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Original Investigation
August 10, 2020

Association of Opioid Prescription Initiation During Adolescence and Young Adulthood With Subsequent Substance-Related Morbidity

Author Affiliations
  • 1Department of Applied Health Science, School of Public Health, Indiana University, Bloomington
  • 2Department of Psychological and Brain Sciences, Indiana University, Bloomington
  • 3Center for Health and Medical Psychology, School of Law, Psychology and Social Work, Örebro University, Örebro, Sweden
  • 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 6School of Medical Sciences, Örebro University, Örebro, Sweden
JAMA Pediatr. Published online August 10, 2020. doi:10.1001/jamapediatrics.2020.2539
Key Points

Question  Is initiation of prescription opioid analgesics during adolescence and young adulthood associated with greater risk of substance-related morbidity?

Findings  In a nationwide Swedish cohort, 12.6% of opioid-prescription-naive adolescents and young adults were dispensed opioid prescriptions from 2007 to 2013. Opioid recipients had approximately 1% to 2% greater absolute risk of substance-related morbidity within 5 years compared with nonsteroidal anti-inflammatory drug recipients and nonrecipient co-twins (among twins and other multiple birth individuals).

Meaning  Findings from this study suggest that opioid initiation during adolescence and young adulthood may be associated with a small increased risk of substance-related morbidity.


Importance  Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity.

Objective  To examine the association of opioid initiation among adolescents and young adults with subsequent broadly defined substance-related morbidity.

Design, Setting, and Participants  This cohort study analyzed population-register data from January 1, 2007, to December 31, 2013, on Swedish individuals aged 13 to 29 years by January 1, 2013, who were naive to opioid prescription. To account for confounding, the analysis compared opioid prescription recipients with recipients of nonsteroidal anti-inflammatory drugs as an active comparator, compared opioid-recipient twins and other multiple birth individuals with their nonrecipient co-multiple birth offspring (co-twin control), examined dental prescription as a specific indication, and included individual, parental, and socioeconomic covariates. Data were analyzed from March 30, 2019, to January 22, 2020.

Exposures  Opioid prescription initiation, defined as first dispensed opioid analgesic prescription.

Main Outcomes and Measures  Substance-related morbidity, assessed as clinically diagnosed substance use disorder or overdose identified from inpatient or outpatient specialist records, substance use disorder or overdose cause of death, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime.

Results  Among the included cohort (n = 1 541 862; 793 933 male [51.5%]), 193 922 individuals initiated opioid therapy by December 31, 2013 (median age at initiation, 20.9 years [interquartile range, 18.2-23.6 years]). The active comparator design included 77 143 opioid recipients without preexisting substance-related morbidity and 229 461 nonsteroidal anti-inflammatory drug recipients. The adjusted cumulative incidence of substance-related morbidity within 5 years was 6.2% (95% CI, 5.9%-6.5%) for opioid recipients and 4.9% (95% CI, 4.8%-5.1%) for nonsteroidal anti-inflammatory drug recipients (hazard ratio, 1.29; 95% CI, 1.23-1.35). The co-twin control design produced comparable results (3013 opioid recipients and 3107 nonrecipients; adjusted hazard ratio, 1.43; 95% CI, 1.02-2.01), as did restriction to analgesics prescribed for dental indications and additional sensitivity analyses.

Conclusions and Relevance  Among adolescents and young adults analyzed in this study, initial opioid prescription receipt was associated with an approximately 30% to 40% relative increase in risk of subsequent substance-related morbidity in multiple designs that adjusted for confounding. These findings suggest that this increase may be smaller than previously estimated in some other studies.

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