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.

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

“…Bile acids participate in a range of important host functions such as monoamine neurotransmitters, short-chain fatty acids, and indoles [ 75 ]. Non-alcoholic fatty liver disease has complex pathogenic mechanisms for MDD [ 76 ]. In addition, the liver is involved in the metabolism of many stress hormones, and neurotransmitters, for example, Cytochrome P450 (CYP), which is primarily expressed in the liver, are some of the main metabolizers of glucocorticoids and monoamines in the peripheral system [ 77 ].…”

Depression in nonalcoholic fatty liver disease and all‐cause/cause‐specific mortality

“…A recent study using the electronic medical records database from the United Kingdom showed higher survival rates among patients with the diagnosis of NAFLD and major depressive disorder compared to those without major depressive disorder 18 . However, the findings in the referenced study did present a caveat that major depressive disorder and antidepressants in patients with NAFLD were not independent predictors of improved decompensated cirrhosis‐free survival over a median 3‐year follow‐up 18 . These findings in this study can be explained by linkage‐to‐care and closer follow‐up with healthcare providers as a consequence of comorbid major depressive disorder.…”

“…These findings in this study can be explained by linkage‐to‐care and closer follow‐up with healthcare providers as a consequence of comorbid major depressive disorder. In addition, this study utilized Read code (such as ICD‐10 code) to define NAFLD, which may underestimate the accurate prevalence and incidence of NAFLD, as reflected by only 19,053 cases of NAFLD over 20 years 18 . The association between depression and NAFLD is well established, 13 as well as an association between advanced fibrosis in metabolic dysfunction‐associated fatty liver disease and depression 19 .…”

“…Several studies using biopsy‐proven NAFLD have also shown an association between depression and nonalcoholic steatohepatitis, 15 hepatocyte ballooning 16 and NAFLD activity score 17 . A recent study reported that major depressive disorder in patients with NAFLD was not independently associated with improved decompensated cirrhosis‐free survival, while survival rates among patients with NAFLD patients and co‐existing major depressive disorder were higher than those without major depressive disorder 18 . We examined whether depression among individuals with NAFLD clinically impacts all‐cause/cause‐specific mortality in a nationally representative general population from the United States.…”

Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry

“…The findings of substantial observational studies support the concept that MDD may increase the risks of GID (Fang et al, 2019; Kim et al, 2019; Martín-Merino, Ruigómez, García Rodríguez, Wallander, & Johansson, 2010). Despite the plausible positive association between MDD and GID, there is also partial evidence to support the claim is non-existent (Kim et al, 2013; Lee, Otgonsuren, Younoszai, Mir, & Younossi, 2013; Shaheen, Kaplan, Sharkey, Lethebe, & Swain, 2021). Observational studies yield inconsistent results, and the real direction of causal association cannot be ascertained owing to measurement error, confounding, and reverse causality bias (Fewell, Davey Smith, & Sterne, 2007).…”