Benzodiazepine may pose increased fracture hazard in kids

Children with anxiety disorders receiving treatment with benzodiazepine are at high risk of fractures in the upper and lower limb than those taking selective serotonin reuptake inhibitors (SSRIs), an effect that is not observed in young adults, a study has found.

“Paediatric fractures are most often caused by falls,” according to the researchers, adding that benzodiazepine treatment may have side effects that potentially contribute to unintentional falls, which can increase susceptibility to fractures.

The side effects include slowed reaction time, drowsiness, dizziness, and weakness. Therefore, “increased caution in the weeks after benzodiazepine initiation in children with anxiety disorders may be warranted,” they said. [https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or]

The current analysis included 120,715 children aged 6–17 years and 179,768 young adults aged 18–24 years who had been diagnosed with an anxiety disorder. There were 12,840 benzodiazepine initiators and 107,875 SSRI initiators in the child cohort, and 57,684 and 122,084, respectively, in the young adult cohort.

Benzodiazepine initiators in general were older, more likely to have panic disorder and recent emergency department visits, and less likely to have comorbid mental health diagnoses. Alprazolam and lorazepam were the most frequently used agents.

Three months after initiation, 8 percent of children and 11 percent of young adults on benzodiazepine remained on treatment, which was lower relative to more than half of SSRI initiators overall.

In children, crude incidence rates of upper and lower limb fractures during treatment were 33.1 per 1,000 person-years (PYs) among benzodiazepine initiators and 25.1 per 1,000 PYs among SSRI initiators. Adjusted incident rate ratio (IRR) 1.53 (95 percent confidence interval [CI], 0.94–2.50), while the incident rate difference (IRD) was 13.4 per 1,000 PYs, confirming a higher risk of fracture with benzodiazepines. [Pediatrics 2020;doi:10.1542/peds.2019-3478]

The risk was even more pronounced among children initiating long-acting benzodiazepines vs SSRIs (adjusted IRR, 2.30, 95 percent CI, 1.08–4.91).

On the other hand, incident fracture rates were lower in young adults, with small differences between treatments (adjusted IRR, 0.85, 95 percent CI, 0.57–1.27; adjusted IRD, −1.3 per 1,000 PYs). This finding may be attributed to several factors, the investigators said.

“Young adults are generally less active and experience fewer fall-related injuries than do children. Therefore, there may be less opportunity for benzodiazepine adverse effects to cause a fall that could result in fracture,” they pointed out. “Relatedly, young adults likely have more awareness of symptoms and side effects and autonomy over when medication is taken.” [https://www.cdc.gov/injury/wisqars/nonfatal.html; Med Sci Sports Exerc 2008;40:181-188]

Benzodiazepines are more commonly prescribed to young adults, and children who receive the treatment may generally have higher anxiety severity than young adults, a potential source of residual confounding, the investigators noted.

“Subthreshold or undiagnosed conduct disorder is another potential source of residual confounding more prevalent in children… In addition, our primary fracture outcome was uncommon in young adults and perhaps less clinically relevant than for children,” they continued.

Despite the presence of several limitations in the study, “the findings add to the limited understanding of benzodiazepine treatment safety in youth,” the investigators said. “Clinicians could advise caution in activities that increase the likelihood of a severe injury until it is clear how benzodiazepine treatment will affect the child.”