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Neurobehavioral effects of interferon-a in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.

Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CF, Miller AH.
Neurobehavioral effects of interferon-a in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.
Neuropsychopharmacology 26:643-652, 2002.

Summary

This study was conducted by CDC collaborators at Emory University who are conducting studies of immune stimulation and CFS. Interferon-a is a cytokine released early during viral infection, has a variety of effects on the immune system, and is used therapeutically to treat a variety of chronic viral infections and malignant disorders. Therapeutic administration of interferon-a is often accompanied by side effects that include fatigue, cognitive impairment, altered sleep, pain, and depression. These are the symptoms of CFS and CDC is partly funding and collaborating in their studies of interferon-a as a "model" of CFS. This study showed that fatigue, sleep abnormalities, and musculoskeletal pain appeared early following interferon-a therapy but cognitive dysfunction and depressed mood appeared considerably later. It also showed that while depression and cognitive complaints responded to the antidepressant paroxetine, fatigue and disturbed sleep did not. In the context of immune activation the core symptoms of CFS have a different natural history and treatment response than do core symptoms of major depression. Identification of specific cytokines and cytokine pathways involved in fatigue may allow identification of potential treatment targets and pathways for further exploration in CFS patient samples.

Abstract

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-a (IFN-a) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-a therapy.

Forty patients with malignant melanoma eligible for IFN-a treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-a therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale.

Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared with two weeks of IFN-a therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-a treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-a, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."

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