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Benzodiazepines for Sleep Disorders Linked to Increased Risk for Drug Overdose among Youth


New findings suggest that the elevated risk of overdose with benzodiazepine use for sleep disorders is a critical safety consideration when treating young people.



Benzodiazepines, compared with alternative pharmacologic treatments for common sleep disorders, were associated with an increased risk of drug overdose among young people in a cohort study of more than 20 000 participants. The increased risk was observed during the first 6 months after treatment initiation and was highest for patients who began benzodiazepines with a concurrent opioid prescription.

“Adolescence and young adulthood are critical periods to consider drug overdose risk after prescription benzodiazepine treatment,” wrote a team of researchers from Rutgers University in JAMA Network Open. During adolescence, initial exposure to alcohol and other drugs often occurs along with a rise in nonmedical prescription drug use and prescription benzodiazepine misuse, according to investigators.

"Given the availability of alternative pharmacologic treatments for sleep disorders, it is important to examine whether increased overdose risk is associated with benzodiazepine treatment compared with commonly prescribed alternative medications,” wrote the team, led by Greta Bushnell, PhD, a faculty member at the Center for Pharmacoepidemiology and Treatment Sciences at the Rutgers Institute of Health, Health Care Policy and Aging Research.

Investigators sought to evaluate whether benzodiazepine treatment for sleep disorders, compared with alternative pharmacologic treatments (eg, trazodone, hydroxyzine, and sedative-hypnotic Z-drugs), was associated with increased risk of overdose.

The study included privately insured individuals aged 10 to 29 years identified from the MarketScan commercial claims database from January 2009 to December 2018. Young people with a sleep disorder diagnosis initiating benzodiazepine (n = 23 084; mean age, 23 years) or comparator pharmacologic treatments (n = 66 706; mean age, 22 years) were enrolled in the study.

Bushnell and colleagues found that 6 months after the start of treatment, 9.7% (95% CI, 9.3%-10.1%) of the benzodiazepine group and 12.3% (95% CI, 12.1%-12.6%) of the comparator arm were still receiving treatment. The crude incidence of drug overdose at 6 months was 0.9% for benzodiazepine users and 0.8% for comparator treatment initiators, according to the study results. The research team obtained information on incident diagnosed drug overdoses from inpatient and emergency department records.

In adjusted analyses, an increased risk of drug overdose was associated with benzodiazepines vs comparator treatments (intention-to-treat analysis: HR, 1.25 [95% CI, 1.03-1.51] as-treated analysis: HR, 1.44 [95% CI, 1.14-1.80]). Moreover, the association was stronger among young individuals with a recent prescription opioid fill compared with those without a recent prescription opioid fill (as-treated analysis: adjusted HR, 2.01 [95% CI, 1.24-3.25] vs adjusted HR, 1.31 [95% CI, 1.00-1.70]).

“With the lack of large, head-to-head trials of benzodiazepine and alternative sleep medications among young people, continued observational research on the comparative safety of pharmacologic treatments for sleep disorders is necessary to guide treatment decisions," concluded Bushnell et al. “By quantifying the 6-month risk of drug overdose after benzodiazepine treatment initiation for sleep disorders and providing comparative estimates on drug overdose among initiators of other pharmacologic interventions, we hope to inform prescribing decisions and encourage close monitoring for this young patient population.”

Reference: Bushnell G, Gerhard T, Keyes K, et al. Association of benzodiazepine treatment for sleep disorders with drug overdose risk among young people. JAMA Netw Open. 2022;5:e2243215. doi:10.1001/jamanetworkopen.2022.43215.

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