Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study

Background: Previous studies that found an association between benzodi-azepines and suicidal behaviours were confounded by indication bias. Aims: To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines. Method: Patients >= 16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days -30 to -1 before the event) and two matched reference periods (days -120 to -91, and -90 to -61). Results: A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30-day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69-1.78) and 1.45 for suicide (1.34-1.57) in individuals with recent psychiatric history, and of 2.77 (2.69-2.86) and 1.80 (1.65-1.97) for individuals without. Conclusion: This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. Registration No. EUPAS48070 (http://www.ENCEPP.eu).