Benzodiazepines increase drug overdose risk in youth

Benzodiazepines as treatment for sleep disorders have a greater risk of drug overdose in pediatric patients than alternative pharmacologic treatments, according to a recent study.

Inadequate sleep among adolescents was 66% in 2019—a 22% increase from rates in 1991— increasing risk of negative health consequences from insomnia. Treatments for insomnia are both nonpharmacologic and pharmacologic, but the recommended first-time treatment is cognitive behavioral therapy.

Many prescription pharmacologic treatments for treating insomnia are available, but these often have little or weak evidence on their safety and efficacy, especially for long-term treatment. One such treatment is benzodiazepines, a class of medications prescribed for treating sleep disorders in adults.

Benzodiazepines is often prescribed to pediatric patients, despite being recommended less frequently because of lacking evidence on their safety and efficacy in children. Currently, the recommended treatment period with benzodiazepines for all age groups is 4 weeks or less.

Nonmedical use, benzodiazepine use disorders, and overdose are all risks associated with overdose, and these risks increase if benzodiazepines are used with opioids and other central nerve depressants. Since the start of the prescription opioid epidemic, cases of morbidity and mortality from benzodiazepines have increased.

Overdose deaths from benzodiazepines were 1135 in 1999, 6872 in 2011, and 12,290 in 2020. However, data on the risks of drug overdose in youth prescribed benzodiazepines for insomnia is lacking.

To examine the association with benzodiazepines and drug overdose risk in young people, investigators conducted a study with a cohort from the 2009 to 2018 MarketScan US commercial claims database. This database includes data on dispensed prescription medications, insurance enrolment dates, and emergency department (ED) encounters.

Participants were young people with a sleep disorder diagnosis undergoing new use benzodiazepines, which was defined through a 1-year washout period where benzodiazepines and alternative treatments were not used. Patients using alternative pharmacologic treatment for sleep disorders were also included.

Cohort exclusions included epilepsy diagnosis, combination treatments, trazodone initiation at higher doses, clinical contraindications, and initiating treatment with 1 or more medication classes.

Alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, and triazolam were listed as prescription benzodiazepines.

Drug overdose was the primary outcome, and data was gathered from inpatient or ED records in the 6 months following treatment initiation. Categories of drug overdose included unintentional, intentional, and undetermined drug poisonings. Demographic characteristics and comorbid psychiatric diagnoses of patients were also gathered.

There were 23,084 participants in the study using benzodiazepines for treatment against sleep disorders, 90.3% of which were diagnosed for insomnia and 9.7% an unspecified sleep disorder. 

Characteristics were similar between new users of benzodiazepines and new users of alternative medications, but benzodiazepine initiators more often had recently used selective serotonin reuptake inhibitors. 

Benzodiazepine initiators were also more likely to have unspecified anxiety diagnoses and less likely to have been diagnosed with a prior substance use disorder, cannabis use disorder, or suicidal ideation. Treatment for pediatric patients was often 1 full prescription, with a median days’ supply of 20 days for benzodiazepineand 30 days for alternative medication.

Treatment was still being given to 22.9% of benzodiazepine users and 28.9% of the comparator group 3 months after treatment was initialized. At 6 months, this decreased to 9.7% of benzodiazepineusers and 12.3% of the comparator group.

There were 684 drug overdose events in the 6-month follow-up period, 190 of which were from benzodiazepine initiators. The incidence of drug overdose was 0.9% for benzodiazepine initiators and 0.8% for the comparator group at 6 months. After adjustment, this was 1% for benzodiazepine initiators and 0.8% for the comparator group.

Opioids had been prescribed to 13.8% of the cohort in the 3 months prior to treatment. Drug overdose among benzodiazepine initiators with a recent opioid prescription was 1.6%, and 0.8% for users of alternate medication with a recent opioid prescription.

These results showed that benzodiazepines increase risk of drug overdose among young people. Investigators recommended that health care providers discuss the risks with young people and review patient medications before prescribing benzodiazepines.

Reference

Bushnell GA, Gerhard T, Keyes K, Hasin D, Cerdá M, Olfson M. Association of benzodiazepine treatment for sleep disorders with drug overdose risk among young people. JAMA Netw Open. 2022;5(11):e2243215. doi:10.1001/jamanetworkopen.2022.43215