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Background: Depression commonly complicates treatment with the cytokine interferon alfa-2b. Laboratory animals pretreated with antidepressants have less severe depression-like symptoms after the administration of a cytokine. We sought to determine whether a similar strategy would be effective in humans. Methods: In a double-blind study of 40 patients with malignant melanoma who were eligible for high-dose interferon alfa therapy, we randomly assigned 20 patients to receive the antidepressant paroxetine and 20 to receive placebo. The treatment was begun 2 weeks before the initiation of interferon alfa and continued for the first 12 weeks of interferon alfa therapy. Results: During the first 12 weeks of interferon alfa therapy, symptoms consistent with a diagnosis of major depression developed in 2 of 18 patients in the paroxetine group (11 percent) and 9 of 20 patients in the placebo group (45 percent) (relative risk, 0.24; 95 percent confidence interval, 0.08 to 0.93). Severe depression necessitated the discontinuation of interferon alfa before 12 weeks in 1 of the 20 patients in the paroxetine group (5 percent), as compared with 7 patients in the placebo group (35 percent) (relative risk, 0.14; 95 percent confidence interval, 0.05 to 0.85). The incidence of adverse events was similar in the two groups. Conclusions: In patients with malignant melanoma, pretreatment with paroxetine appears to be an effective strategy for minimizing depression induced by interferon alfa. (N Engl J Med 2001;344:961-6.) [ABSTRACT FROM AUTHOR]

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-α (IFN-α) 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-α therapy.Forty patients with malignant melanoma eligible for IFN-α 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-α 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 within two weeks of IFN-α therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-α 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-α, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced “sickness behavior.” [Copyright &y& Elsevier]