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The link between multiple sclerosis and depression

Key Points

  • Depression is more common in patients with multiple sclerosis (MS) than in the general population, and substantially impairs quality of life; suicide rates are also elevated in patients with MS

  • To advance research and clinical practice, depression in patients with MS will require a rigorous definition based on quantitative assessment

  • Structural brain changes on MRI account for almost 50% of the variance in the presence of MS-related depression; genetic, biochemical, immunological and psychosocial factors have also been implicated

  • Current disease-modifying therapies for MS do not seem to cause mood disorders

  • Treatment of MS-related depression requires further investigation: antidepressants are modestly effective, but adverse effects can preclude adequate dosing; cognitive–behavioural therapy is also effective

  • Randomized trials must address whether combining treatments improves outcomes


Depression—be it a formal diagnosis based on consensus clinical criteria, or a collection of symptoms revealed by a self-report rating scale—is common in patients with multiple sclerosis (MS) and adds substantially to the morbidity and mortality associated with this disease. This Review discusses the prevalence and epidemiology of depression in patients with MS, before covering aetiological factors, including genetics, brain pathology, immunological changes, dysregulation of the hypothalamic–pituitary–adrenal axis, and psychosocial influences. Treatment options such as antidepressant drugs, cognitive–behavioural therapy, mindfulness-based therapy, exercise and electroconvulsive therapy are also reviewed in the context of MS-related depression. Frequent comorbid conditions, namely pain, fatigue, anxiety, cognitive dysfunction and alcohol use, are also summarized. The article then explores three key challenges facing researchers and clinicians: what is the optimal way to define depression in the context of diseases such as MS, in which the psychiatric and neurological symptoms overlap; how can current knowledge about the biological and psychological underpinnings of MS-related depression be used to boost the validity of this construct; and can intervention be made more effective through use of combination therapies with additive or synergistic effects, which might exceed the modest benefits derived from their individual components?

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The authors wish to acknowledge the support of the endMS Network and the Multiple Sclerosis Society of Canada.

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All authors contributed equally to researching data for the article, developing the discussions of its content, writing the article, and reviewing and editing the manuscript before submission.

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Correspondence to Anthony Feinstein.

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Competing interests

A.F. has received honoraria from Biogen, Merck Serono, Novartis and Teva. The other authors declare no competing interests.

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Feinstein, A., Magalhaes, S., Richard, JF. et al. The link between multiple sclerosis and depression. Nat Rev Neurol 10, 507–517 (2014).

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