Background: An association between multiple sclerosis (MS) and depression has been recognized for several decades and has attracted considerable attention in research. However, there are considerable gaps in the current state of knowledge. In this review, the literature concerned with: (1) the burden of depression in MS; (2) the etiology of depression in MS, and (3) the treatment of depression in MS are critically examined. Method: The literature review utilized Medline (1966–1996), and was supplemented by citations extracted from the papers originally uncovered. Results: Numerous studies have identified elevated depressive symptom scores in MS patients relative to nonclinical and (some) clinical control groups. Furthermore, studies of depressive disorders have clearly documented elevated prevalence rates in MS samples. The literature does not identify any specific pattern of neurological involvement as being consistently associated with depressive symptoms or disorders. Psychosocial risk factors contribute to the etiology of depression in MS, but the relative importance of various risk factors is yet to be determined. A single randomized controlled clinical trial, and additional anecdotal evidence, suggests that antidepressant pharmacotherapy is effective for depressive disorders in MS. Conclusions: Future epidemiological studies should not restrict their evaluation of risk factors to those specific factors that are closely related to the disease process. In particular, future researchers should resist the temptation to focus too exclusively on neuropathology. Biological, psychological and social risk factors are all potentially important. Additional empirical efforts to refine the various treatment approaches would be a welcome addition to this literature.

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