Benzodiazepine Use for Sleep Disorders May Increase Overdose Risk in Youth

Adolescents and young adults taking benzodiazepines demonstrated increased risk for drug overdoses, especially when being treated with concurrent opioids, compared with those taking alternative sleep disorder medications without opioids, according to study findings published in JAMA Network Open.

Researchers in the United States (US) conducted a cohort study, collecting data from the US commercial claims database, MarketScan, on 23,084 patients (62.6% female; mean age, 23 years) who initiated treatment with benzodiazepines compared with 66,706 patients (57.6% female; mean age, 22 years) who initiated treatment with an alternative medication for sleep disorders.

The researchers analyzed the association between benzodiazepine use and increased risk for drug overdose within the first 6 months after benzodiazepine treatment initiation in the adolescent and young adult population compared with other sleep disorder treatments. Comparator medications included trazodone, hydroxyzine, and Z-drugs.

After 6 months, 9.7% of the 23,084 adolescents and young adults were still receiving treatment with benzodiazepines, while 12.3% of the 66,706 patients in the comparator group were still receiving treatment.

They assessed the number of individuals treated in the hospital or emergency department setting for drug overdoses in both groups. Drug overdose occurred in 0.9% of patients in the benzodiazepine group compared with 0.8% in the comparator group.

Initiating treatment with benzodiazepines carried an increased risk for drug overdose compared with alternative treatments for sleep disorders (intention-to-treat analysis hazard ratio [HR], 1.25; 95% CI, 1.03-1.5; as-treated analyses HR, 1.44; 95% CI, 1.14-1.80).

The researchers observed that the association between benzodiazepine use and drug overdoses became stronger among youth who also filled opioid prescriptions around the same time (as-treated analysis HR, 2.01; 95% CI, 1.24-3.25) compared with youth who did not take concurrent opioids (HR, 1.31; 95% CI, 1.00-1.70).

Compared with alternative pharmacologic treatments for sleep disorders, during the 6-month period of starting benzodiazepines, young people were at a higher risk for drug overdose, the researchers noted. “Drug overdose is an important safety consideration when treating young people with benzodiazepines,” they said.

Study limitations included residual confounding by unassessed alcohol and drug use, potentially missed overdoses (including those leading to death) that did not result in hospital or emergency department medical encounters, lack of inclusion of the washout period following treatments for sleep disorders, lack of assessment of over-the-counter medications and sleep aids used for insomnia, and lack of differentiation of specific sleep disorders involved.  

Disclosures: Some study authors reported conflicts of interest. Please see the original reference for a full list of authors’ disclosures.