A study has found that patients with multiple sclerosis (MS) and depression are at greater risks of incident vascular disease and mortality than age-, sex-, and general practice-matched controls. The study also found that MS status and depression are synergistic in their effects on all-cause mortality, with 14% of effects observed being due to their interaction.

The results of the study, published in Neurology, showed that patients with MS, regardless of whether they had depression, were at increased risk of vascular disease compared to matched controls without depression. Over a 10-year period, the incidence of any macrovascular disease per 100,000 person-years was 0.66 (95% CI, 0.60-0.72) for controls without depression, compared to 1.17 (95% CI, 0.97-1.42) for MS patients without depression and 2.44 (95% CI, 1.89-3.14) for MS patients with depression. These values corresponded to hazard ratio (HR) values of 1.48 (95% CI, 1.23-1.74) and 3.30 (95% CI, 2.37-4.23) for MS patients without and with depression, respectively.

The risk of all-cause mortality was also higher in people with MS than in matched controls. Compared to controls without depression, MS patients without depression had an HR value of 3.88 (95% CI, 3.66-4.10) while patients with depression had an HR value of 5.43 (95% CI, 4.88-5.96). These ratios were in contrast to controls with depression, who had an HR value of 1.75 (95% CI, 1.59-1.91).

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Depression, whether in patients with MS or controls, was associated with a 2-fold increased risk of cardiovascular disease mortality as well. The association between cardiovascular disease and depression was not observed in men, however.

“Additional studies should be conducted to evaluate whether effectively treating depression in the MS population (perhaps with a lower threshold than those not affected by MS) reduces the risk of incident vascular disease and therefore reduces disability progression and mortality,” the authors suggested.

The retrospective study identified and analyzed information from 12,251 patients with MS and 72,572 matched controls between January 1, 1987, and September 30, 2018. Of these participants, 21% of patients with MS had depression at baseline compared to 9% of controls.


Palladino R, Chataway J, Majeed A, Marrie RA. Interface of multiple sclerosis, depression, vascular disease, and mortality: a population-based matched cohort study. Neurology. Published online September 1, 2021. doi:10.1212/WNL.0000000000012610