Association of benzodiazepines, Z-drugs, pregabalin, and melatonin with traffic accidents: A nationwide cohort and case-crossover study in Danish adults.

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 ( = 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% ( = 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) = 1.76, 95% confidence interval (CI): 1.67-1.86 and HR = 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.