From the Journals

Fracture risk higher for children with anxiety on benzodiazepines



Risk of fracture is higher in children and adolescents prescribed benzodiazepines for anxiety, compared with those on antidepressants, a new study found, which offers further argument for caution with this class of drugs in young patients.

Hispanic girl at medical appointment with a broken arm FatCamera/E+

In research published in Pediatrics, Greta A. Bushnell, PhD, of Columbia University in New York and colleagues, looked at private insurance claims data including prescription records from 120,715 children aged 6-17 years diagnosed with an anxiety disorder and from 179,768 young adults aged 18-24 years also diagnosed with anxiety.

The investigators compared fracture incidence within 3 months of treatment initiation between the group prescribed benzodiazepines for anxiety and the group prescribed SSRIs. Subjects prescribed both classes of drugs were excluded from the analysis.

Of patients aged 6-17 years, 11% were prescribed benzodiazepines, with the remainder receiving SSRIs. Children on benzodiazepines saw 33 fractures per 1,000 person-years, compared with 25 of those on SSRIs, with an adjusted incidence rate ratio of 1.53. These were fractures in the upper and lower limbs.

Similar differences in fracture risk were not seen among the young adults in the study, of whom 32% were prescribed benzodiazepines and among whom fracture rates were low overall, 9 per 1,000 person-years in both medication groups.

Several SSRIs have been approved by the Food and Drug Administration to treat anxiety disorders in children, but benzodiazepines are used off label in youth. The drugs most commonly prescribed in the study were alprazolam and lorazepam, and 82% of the group in this study aged 6-17 years did not fill their prescriptions beyond 1 month.

In adults, benzodiazepine treatment has been shown to cause drowsiness, dizziness, and weakness, which can result in injury, and it also is associated with increased risk of car accidents, falls, and fractures. The higher fracture rate among children on benzodiazepine treatment seen in this study is similar to rates reported in studies of older adults, Dr. Bushnell and colleagues noted.

The researchers could not explain why the young adults in the study did not see a higher risk of fractures on benzodiazepines, compared with that among those taking SSRIs. They hypothesized that young adults are less active than children, with fewer opportunities for falls, and there were few fractures among the 18- to 24-year-old cohort in general.

David C. Rettew, MD, from the University of Vermont in Burlington, commented in an interview that, while there are plenty of reasons to be cautious about using benzodiazepines in youth, “fracture risk isn’t usually very prominent among them, so it is a nice reminder to have this on the radar screen.” Most clinicians, he said, already are quite wary of using benzodiazepines in children, which is suggested by the small proportion of children treated with them in this study.

“It seems quite possible that children and adolescents prescribed benzodiazepines are quite different clinically than the group prescribed SSRIs, despite the strong measures the study authors took to control for other variables between the two groups,” Dr. Rettew added. “I’d have to wonder if those clinical differences may be behind some of the fracture rate differences” seen in the study.

Dr. Bushnell and her colleagues acknowledged this among the study’s several limitations. “It is unclear how much unmeasured differences in psychiatric condition severity exist between youth initiating a benzodiazepine versus SSRI and how anxiety severity impacts fracture risk.” The researchers also noted that they could not measure use of the drugs beyond whether and when prescriptions were filled.

Dr. Bushnell and colleagues’ study was funded by the National Institute of Mental Health and by grants from the Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, and the National Institutes of Health. One of its coauthors disclosed financial relationships with several pharmaceutical manufacturers. Dr. Rettew said he had no relevant financial disclosures

SOURCE: Bushnell GA et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2019-3478.

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