Drug side effects are commonly listed among the causes of depression, and the mechanisms linking depression with medical illness. Although depression is listed as a side effect of a number of diverse agents, the evidence demonstrating that they cause depression is, at best, limited. Moreover, ongoing research on the psychiatric side effects of interferon-alpha and other agents has suggested a new paradigm: instead of avoiding medications that can cause affective toxicity in potentially vulnerable patients, it may be useful to think in terms of preventive strategies that may help them tolerate and benefit from treatments that may be medically necessary. In this evolving context, it is a useful time to review the issue of depression as a drug side effect, to evaluate the evidence base, to consider the nature of the symptoms and syndromes that may result, to discuss methods for investigating this problem, and to present evolving findings on medications including simvastatin, naproxen, and metoclopramide.
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