cox proportional hazards regression models adjusted for age, sex, education, and ethnicity; percentage of cohort by group in panel below (B) Unadjusted cumulative incidence plot showing percentage of cohort with a first diagnosis of OAE by group over time. Individuals at risk by sleep groups are reported in the lower table. OAE opioid-related adverse event. CI confidence interval.

Figure 3.

Subgroup analysis of OAE risk. Forest plot of hazard ratios with 95% confidence intervals for moderate/significant poor sleep behavior impacts (vs. minimal/none) and associated OAE risk based on subgroups of age, sex, BMI, smoking status, sleep disorders, preexisting pain, psychiatric illness, baseline opioid use, and baseline hsCRP level. For each subgroup, the size of the square is proportional to the number of participants. *Indicates statistical significance at the p < 0.0056 level after Bonferroni adjustment for multiplicity. OAE opioid-related adverse events. hsCRP High-sensitivity C-reactive protein. CI confidence interval.