Benzodiazepine use for anxiety disorders is associated with increased long-term risk of mood and substance use disorders: A large-scale retrospective cohort study.

Background: Benzodiazepines (BZDs) are widely prescribed for anxiety disorders. However, the long-term implications on mental health remain uncertain, especially the potential association between chronic BZD use and subsequent diagnosis of mood and substance use disorders (SUDs). Method: We conducted a 5-year retrospective cohort study by analyzing the TriNetX database, a real-time electronic medical record network. The study population was defined as patients aged 18-65 with anxiety disorders (ICD-10-CM: F40-F48). We employed propensity score matching to pair a BZD-exposed cohort (≥12 BZD prescriptions) with a BZD-unexposed control cohort. The outcomes were defined as depressive disorders, bipolar disorders, and SUDs. We employed Kaplan-Meier analyses to assess the survival probability over five years following diagnosis and BZD exposure; log-rank test to obtain the hazard ratio (HR) with 95 % confidence interval (CI). Results: We identified and matched 76,137 patients in the study and control cohorts. Compared to the control cohort, the BZD-exposed group exhibited significantly higher risks of being diagnosed with depressive disorders (HR, 2.64; 95 % CI, 2.59-2.68), bipolar disorders (HR, 4.39; 95 % CI, 4.15-4.64), overall substance use disorders (HR, 3.00; 95 % CI, 2.92-3.08), alcohol use disorder (HR, 3.38; 95 % CI, 3.20-3.57), stimulant use disorder (HR, 3.24; 95 % CI, 2.95, 3.55), cannabis use disorder (HR, 2.93; 95 % CI, 2.75-3.11), inhalant use disorder (HR, 4.14; 95 % CI, 3.38-5.06), and nicotine use disorder (HR, 2.72; 95 % CI, 2.63-2.81). Conclusion: Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs.