Neuropsychiatric side effects of interferon-alfa therapy.
OBJECTIVE
Immunotherapy with interferon-alfa (IFN-alfa) is used in a variety of diseases in- and outside clinical trials (e.g., chronic hepatitis, melanoma, chronic myelogenous leukemia, renal cell carcinoma, multiple myeloma). Treatment with IFN-alfa can cause (severe) neuropsychiatric side effects. The purpose of this article is to give an updated review of data on the incidence, manifestations and prediction of psychiatric side effects of immunotherapy with IFN-alfa. Furthermore, the article gives an overview of the management strategies and of the various theories on the pathophysiology of behavioural effects induced by cytokines.


METHODS
Use was made of computerized searches and of checking cross-references of articles and book chapters. The data on the incidence, manifestations and prediction are arranged by source of information, by target symptoms and by method of ascertainment.


RESULTS
Different sources of information exist, e.g. adverse event reports of clinical trials, case descriptions and research specifically targeted on neuropsychiatric side effects. IFN-alfa is capable of inducing depressive symptoms and syndromes; the evidence for the induction of other psychiatric side effects is weaker. The depressive syndromes induced by IFN-alfa are in need of a more precise characterization. The results of studies on prediction of side effects are contradictory. Guidelines on managing psychiatric side effects predominantly arise from practical experience and common sense. Patient education plays a pivotal role. At this moment, there is no comprehensive theory on the pathophysiology of cytokine-induced psychiatric side effects.


CONCLUSIONS
There is sufficient empirical support for a causal relation between IFN-alfa and the development of depressive symptoms and syndromes. Practical management of neuropsychiatric side effects begins before the start of therapy and should consist of repeated patient education, drug treatment and supportive measures. There are diverging theories on the pathophysiological backgrounds.
Van Gool
Arthur R
AR
Department of Psychosocial Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. gool@onch.azr.nl
Kruit
Wim H J
WH
Engels
Frederike K
FK
Stoter
Gerrit
G
Bannink
Marjolein
M
Eggermont
Alexander M M
AM
D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000139:chemically induced / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001523:Mental Disorders / Q000139:chemically induced* / Q000523:psychology; D013577:Syndrome
D007155:Immunologic Factors; D016898:Interferon-alpha