Opioid Prescriptions Increase Risk of Substance-Related Morbidity

Patrick Quinn, PhD

Initial opioid prescription is associated with a 30-40% increase in risk of subsequent substance-related morbidity.

The findings suggested the increase is smaller than previously reported in other research. Further, the results supported the need for ongoing monitoring for mental health and substance use disorder among patients receiving opioid therapy.

Patrick Quinn, PhD, and colleagues examined the association between the start of opioid initiation among adolescents and young adults with following substance-related morbidity. The team analyzed data on patients aged 13-29 years old from a linkage of Swedish registries. Data included dispensed prescriptions, inpatient hospitalizations, outpatient specialist care, criminal convictions, causes of death, and family relationships. Opioid prescription initiation was defined as the date of the first dispensed opioid analgesic.

Patients were included if they were prescription opioid naïve by January 1, 2007. Those who turned 13 years old after January 1 were included at their birthday.

The team used 3 designs to compare opioid recipients with those who did not receive a prescription. First, they made demographically matched comparisons by matching individuals who received opioids 1:1 to randomly selected nonrecipients on the exact year and month of birth, sex, and county of residence at the start of eligibility.

Then the investigators compared new opioid recipients with new recipients of prescription nonsteroidal anti-inflammatory drugs. Finally, they compared sets of twins or larger sets of multiple birth individuals.

Quinn and the team examined indicators of substance-related morbidity. Using ICD-10 codes, they defined incidence as a code diagnosis of or death by nontobacco substance use disorder or overdose, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime.

The final cohort comprised more than 1.5 million patients and more than half (51.5%) were male. Among the patients, 12.6% initiated opioid therapy by December 13, 2013 (median age, 20.9 years old). A majority of treatment was initiated with codeine (56.3%) or tramadol (25.6%). Oxycodone was the most common strong opioid (8.3%).

Opioid recipients had twice the risk of incident substance-related morbidity (HR, 1.98; 95% CI, 1.91-2.07). The cumulative incidence of new substance-related morbidity within 5 years was 7.1% (9% CI, 6.9-7.2) for opioid recipients and 3.7% (95% CI, 3.6-3.9) for demographically matched nonrecipients.

The active comparator design cohort included 25.9% opioid recipients, of whom, 93.4% had no preexisting substance-related morbidity. 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 (HR, 1.29; 95% CI, 1.23-1.35).

Results were similar in the co-twin design among 3013 opioid recipients and 3107 nonrecipients (aHR, 1.43; 95% CI, 1.02-2.01). The findings were also maintained for those receiving opioids for dental indications and for those starting therapy with immediate-release weak opioids.

“This pattern suggests that it may be appropriate to view opioid initiation not as a singular influence on risk, but rather as one likely contributor among multiple broader pathways to adverse opioid-related outcomes,” the study authors wrote.

The study, “Association of Opioid Prescription Initiation During Adolescence and Young Adulthood With Subsequent Substance-Related Morbidity,” was published online in JAMA Pediatrics.