Drug overdose risk with benzodiazepine treatment in young adults: Comparative analysis in privately and publicly insured individuals

• Published in: Addiction (Abingdon, England) Vol. 119; no. 2; pp. 356 - 368
• Main Authors: Bushnell, Greta A., Rynn, Moira A., Gerhard, Tobias, Keyes, Katherine M., Hasin, Deborah S., Cerdá, Magdalena, Nyandege, Abner, Olfson, Mark
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-02-2024
• Subjects: Anxiety; anxiety disorder; benzodiazepine; Benzodiazepines; Benzodiazepines - therapeutic use; cohort; Cohort analysis; Cohort Studies; Comparative analysis; depression; Drug abuse; Drug overdose; Drug Overdose - drug therapy; Drug Overdose - epidemiology; Emergency medical care; Emergency services; Health insurance; Humans; Inpatient care; Medicaid; Mental depression; Overdose; pharmacoepidemiology; Poisoning; Prescription drugs; Retrospective Studies; Same day; selective serotonin reuptake inhibitor; Selective Serotonin Reuptake Inhibitors - therapeutic use; Serotonin reuptake inhibitors; Serotonin uptake inhibitors; United States - epidemiology; Young Adult; Young adults; United States; United States > US; overdose; selective serotonin reuptake inhibitor; poisoning; cohort; young adult; anxiety disorder; depression; benzodiazepine; pharmacoepidemiology
• ISSN: 0965-2140; 1360-0443; 1360-0443
• DOI: 10.1111/add.16359

Background and Aims
Benzodiazepines (BZDs) carry a risk for drug overdose and are prescribed alone or simultaneously with selective‐serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety and depression in young adults. We aimed to measure risks of drug overdose following BZD treatment initiation, and simultaneous BZD and SSRI initiation, compared with SSRI treatment alone in young adults with depression or anxiety.
Design, Setting, Participants
The cohort study used administrative databases covering privately (MarketScan, 1/1/2009–12/31/2018) and publicly (Medicaid, 1/1/2015–12/31/2016) insured young adults (18–29 years) in the United States. Those with depression or anxiety diagnoses newly initiating BZD or SSRI treatment (without BZD or SSRI prescriptions in prior year) were included. Simultaneous “BZD + SSRI” initiation was defined as starting BZD and SSRI treatment on the same day. The cohorts included 604 664 privately insured young adults (BZD = 22%, BZD + SSRI = 10%, SSRI = 68%) and 110 493 publicly insured young adults (BZD = 23%, BZD + SSRI = 5%, SSRI = 72%).
Measurements
Incident medically treated drug overdose events were identified from emergency department and inpatient encounters (ICD poisoning codes) within 6 months of treatment initiation. Crude and propensity‐score adjusted cumulative incidence and hazard ratios (HR) were estimated. Sub‐analyses evaluated drug overdose intent.
Findings
Adjusted HRs of drug overdose for BZD vs. SSRI treatment was 1.36 (95% confidence interval [CI]:1.23–1.51) in privately and 1.59 (95%CI:1.37–1.83) in publicly insured young adults. The adjusted HRs of drug overdose for BZD + SSRI treatment vs. SSRI treatment were 1.99 (95%CI:1.77–2.25) in privately and 1.98 (95%CI:1.47–2.68) in publicly insured young adults.
Conclusions
Among young adults in the United States, initiating benzodiazepine treatment for anxiety and depression, alone or simultaneously with selective‐serotonin reuptake inhibitors (SSRI), appears to have an increased risk of medically treated drug overdose compared with SSRI treatment alone. These associations were observed in publicly and privately insured individuals.