Paroxetine for the prevention of depression induced by high-dose interferon alfa

Background: Depression commonly complicates treatment with the cytokine int erferon alfa-2b. Laboratory animals pretreated with antidepressants have le ss severe depression-like symptoms after the administration of a cytokine. We sought to determine whether a similar strategy would be effective in hum ans. 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 plac ebo. The treatment was begun 2 weeks before the initiation of interferon al fa and continued for the first 12 weeks of interferon alfa therapy. Results: During the first 12 weeks of interferon alfa therapy, symptoms con sistent 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 gr oup (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 pe rcent), as compared with 7 patients in the placebo group (35 percent) (rela tive risk, 0.14; 95 percent confidence interval, 0.05 to 0.85). The inciden ce of adverse events was similar in the two groups. Conclusions: In patients with malignant melanoma, pretreatment with paroxet ine appears to be an effective strategy for minimizing depression induced b y interferon alfa. (N Engl J Med 2001;344:961-6.) Copyright (C) 2001 Massac husetts Medical Society.