Mortality and Risks Associated With Benzodiazepine Discontinuation After Long-Term Use
The discontinuation of benzodiazepine in patients may cause more harm than good, according to research conducted by a team of researchers.1 Results from their comparative effectiveness study found an increased risk of harm among patients using prescribed benzodiazepine treatment long-term relative to continuing treatment.
Benzodiazepines are one of the most widely prescribed medication classes in the United States, but regular use has been shown to cause severe—and harmful—psychological and physical dependence.2 The study’s researchers investigated the effects of discontinuing the use of benzodiazepine in patients and whether that would reduce the risk of death and other harms.
Included in the study were patients receiving stable long-term treatment using benzodiazepines (n = 353,576). The comparative effectiveness study with a trial emulation approach was conducted by researchers using data from a US commercial insurance database. For the study, benzodiazepine discontinuation was defined as “no benzodiazepine prescription coverage for 31 consecutive days identified during a 6-month grace period after baseline.”
In total, the study included 213,011 patients with stable long-term benzodiazepine prescription use without opioid exposure and 140,665 patients with opioid exposure. Among the patients who were not exposed to opioids, the adjusted cumulative incidence of death after 1 year was 5.5% (95% CI, 5.4% to 5.8%) for discontinuers with an absolute risk difference of 2.1 percentage points (95% CI, 1.9 to 2.3 percentage points) higher than for nondiscontinuers. Further, the mortality risk was 1.6 (95% CI, 1.6 to 1.7) times that of the patients who did not discontinue use.
For those with opioid exposure, the adjusted cumulative incidence of death was 6.3% (95% CI, 6.0% to 6.6%) for those who discontinued use, an absolute risk difference of 2.4 95% CI, 2.2 to 2.7 percentage points) percentage points higher than for those who did not discontinue use. The mortality risk for those who discontinued use was 1.6 (95% CI, 1.5 to 1.7) times that of nondiscontinuers.
The study did have limitations. The data the authors used cannot accurately determine when a patient stopped consuming benzodiazepine and patients could also receive their medication from another source. Further, the researchers did not have information on which specific causes of death were elevated, which may have elucidated mechanisms.
“This study identifies small absolute increases in risk of harms among patients with stable long-term prescription benzodiazepine treatment who appear to discontinue relative to continuing treatment, including those with and without recent prescription opioid exposure. Policy broadly promoting benzodiazepine discontinuation may have unintended risks,” the researchers concluded.
References:
- Maust DT, Petzold K, Strominger J, Kim HM, Bohnert ASB. Benzodiazepine discontinuation and mortality among patients receiving long-term benzodiazepine therapy. JAMA Netw Open. Published online December 20, 2023. doi:10.1001/jamanetworkopen.2023.48557
- Edinoff AN, Nix CA, Hollier J, et al. Benzodiazepines: uses, dangers, and clinical considerations. Neurol in. 2021;13(4):594-607. doi:10.3390/neurolint13040059