BACKGROUND The use of a high dose regimen of interferon‐alpha‐2b (IFN) has recently been demonstrated to benefit patients with resected high risk melanoma. The incidence of melanoma is rising rapidly, and the use of this regimen is becoming increasingly common. IFN has been associated with numerous psychiatric side effects. METHODS The authors describe four melanoma patients treated with adjuvant IFN who developed a manic‐depressive syndrome or mood instability with therapy, and they review the literature on mania and the mixed affective syndromes associated with IFN. RESULTS The authors suggest that IFN may induce a mixed affective instability, and that patients risk developing hypomania or mania as IFN doses fluctuate or as IFN‐induced depression is treated with antidepressants alone. Mania is particularly associated with dose reductions or pauses in IFN treatment. The risk of mood fluctuation continues after treatment with IFN stops, and patients should be monitored for 6 months following completion of therapy. Gabapentin appeared effective as monotherapy for acute mania, as an antianxiety agent, as a hypnotic, and as a mood stabilizer in these individual cases. CONCLUSIONS Mania and mood instability can occur in patients being treated with IFN therapy for melanoma. In this study, gabapentin was an effective mood‐stabilizing agent for these patients. Cancer 2000;89:356–62. © 2000 American Cancer Society.

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