RESUMEN
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.
Asunto(s)
Antidepresivos de Segunda Generación/uso terapéutico , Antineoplásicos/efectos adversos , Trastorno Depresivo/tratamiento farmacológico , Interferón-alfa/efectos adversos , Paroxetina/uso terapéutico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Trastorno Depresivo/inducido químicamente , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Proteínas Recombinantes , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
Although options for pharmacologic treatment for depression have grown seemingly exponentially over the past several decades, the current armamentarium of antidepressants continues to have limitations of both efficacy and tolerability. The problems include an unacceptable lack of efficacy, delayed onset of therapeutic effects, an inability to predict responses to one or another agent, drug-drug interactions, and difficulty with tolerability during both acute and chronic treatment. This article reviews the problems that persist in the use of currently available antidepressant medications and presents a list of attributes that would be characteristic of the ideal antidepressant.
