Background: Depression is among the commonest of psychiatric
disorders, and inflammatory mechanisms have been suggested to play a role in its
pathophysiology. Interferons are a superfamily of proinflammatory cytokines that
play a role in host defence mechanisms. Interferons are used in the treatment of a
variety of autoimmune (e.g. multiple sclerosis), viral (e.g. chronic hepatitis B and C),
and malignant (e.g. malignant melanoma, hairy cell leukemia) disorders; depression,
however, is a notable and clinically troublesome adverse effect.
Objective: This article seeks to present a simple explanation and update for the reader
about what interferons are, how interferons are classified, the clinical conditions in
which interferons are used, the occurrence of depression as a clinical adverse effect of
interferon therapy, possible mechanisms that explain interferon-related depression, the treatment of
interferon-related depression, and the prevention of interferon-related depression.
Methods: A qualitative literature review is presented.
Results and Conclusions: Irrespective of the indication for IFN therapy, IFNs are associated with a 30-
70% risk of treatment-emergent depression. This risk could be due to the IFN, or to an interaction
between the IFN and the indication for which it was prescribed. Various neurohormonal, neurochemical,
neurohistological, and other mechanisms have been put forth to explain IFN-related depression.
Prophylactic treatment with antidepressants reduces the risk of IFN-related depression; antidepressants
also effectively treat the condition. Recent alternatives to IFNs have shown to decrease the risk of