Depression-free after Interferon-α exposure indicates less incidence of depressive disorder: A longitudinal study in Taiwan

Brain Behav Immun. 2020 Aug:88:125-131. doi: 10.1016/j.bbi.2020.05.044. Epub 2020 May 17.


Background: IFN-α-induced depression in patients undergoing hepatitis C virus (HCV) treatment provides powerful support for the inflammation hypothesis of depression. Most studies have focused on the occurrence of depressive symptoms, but there has been no study yet in depression-free HCV patients receiving IFN-α. We hypothesized that HCV patients who did not develop depression after IFN-α exposure might have a lower incidence of depressive disorders after the IFN-α treatment.

Methods: We conducted a twelve-year population-based cohort study of chronic HCV patients who received IFN-α therapy. The data were obtained from the Taiwan National Health Insurance Research Database. The study cohort was patients without any depressive disorder nor antidepressant use before and during IFN-α therapy. They were matched randomly by age, sex income and urbanization at a ratio of 1:4 with the control cohort of HCV patients without IFN-α therapy. The follow-up started after the last administration of IFN-α, and the primary outcome was the incidence of depressive disorders after IFN-α therapy.

Results: A total of 20,468 depression-free subjects were identified from records of HCV patients receiving IFN-α therapy. Patients without IFN-α-induced depression were associated with a significantly lower incidence (per 10,000 person-years) of new-onset depressive disorders (126.8, 95% Confidential Interval [CI] of 118.5-135.6) as compared to the control cohort (145.2, 95% CI of 140.0-150.6) (p < 0.001). After adjusting for age, sex, income, urbanization and comorbid diseases, the crude hazard ratio for the incident depressive disorder was 0.87 (95% CI, 0.80-0.87) and the adjusted hazard ratios was 0.79 (95% CI, 0.72-0.87) for IFN-α-induced depression-free subjects as compared to the controls.

Discussion: Our study indicates that IFN-α treated depression-free patients have a lower risk for depressive disorders. This hypothesized mechanism might derive from an IFN-α-induced resilience factor as yet to be defined.

Conclusions: Our study might suggest a new possibility for a new pharmacological strategy against depression.

Keywords: Depression-free; HCV; IFN-α-induced depression; Population-based retrospective cohort study in Taiwan; Prophylactic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • Cohort Studies
  • Depressive Disorder* / epidemiology
  • Humans
  • Incidence
  • Interferon-alpha* / adverse effects
  • Longitudinal Studies
  • Taiwan / epidemiology


  • Antiviral Agents
  • Interferon-alpha