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Interferon-α-Induced Depression: When a Randomized Trial Is Not a Randomized Controlled Trial

Patten and Barbui [1] have performed a singular service to the profession by carrying out a systematic review on drug-induced depression. Their recommendations are based on studies that have randomly allocated patients into study and control groups, and the authors have provided an adequate justifi cation for this being the most scientifi c approach. This letter is to point out that the authors have erroneously designated a study as a randomized controlled trial. The authors state that Malaguarnera et al. [2] randomly assigned hepatitis C patients to three treatment groups receiving interferonand a control group [1 , p. 211]. I believe that this is based on a misreading of the paper or relying on the abstract. A closer reading of the paper reveals that the patients were randomized to four treatment groups, receiving recombinant interferon2a, recombinant interferon2b, lymphoblastoid interferonand leukocyte interferon, respectively. The control group consisted of 18 untreated hepatitis C patients who were not randomly assigned. Thus, this study is not a randomized trial that can answer the question posed by Patten and Barbui [1] . As the study by Malaguarnera et al. was the only randomized trial identifi ed by the authors in the area of interferon-induced depression, the exclusion of this study would mean that interferonno longer appears in column 2 of table 2 [1 , p. 212]. Until randomized controlled trials become available, practising clinicians will have to rely on narrative reviews of observational studies [3] to inform their decision making. As systematic reviews lie high on the evidence hierarchy and are relied on by practitioners and policy makers, one expects reviewers to be more rigorous in their reading of the papers. This is the least we can expect of distinguished authorities on iatrogenic depression (Patten) and research methodology (Barbui).