High Level of Psychiatric Morbidity in
Prodromal MS 

Pauline Anderson

February 27, 2023

SAN DIEGO — The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) vs controls in each of the 5 years prior to the onset of the disease, new research reveals.

Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS compared to their counterparts without the disease.

These results are an incentive to "keep exploring" to get a "clearer picture" of the MS prodrome, study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver, Canada, told Medscape Medical News.

With a better understanding of this phase, it might be possible to "push the limits to get an earlier diagnosis of MS," said Chertcoff.

The findings were presented here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023.

Psychiatric Comorbidities Common

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4534 controls.

The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study's primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. "In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset," said Chertcoff.

The analysis showed the relative risk (RR) of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% CI, 1.80 - 1.97) in the administrative cohort, and 1.57 (95% CI, 1.36 - 1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared to controls. This, said Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It's possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Chertcoff. He noted the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue and gastrointestinal issues during the MS prodrome, said Chertcoff.

Patients with MS are often seeing other physicians — including psychiatrists during the prodromal phase of the disease. Neurologists, Chertcoff said, could perhaps "raise awareness" among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson's disease.

When Does MS Start?

Commenting for Medscape Medical News, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director, Multiple Sclerosis Research Unit, Ottawa Hospital-General Campus, Canada, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled "one of the most compelling" recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms.

"You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms."

Results from this new study continue to beg the question of when MS actually starts, said Freedman.

The study received funding from the National MS Society in the US, the MS Society of Canada, and the Michael Smith Foundation for health research in BC. Chertoff and Freedman report no relevant financial relationships.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023. Abstract: Emerging Concepts Session S1.3. Presented February 23, 2023.

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