Higher Opioid Medication Dose and Discontinuation Are Weakly Associated With Substance-related Morbidity

Efforts to decrease prescription opioid-related harms may have unintended consequences. This US employer-based insurance claims study of adolescents and adults ≤65 who initiated long-term opioid therapy in 2010–2018 (N=194,838) examined the associations of prescribed opioid dose and opioid discontinuation with substance-related morbidity events. Adverse events included emergency visits, inpatient hospitalizations, and ambulance transportation with diagnoses of non-tobacco substance use disorder or overdose.

• Patients were followed for a median of 965 days. There were 17,582 acute substance-related morbidity events (2.41 events per 1000 person-months or 1 in 384 person-months).
• In adjusted analyses, risk of substance-related morbidity was greater when opioid medication doses were higher (odds ratio [OR], 1.29 for doses >60 to 120 morphine milligram equivalents [MME] per day; OR, 1.48 for doses >120 MME per day), compared with the initial period of prescribing.
• Risk of substance-related morbidity was greater during days 1–30 after medication discontinuation versus during initial treatment (OR, 1.19), but not greater than during the 30 days before discontinuation.

Comments: This study generally confirms an association between higher-dose opioid medication prescribing and adverse events, although adverse event rates were low compared with prior studies, likely reflecting the current study’s lower-risk insured population and improved control for confounding. These data support caution in ascribing adverse events to either opioid dosing or opioid discontinuation, as both may at least partially reflect pre-existing patient comorbidity.

Joseph Merrill, MD, MPH

Reference: Quinn PD, Chang Z, Bair MJ, et al. Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy. Pain. 2022;163(4):e588-e595.