Review articleBiological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review

- Systematic review of biological mechanisms of IFN-α induced depression is proposed.
- Stringent inclusion criteria enable an accurate assessment of available evidence.
- Several mechanisms may be implicated to the emergence of IFN-α induced depression.
- There is a lack of replicated evidence on such biological mechanisms.
- The mechanisms involved in IFN-α induced depression in humans remain unclear.

BackgroundA significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV.MethodsMajor electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint.ResultsEight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression.LimitationsA meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence.ConclusionsThis systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.