Connecting MS, Depression, Vascular Disease and Mortality

By Daniel K. Brantley
Wednesday, February 2, 2022

New retrospective research indicates depression management may lower mortality rates among those with MS.

Affecting 23.7% of individuals with multiple sclerosis (MS), depression is the most frequent MS comorbidity. This presents a particular danger, as depression is associated with poorer health behaviors — diet, physical activity and cardiovascular risk management — which can negatively affect MS and other aspects of health. It is therefore important to assess whether the association between depression, vascular disease and mortality differs in people with MS as compared with the general population.

A group led by Raffaele Palladino, MD, PhD, FFPH, of the Imperial College of London, undertook research to that end. According to Dr. Palladino, certain results were clear.

“[W]e found that people with MS who also have depression have increased risks of incident vascular disease and mortality,” he says. “Depression and MS have a synergistic effect on all-cause mortality.”

Understanding the Findings

Dr. Palladino’s population-based retrospective matched cohort study accounted for individuals with MS from England and their matched, non-MS controls. Drawing from patient data from Jan. 1, 1987 through Sept. 30, 2018, 84,823 individuals were studied, 12,251 of whom had MS, for a ratio of nearly six controls per MS patient. Of these, 21% (MS) and 9% (control) had baseline depression.

Depression among the control group led to a 10-year mortality that was 1.75 times greater than their non-depressed peers. All-cause 10-year mortality among those with MS was found to be 3.88 times greater with MS alone and 5.43 times greater in those with MS and depression. This MS-depression synergy was responsible for 14% of the observed effect on mortality. Depression was more common among young individuals and women within both cohorts.

“[The] association between mortality and depression in individuals with MS . . . is not surprising,” says Mark Skeen, MD, a board-certified neurologist at Duke University who focuses on MS and related inflammatory conditions of the brain. “These findings reinforce the importance of screening MS patients for depression, [as] recognizing and addressing depression in MS patients may have as much or more impact on quality of life and mortality as treating the disease itself.”

While the link between MS, depression and mortality gained confirmation, the specific relationship with vascular disease remains unclear. According to this retrospective study, those with MS were more likely to experience vascular disease, regardless of depression status. The highest incidence of vascular disease occurred among those with MS and depression (2.44 out of 100,000 person-years, compared to 1.17 with MS who are not depressed and 0.66 and 1.34 of controls without and with depression, respectively).

A difference was also found between the sexes. Whereas female MS patients with depression had higher incidence of vascular disease than non-depressed female MS patients, there was no difference among men regarding acute coronary syndrome or composite macrovascular disease risk.

There also was no increase of cardiovascular mortality among depressed men with MS. Dr. Palladino was not surprised by this. He stated that this finding “might be partially explained by the fact that the underlying vascular risk for men is higher than women.” He viewed this information as “adding to the evidence on sex-related differences in vascular mortality.”

Applying the Findings

Traditional risk factors for vascular disease include hypertension, smoking and diabetes. The results of this study indicate that a new approach to MS care may be appropriate. Depression screening may need to play a larger role in a patient’s journey.

“Depression and vascular disease may make MS even more disabling,” says Dr. Skeen. “Optimal MS care includes addressing all aspects of our patients’ lives.”

By screening for depression, there is potential to improve quality of life and lower mortality among the population with MS. This is good news, according to Kalina Sanders, MD, board-certified neurologist at Baptist Health in Jacksonville, Fla.

A specialist in MS and spasticity management, Dr. Sanders understood that depression and vascular disease increase mortality risk independently. She suspected the combination would increase that risk. Yet she was unaware of the magnitude of depression’s effect on MS patients.

This new insight has led Dr. Sanders to applaud the study’s findings, with some reservation.

“Although it is a robust data set, the population evaluated . . . was predominately Caucasian and from one geographic location. Therefore,” she says, “caution should be advised in extrapolating this data to a more diverse population that may have differing risks.”

While the study findings warrant caution, the connection between MS and depression is well established. Providers therefore ought not disregard this association and allow depression to go undiagnosed and unmanaged. Rather, these specialists believe providers ought to administer mental health screenings in an effort to provide all-around care for the MS patient.

Will such vigilance lead to reduced mortality risk? Dr. Palladino suspects it likely will, “but,” he says, “this must be confirmed by longitudinal data.”

Even if it does not impact mortality, Dr. Skeen sees the benefit, stating that “depression is one of the most common and disabling symptoms in MS, and it is therefore important to better identify individuals with depression and optimally care for them.”

The impact of treating depression on mortality among MS patients isn’t all that needs additional research. Vascular risk among the MS population also warrants further investigation to determine whether the associations are coincidental or causal. As research continues, clinicians may choose to prioritize assessing vascular risk among their patients with MS.