The prevalence and healthcare burden of psychiatric disorders in the 5 years leading up to a multiple sclerosis (MS) diagnosis suggested that psychiatric comorbidity may be a reasonable candidate to include in an MS prodrome, data from a case-control cohort study found.
The study looked at two groups of MS patients in the 5 years preceding the index date, which was determined either by a demyelinating claims event (the administrative cohort) or by a neurologic evaluation (the clinical cohort).
In the administrative cohort, the prevalence of psychiatric morbidity—depression, anxiety, bipolar disorder, or schizophrenia—was 28% in MS cases and 14.9% in controls (prevalence ratio, 1.91; 95% CI, 1.83-2.00) in the 5 years before the index date, reported Helen Tremlett, PhD, of the University of British Columbia in Vancouver, Canada, and co-authors.
In the clinical cohort, the prevalence of psychiatric comorbidity in the 5 years before the index date was 22% in MS cases and 14.1% controls (prevalence ratio, 1.58; 95% CI, 1.38-1.81), they wrote in Neurology.
"Together, these findings suggest that psychiatric morbidity constitutes a significant burden very early in the MS disease course and may be a feature of the MS prodrome," Tremlett and colleagues wrote.
"In both cohorts, the prevalence of psychiatric morbidity for patients with MS was higher than for controls in each of the 5 years before the index dates," they continued. "Moreover, these differences increased steadily as the index date approached."
Prior research has shown that people who go on to have MS steadily increased healthcare use at least 5 years before their first "classic" MS symptom or first demyelinating event, Tremlett and colleagues observed. Higher serum neurofilament light levels, indicating axonal damage, may be present up to 6 years before a first classical MS symptom, also supporting the concept of a MS prodrome.
Tremlett and co-authors used data from the administrative records of the province of British Columbia (administrative cohort), which includes virtually every health encounter for all residents, and the BC MS clinical database (clinical cohort), with data recorded by an MS neurologist during a routine visit to one of the province’s four MS clinics.
Cases were matched at index date by age, sex, and region with up to five controls without MS. The administrative cohort included 6,836 MS patients and 31,865 controls. The clinical cohort included 966 MS patients and 4,534 controls.
Mean age at onset for the administrative and clinical cohorts, respectively, was 44 and 37. Over 70% of both cohorts were women, and in the clinical cohort, over 90% of participants had relapsing onset MS.
"Differences in the index date definition for both cohorts explain the higher average age at the index date for the administrative relative to the clinical cohort," the authors noted. "We do not expect that age differences between cohorts played a role in this given that the prevalence of psychiatric disorders has not been shown to increase with age in the MS population."
In all 5 years prior to the index date, MS patients in the administrative group had significantly increased health care use compared with controls. Increases in health care use for the administrative group prior to the index date, compared with general population controls were, at 5 years prior (most remote) and 1 year prior (most recent), respectively:
Physician visits for any psychiatric comorbidity (78% and 124%).
Psychiatric visits (132% and 146%).
Psychiatric hospitalizations (128% and 197%).
Rate of psychotropic medication prescriptions (72% and 100%).
In the clinical group, these findings were not significantly different than the general population in many cases and confidence intervals were wide.
"Although some of the null findings in the clinical cohort might be attributable to sample size constraints, replicating this phenomenon in deeper phenotyped clinical cohorts is the path to refine whether these psychiatric symptoms are in fact a MS prodrome or if they are simply caused by the same demyelinating pathology that also cause a typical clinically isolated syndrome (CIS)," noted Raffaele Palladino, MD, PhD, of University Federico II of Naples, Italy, and the Imperial College of London, England, and Eva Strijbis, MD, PhD, of Vrije Universiteit Amsterdam in the Netherlands, in an accompanying editorial.
"With this paper, the authors have developed a robust methodology to identify the MS prodrome, and specifically the psychiatric morbidity," they added. "This approach should now be applied to different healthcare settings to improve generalizability and translate the results into clinical practice."
"No consensus has been reached on the recognition of psychiatric morbidity as a prodrome of MS," the editorialists pointed out. "In support of the hypothesis that this may not be linked to MS, there is the evidence that psychiatric symptoms are also common in the general population and better recognized by doctors in patients who also seek medical advice for neurological symptoms, and that psychiatric symptoms could be caused by the increased stress associated with MS-related prodromes/symptoms or the related process of navigating the health system."
Tremlett and co-authors acknowledged potential under- or over-estimation of the true burden of psychiatric morbidity during the MS prodrome: psychiatric case determinations in administrative data may have low sensitivity, possibly due to avoidance of care or stigma, or by inherently not including self-managed symptomatology.
"Equally, the psychiatric burden could be an overestimate due to surveillance bias as people in the prodromal phase interact more frequently with the health-care system, and therefore may present more opportunities to be diagnosed with a psychiatric disorder," they noted.
Sources:
Chertcoff AS, et al "Psychiatric comorbidity during the prodromal period in patients with multiple sclerosis" Neurology 2023; DOI: 10.1212/WNL.0000000000207843.
Palladino R, Strijbis, EM "How far are we in translating the multiple sclerosis prodromes in clinical practice?" Neurology 2023; DOI: 10.1212/WNL.0000000000207989