Covariates

In total, we assessed 115 covariates that we believed to be risk factors, or proxies for risk factors, for opioid overdose. We assessed demographic characteristics (age, sex, year, and region in the United States) on the date of oxycodone initiation (index date). Comorbidities, prior medications, and health care utilization measures were assessed during the baseline period, defined as 180 days before the date of oxycodone initiation. Comorbidities included pain conditions, psychiatric disorders, depression, neurological disorders, cancer, diabetes, liver disease, and kidney dysfunction as well as opioid abuse or dependence, intentional self-harm, and any drug use disorder or drug dependence. We assessed prior use of antidepressants other than SSRIs, benzodiazepines, muscle relaxants, antipsychotics, anticonvulsants, dementia drugs, triptans, and nonsteroidal anti-inflammatory drugs. Measures of health care utilization included number of physician visits and number of hospitalizations as well as hospitalization in the 30 days prior to oxycodone initiation and the number of unique drugs dispensed during the baseline period. We estimated the amount of prior nonoxycodone opioid exposure using morphine milligram equivalents (MMEs) as well as total oxycodone amount and nonoxycodone opioid amount dispensed on the index date (also in MMEs). Finally, we assessed exposure to other drugs that are known to affect CYP2D6 and CYP3A4 enzymes (eTable 2 in the Supplement) on the index date and estimated chronic disease burden with the combined comorbidity score (a combination of conditions in the Charlson and Elixhauser measures that better estimates patient mortality).³⁴