
Risk of Overdose with Antipsychotic and Opioid Co-Prescription
Unintentional overdose with antipsychotics plus opioids. Researchers performed a population-based cohort study of the risk of overdose associated with co-prescription of antipsychotics and opioids.
RESEARCH UPDATE
Case Vignette
“Ms Rose” is a 63-year-old African-American female with schizoaffective disorder. Her psychotic disorder has been stable on ziprasidone, venlafaxine, and zolpidem as needed. She had surgical repair of a torn rotator cuff and was prescribed opioids (oxycodone) for postoperative pain. Two weeks later, her husband found her on the porch, unresponsive and not following commands. She was brought to the local
Opioid Prescriptions
More than half of
The Current Study
Accordingly, Szmulewicz and colleagues4 investigated this association in a population-based cohort. The authors studied patients aged 15 to 85 who filled an opioid prescription between 2004 and 2017, nested in the IBM MarketScan Commercial and Medicare supplemental claims database.
The investigators identified all individuals who filled a prescription for an antipsychotic (index date). Other inclusion criteria were continuous medical and prescription drug benefit coverage for 180 days before the index date, no evidence of
The primary outcome measure was emergency department visit or
After 1:1 propensity score matching, the cohort consisted of 62,604 patients newly exposed to a sedating antipsychotic plus opioids (“exposed”) and an equal number of patients newly exposed to a nonsedating antipsychotic plus opioids (“referent”). Mean patient age was 50, and 33% of the cohort was male. The most commonly prescribed opioids were hydrocodone, oxycodone, tramadol, and buprenorphine. The IR of overdose was 35 events per 1000 person-years in the exposed group, and 26 events per 1000 person-years in the referent group, corresponding to an adjust HR of 1.34 (95% CI 1.07-1.68). In sensitivity analyses, there was evidence for a dose-response relationship based on antipsychotic dosage. Findings were consistent across a number of other sensitivity and subgroup analyses.
Study Conclusions
The authors concluded that among patients receiving prescription
Strengths of the present study include the large sample size, consideration of many potential confounders, use of an active comparator, and multiple sensitivity analyses. Limitations include the observational study design, the potential for medication nonadherence during the follow-up period, and the use of a commercially insured population, and that fatal unintentional overdoses prior to hospitalization would have been missed.
The Bottom Line
Clinicians should consider the risk of unintentional overdose when prescribing
Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
References
1. Davis MA, Lin LA, Liu H, Sites BD.
2. FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. FDA. March 2019. Accessed October 26, 2021.
3. Buckley PF.
4. Szmulewicz AG, Bateman BT, Levin R, et al.
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