Impact of major depression and antidepressant use on alcoholic and non‐alcoholic fatty liver disease: A population‐based study

Abstract Background and Aims The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non‐alcoholic fatty liver disease (NAFLD). Methods The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time‐varying covariates. Models were adjusted for age, sex, socio‐economic status and comorbidities. Results MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P < .01. Antidepressant usage was common in patients with ALD (47.4%) and NAFLD (40.8%). After adjusting for covariates, MDD (adjusted hazard ratio [AHR]: 0.80, 95% CI: 0.63‐1.02 for NAFLD; and AHR 1.01, 0.88‐1.15 for ALD) was not associated with improved decompensated cirrhosis‐free survival. The antidepressant mirtazapine was associated with worse decompensated cirrhosis‐free survival among NAFLD (AHR 2.16, 95% CI: 1.32‐3.52) and ALD (AHR 1.53, 1.09‐2.15) cohorts. Similarly, mirtazapine was associated with mortality in both cohorts. Conclusions MDD was not associated with worse outcomes for ALD or NAFLD. Mirtazapine was associated with an increased risk of decompensated cirrhosis or death, which was not observed with other antidepressants. Prospective studies are warranted to confirm these findings.