Can antidepressants prevent interferon-alpha-induced depression? A review of the literature Amanda Galvão-de Almeida, M.D. a,b, ⁎ , Camila Guindalini, Ph.D. b,c , Susana Batista-Neves, M.D., M.Sc. a , Irismar R. de Oliveira, M.D., Ph.D. a , Ângela Miranda-Scippa, M.D., Ph.D. a , Lucas C. Quarantini, M.D., Ph.D. a a Universidade Federal da Bahia, Teaching Hospital-Psychiatry Service, 40110-909 Bahia, Brazil b Universidade Federal de São Paulo, Department of Psychiatry and Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), 04026-001 São Paulo, Brazil c Universidade Federal de São Paulo, Department of Psychobiology, 04023-062 São Paulo, Brazil Received 20 October 2009; accepted 2 March 2010 Abstract Objective: To review the literature about the efficacy of antidepressant prophylaxis during interferon-alpha (IFN-α) therapy. Method: We have performed a database search in PUBMED and ISI Web of Knowledge (1980–August 2009) for the available literature. The keywords “prevention” or “prophylaxis”, and “depression”, and “interferon”, and “antidepressant” or “antidepressive agents” were used. Results: The six eligible studies comprise three randomized controlled trials, two in hepatitis C virus (HCV) patients and one in individuals with melanoma, and three open-label studies with HCV patients. The results of the randomized controlled trials suggest that antidepressant prophylaxis may blunt the magnitude of depressive symptoms in HCV patients and raise the rates of treatment completion. In melanoma patients, this preventive strategy may reduce the incidence of depression during IFN-α treatment. In addition, the open-label studies with HCV patients suggest that this strategy may reduce the onset of major depression in specific samples (current psychiatric diagnosis, major depression in remission, past history of IFN-α-induced depression) on IFN-α (re-)treatment. Conclusions: In the face of so few trials about the usefulness of prophylaxis with antidepressants before IFN-α treatment, there is not enough information to sufficiently and widely support this strategy to prevent depression. However, this approach may, nonetheless, bring some beneficial outcomes, if applied to specific patient groups. © 2010 Elsevier Inc. All rights reserved. Keywords: Major depression; Interferon-alpha; Prevention; Antidepressant; Review 1. Introduction Interferon-alpha (IFN-α), conventional or pegylated (PEG), in combination with ribavirin (RBV), constitutes the only Food and Drug Administration-approved treatment for chronic hepatitis C virus (HCV) infection, a disease that affects over 170 million individuals worldwide [1–5]. Moreover, IFN-α is the current approved adjuvant treatment for melanoma [6,7]. Despite its potential therapeutic benefits, administration of IFN-α frequently prompts the appearance of neuropsy- chiatric symptoms, e.g., depressed mood, anxiety, psychosis, suicidal behavior, and acute dystonia, as well as neurove- getative and somatic symptoms, e.g., anorexia, psychomotor slowing, and altered sleep [3,8–10]. Clinical studies have shown that approximately 30–45% of patients receiving IFN-α develop a major depression episode (MDE) that may lead to severe outcomes, such as suicidal behavior during the course of the therapy [1,3]. Additionally, IFN-α-induced MDE limits IFN-α therapeutic potential by compromising compliance, and leading to dose reduction or interruption of the therapy [1]. However, in spite of the IFN-α-related side- effects cited, this cytokine represents an opportunity for Available online at www.sciencedirect.com General Hospital Psychiatry 32 (2010) 401 – 405 ⁎ Corresponding author. Hospital Universitário Professor Edgard Santos, Serviço de Psiquiatria, 3°. Andar/40110-909. Salvador, BA, Brazil. Tel.: +55 71 3351 4111; fax: +55 11 3351 4111. E-mail address: amandacgalvao@yahoo.com.br (A.G. Almeida). 0163-8343/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2010.03.001