The impact of depression and antidepressant usage on primary biliary cholangitis clinical outcomes

PLoS One. 2018 Apr 4;13(4):e0194839. doi: 10.1371/journal.pone.0194839. eCollection 2018.

Abstract

Background: Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients.

Methods: We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA).

Results: We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07-0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05-0.83).

Conclusions: In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antidepressive Agents / therapeutic use*
  • Bile Ducts / pathology*
  • Cholagogues and Choleretics / therapeutic use
  • Cholangitis / complications
  • Cholangitis / diagnosis*
  • Cholangitis / drug therapy
  • Cholangitis / mortality
  • Cohort Studies
  • Databases, Factual
  • Depression / complications
  • Depression / diagnosis
  • Depression / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Liver Cirrhosis / etiology
  • Liver Transplantation
  • Male
  • Mianserin / analogs & derivatives
  • Mianserin / therapeutic use
  • Middle Aged
  • Mirtazapine
  • Proportional Hazards Models
  • Treatment Outcome
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Antidepressive Agents
  • Cholagogues and Choleretics
  • Mianserin
  • Ursodeoxycholic Acid
  • Mirtazapine

Grants and funding

This work was funded through a Canadian Institutes of Health Research Team Grant (M. Swain as PI). Grant title: Health Challenges in Chronic Inflammation Initiative. Grant ID: THC – 135231.