MS Treatments and Depression

SEATTLE — More potent disease-modifying therapies (DMTs) were linked to fewer depressive symptoms in relapsing-remitting multiple sclerosis (MS) patients than lower-efficacy treatments, interim results of an observational study presented here suggested.

Initiating a high-efficacy DMT was tied to a significant reduction in depression severity over about a year, reported Kathryn Fitzgerald, ScD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues, in a poster presentation at the annual Consortium of Multiple Sclerosis Centers meeting.

“We consider these results as preliminary, but they are consistent with some prior research studies that found a link between reduction in inflammation and downstream reduced depressive symptoms in non-MS populations,” Fitzgerald told MedPage Today.

Depression affects people with MS significantly: compared with controls, MS patients have shown an elevated annual prevalence ratio of depression of 1.77. An imaging study recently suggested that hippocampal neuroinflammation may play a role in depression-associated in MS. In addition, DMTs may affect depression etiology and symptomatology; some lower-efficacy DMTs like interferons many increase depression risk, while higher-efficacy DMTs may exert anti-depressive properties, Fitzgerald noted.

In this study, the team examined data from MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), an ongoing 10-site longitudinal study. The investigators used the Quality of Life in Neurological Disorders (Neuro-QoL) depression subscale, a self-reported measure, to assess depression severity.

The study population consisted of patients with relapsing-remitting MS who were new initiators of higher-efficacy or lower-efficacy DMTs and who completed at least two Neuro-QoL depression scales. Natalizumab (Tysabri), rituximab (Rituxan), ocrelizumab (Ocrevus), and alemtuzumab (Lemtrada) were considered higher-efficacy DMTs. Interferons, glatiramer acetate (Copaxone), fingolimod (Gilenya), and dimethyl fumarate (Tecfidera) were classified as lower-efficacy drugs.

The sample included 400 people in the higher-efficacy group and 530 in the lower-efficacy group. In both cohorts, 77% were women. The higher-efficacy group had a mean baseline age of 42.7; their baseline Neuro-QoL scores were an average of 46.3 points, and 43.3% had a history of antidepressant use or currently were taking antidepressant drugs. The baseline age in the lower-efficacy group was 46.8; this group had a baseline Neuro-QoL of 45.6 points, and 46.7% had used or were using antidepressants.

Over 1.06 years of follow-up, initiating higher-efficacy DMT was associated with a significant reduction in Neuro-QoL scores, while starting lower-efficacy drugs was not. Higher-efficacy treatment showed an average of 1.30 point per year reduction in depression severity (95% CI -2.24 to -0.37, P=0.006) in multivariable models. Lower-efficacy drugs were not associated with a change in depressive symptoms (mean change of 0.67, 95% CI -0.58 to 1.92, P=0.29).

The difference in slope over time was statistically different between the two groups (P=0.04). When interferons were excluded from the lower-efficacy group, the results were similar with a mean change of 0.65 (95% CI -0.61 to 1.92, P=0.31). Excluding interferons did not affect the slope difference (P=0.05).

“While we can’t draw definitive conclusions from this study — it’s an observational study and treatment class was not randomly assigned — it provides preliminary evidence of additional benefits of higher-efficacy disease-modifying therapy,” Fitzgerald said.

Analyses including further follow-up from this cohort are ongoing, she added: “We hope the final analyses will be completed by the fall.”