Can Treating Depression in Multiple Sclerosis Reduce Deaths?

People with multiple sclerosis (MS) and depression were more like to die over a 10-year period than people with neither condition, a population-based matched cohort study in England showed.

The 10-year hazard of all-cause mortality was more than five times greater in people with MS and depression (HR 5.43, 95% CI 4.88-5.96) than in people who had neither MS nor depression, reported Raffaele Palladino, MD, PhD, of Imperial College of London, and colleagues in Neurology.

MS patients, with or without depression, also had a greater risk of incident vascular disease.

For all-cause mortality, the joint effect of MS plus depression equaled more than the effect of each factor alone; 14% of the effect was attributable to the interaction between MS and depression.

“Depression and MS have a synergistic effect on all-cause mortality,” Palladino told MedPage Today. “Additional studies should be conducted to evaluate whether effectively treating depression in people with MS reduces vascular risk and therefore reduces disability progression and mortality.”

MS patients with both relapsing-remitting and progressive forms of the disease have an increased risk of depression.

“Depression is one of the most common comorbid conditions in prevalent multiple sclerosis cohorts and has been associated with lower quality of life and increased disability, and mortality in MS,” observed Amber Salter, PhD, of UT Southwestern Medical Center in Dallas, in an accompanying editorial.

“The consistency of the synergistic effect observed in this study and with that of a smaller, population-based Canadian study adds to the evidence of a possible biological interaction between MS and depression for mortality,” she wrote.

The retrospective study involved 12,251 MS patients and 72,572 matched controls from the Clinical Research Datalink database in England from 1987 to 2018. At baseline, 21% of MS patients and 9% of controls had a diagnosis of depression. In both groups, people with depression were more likely to be female and younger than people without depression.

People with MS had increased risk of incident vascular disease regardless of whether they had comorbid depression, compared with controls who had neither condition. This risk was highest in people who had both MS and depression (HR 3.30, 95% CI 2.37-4.23).

Incidence of all-cause mortality per 100,000 person-years was 10.30 (95% CI 9.17-11.57) for people with MS and depression, 10.58 (95% CI 9.99-11.21) for people with MS without depression, 3.59 (95% CI 3.18-4.05) for controls with depression, and 2.53 (95% CI 2.42-2.64) for controls without depression.

Depression in people with and without MS also was associated with a two-fold increased risk of cardiovascular disease mortality, compared with people who had neither condition. No interaction between MS status and depression on cardiovascular mortality or incident vascular disease was seen.

“To our knowledge, prior studies have not examined the association between depression and subsequent onset of vascular disease in MS,” Palladino and colleagues noted.

Earlier research has linked comorbid ischemic disease with an increased risk of incident depression in MS, the researchers pointed out. “Among people with rheumatoid arthritis, higher levels of depressive symptoms are also associated with increased odds of subclinical atherosclerosis,” they wrote. “Coupled with our findings, these prior studies suggest that bidirectional relationships exist between depression and vascular disease in MS.”

“The findings underscore the importance of identifying depression in people with MS, as well as monitoring for other risk factors for heart disease and stroke,” Palladino noted. A limitation of the study was that researchers lacked information about risk factors that may have influenced vascular disease and death, like BMI.