Choice of Disease Modifying Therapy May Impact Depression Risk for Multiple Sclerosis

Choice of disease modifying therapy for patients with multiple sclerosis (MS) is associated with a risk of depression, according to new research published in Multiple Sclerosis Journal.

“The stress reaction of receiving an MS diagnosis may contribute to the elevated risk of depression diagnosis and antidepressant use,” wrote Elsa Longinetti, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, and co-researchers. “Other evidence suggests an association between depression and risk of subsequent MS diagnosis, not attributable to genetic liability.”

It is known that depression and antidepressant use are more common among patients with multiple sclerosis than the general population, but it’s unclear if treatment choice impacts risk.

Researchers aimed to determine if the choice of disease modifying therapy in patients with MS impacted risk of a depression diagnosis or use of antidepressants, as well as to determine if depression or antidepressant use caused treatment discontinuation and MS relapses.

This large nationwide Sweden-based cohort study was comprised of patients with relapsing remitting MS and no history of depression prior to use of a disease modifying therapy. Researchers used the Swedish MS Registry, a collection of healthcare data on patients with MS in Sweden, to examine patients living in Sweden at least 5 years prior to MS diagnosis, who were diagnosed with relapsing remitting MS between January 2010 and September 2018.

A total of 3803 patients with relapsing remitting MS were included for a period of 8 years, or until death, withdrawal from the registry, or migration out of Sweden.

Clinical diagnosis of depression was classified using ICD-10 codes F32-34 or F38-39, and patients were considered antidepressant users if they received at least two antidepressant prescriptions.

Observed antidepressants used by the cohort included but were not limited to selective serotonin reuptake inhibitors, non-selective monoamine oxidase inhibitors, and MAO A inhibitors.

Disease modifying therapies observed in the study included imethyl fumarate, fingolimod, glatiramer acetate, natalizumab, or rituximab, among others.

A lower risk of being diagnosed with depression or being prescribed antidepressants was observed in patients treated with rituximab.

Researchers noted patients with depression treated with interferons discontinued medication at a higher frequency than patients without depression, and patients taking antidepressants were more likely to discontinue using fingolimod as a disease modifying therapy compared to patients who were not on antidepressants.

However, the overall risk of disease modifying therapy discontinuation did not differ by depression or antidepressant use, nor did the overall risk of relapse.

Researchers highlighted rituximab in particular warrants further research into why patients may be at a lower risk of depression, noting the dosing schedule is different from other therapy options, but a true protective effect could improve its efficacy and tolerability profile for treatment of MS.

“Our results indicate that the choice of [disease modifying therapy] DMT is associated with subsequent risk of depression in MS, but further studies are needed to establish whether there is a causal link,” Longinetti et al concluded. “Overall, depression and use of antidepressants displayed limited associations with DMT discontinuation and MS relapse.”

—Erin McGuinness

Longinetti E, Frisell T, Englund S, Reutfors J, Fang F, Piehl F. Risk of depression in multiple sclerosis across disease-modifying therapies [published online ahead of print, 2021 Jul 15]. Mult Scler. 2021;13524585211031128. doi:10.1177/13524585211031128