BACKGROUND: Benzodiazepines, Z-drugs, pregabalin, and melatonin (BZPMs) have been associated with a higher risk of traffic accidents, but the evidence is inconsistent, and lacking for newer drugs.

AIM: To examine the association of BZPMs with risk of traffic accidents.

METHODS: All Danish adults (n = 3,823,588) were followed for redeemed prescriptions of BZPM and for incident traffic accidents registered in Danish registers from 2002 through 2018. Associations were examined in cohort and case-crossover designs using Cox proportional hazard and conditional logistic regression with adjustment for co-variables.

RESULTS: A total of 19.3% (n = 738,019) of all participants initiated treatment with BZPMs. During the mean follow-up of 10.3 years, 595,173(15.5%) of participants were involved in a traffic accident. In the cohort analysis, all BZPMs besides pregabalin were associated with a higher risk of traffic accidents in adults below 70 years, with chlordiazepoxide showing the strongest association (hazard ratio (HR)age 18-49 = 1.76, 95% confidence interval (CI): 1.67-1.86 and HRage 50-69 = 1.84, 95% CI: 1.70-2.00). In the older age groups, the specific BZPM medications were associated with lower or no risk of traffic accidents. However, in case-time-crossover analysis with inherited control for confounders, no BZPM medication was positively associated with traffic accidents, except for chlordiazepoxide, which had a higher odds ratio in middle-aged group (1.62, 95% CI: 1.15-2.29).

CONCLUSIONS: This study does not fully support that BZPM use is a risk factor for traffic accidents. However, a positive association was found for chlordiazepoxide, which is approved for treatment of acute alcohol withdrawal.