Neuropsychiatric complications of interferons: Classification, neurochemical bases, and management

Background. Recombinant interferons are widely used for a number of serious illnesses. However, their use is sometimes associated with severe and disabling neuropsychiatric side effects. Methods. A MEDLINE search identified pertinent laboratory investigations, case reports, clinical studies and letters published between 1983 and 2004 in the English language journals. The studies in which interferons were used in combination with other cytokines were excluded. Results. The interferon-associated neuropsychiatric side effects are divided into mood-related symptoms (depression/mania), cognitive impairment (including delirium), psychosis and isolated psychiatric symptoms. Putative neurotransmitters (serotonin and dopamine), hormones (cortisol) and cyokines (interleukin-2 and 6) have been implicated in the pathophysiology of these side effects. Management of neuropsychiatric side effects of interferons ranges from supportive measures, dose reduction, cessation of therapy and the use of appropriate psychotropic agents. Conclusions. Interferon-treated patients should be monitored for mental status changes. There are no controlled studies on pharmacological management of interferon-induced neuropsychiatric side effects. The use of interferons in patients with stable psychiatric disorders is not contraindicated. However, such patients should be closely monitored during the course of treatment with interferons.