Background. Interferons are a class of cytokines profoundly affecting immune function. Several
interferons are now synthesized and used clinically, notably for viral diseases and cancer. In
addition to their desired immune effects, interferons cause a number of toxicities, including
prominent effects on the nervous system.
Methods. This literature review focused on the incidence of depression associated with interferon
treatment. Possible neurochemical mechanisms and remedial strategies were also considered.
Results. Interferon treatment, particularly with the alpha subtype, is unquestionably linked with
depression, but the strength of association is uncertain because of erratic ascertainment and pre-
treatment co-morbidity. A likely pathogenic mechanism has been described, involving interferon
suppression of serotonin synthesis. Controlled treatment trials of interferon-induced depression are
not yet available.
Conclusions. Neurotoxicity substantially limits the use of interferons. At least some of the risk of
depression appears to derive from their anti-serotonergic effects, consistent with the large body of
evidence pointing to a general link between serotonin and affective illness. Vigilant detection and
aggressive treatment of depression is necessary to optimize interferon treatment of many patients.