Importance: Benzodiazepines are prescribed for the treatment of adolescent sleep disorders; however, benzodiazepine overdoses occur, often in combination with opioids.

Question: Is benzodiazepine treatment for sleep, compared with alternative pharmacologic treatments (trazodone, hydroxyzine, and sedative-hypnotic Z-drugs), associated with increased risk of overdose among young people?

Findings: In this cohort study of 23 084 young people initiating benzodiazepine treatment and 66 706 initiating a comparator treatment, the risk of drug overdose in the 6 months after treatment start was elevated for young people starting benzodiazepine treatment compared with alternative treatments for sleep disorders. This risk was further heightened for young people with a recent prescription opioid fill.

Meaning: The findings of this study suggest that the elevated risk of drug overdose with benzodiazepine treatment compared with alternative pharmacologic treatments for sleep disorders is an important safety consideration when treating young people.