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Comorbidities in MS Found to Increase Psychological Problems

ARTICLE IN BRIEF

The physical symptoms of multiple sclerosis can worsen symptoms of depression, anxiety, and fatigue in multiple sclerosis, affecting health-related quality of life, according to a new study.

Canadian researchers have found that multiple sclerosis (MS) patients with other physical health issues also are more prone to depression, anxiety, or fatigue, all of which appear to significantly impair their quality of life.

Investigators at four sites across Canada examined demographic and clinical information from medical records of 949 MS patients. They assessed physical and mental comorbidities, fatigue and health-related quality of life, or HRQoL, using questionnaires, such as the Health Utilities Index Mark 3 (HUI3).

The investigators also examined when MS symptoms first appeared, their clinical course, and demographic data for each participant. They found that 63 percent of patients had HRQoL scores reflecting severe disability.

In terms of comorbidities, 57 percent of patients had at least one other physical illness, 39 percent had clinically meaningful anxiety symptoms, and 21 percent had clinically meaningful depression symptoms. The most common physical comorbidities were hypertension (17.8 percent), migraine (17.3 percent), and hypercholesterolemia (12.4 percent).

The findings were published in the March 9 online issue of Neurology.

“While few studies have explored the relationships that we observed, support for our findings does exist,” said lead author Lindsay Berrigan, PhD, assistant professor of psychology at St. Francis Xavier University.

“We looked at a large range of patients at different stages of progression. While 72 percent had relapsing-remitting MS, we were not specifically focusing on relapsing-remitting disease. But this rate is consistent with rates from other clinic-based studies,” she told Neurology Today in a telephone interview.

She added that in addition to treatments aimed at reducing disability, more active screening and treatment of physical and mental comorbidities could lead to meaningful improvement in HRQoL, and that the findings demonstrate the importance of greater awareness of the potential effects of physical comorbidity and the risk of mental problems in clinical practice.

“Our results suggest that although the direct influence on HRQoL is in general modest, physical comorbidities can worsen symptoms of depression, anxiety, and fatigue in MS, thereby indirectly influencing HRQoL.”

When multiple influences on HRQoL in MS patients have been examined by other researchers, depression is often one of the most, if not the most important, predictor of reduced scores. However, the association between physical problems and mental issues has not been well studied, she noted.

“Moreover, other research has found that anxiety disorder is considerably more prevalent in MS patients but infrequently recognized, and that only about 12 percent of patients ever seek or receive such a diagnosis.”

The degree of each patient's disability most strongly affected their quality of life. The data indicate that the relationship of both physical comorbidities and anxiety with HRQoL is predominantly indirect, emerging when their influence on other variables such as depression and fatigue were also factored in. The relationship between depression and HRQoL is almost equally split between direct and indirect associations, according to Dr. Berrigan.

“While the influence of comorbid depression problems may be at least partially mediated by their influence on symptoms of fatigue, it could be argued that the fatigue may also contribute to depression, as opposed to depression influencing fatigue,” she explained. “The participants in this study are being followed up over time, and we plan to conduct longitudinal analyses that will help to better clarify the nature of the relationships we found.”

One limitation of the study was that the investigators relied on patient reports of their comorbidities rather than clinical diagnoses, although the questionnaire they used has been validated in the past against medical records and self-reported comorbidity associated with HRQoL.

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DR. LINDSAY BERRIGAN: “While the influence of comorbid depression problems may be at least partially mediated by their influence on symptoms of fatigue, it could be argued that the fatigue may also contribute to depression, as opposed to depression influencing fatigue. The participants in this study are being followed up over time, and we plan to conduct longitudinal analyses that will help to better clarify the nature of the relationships we found.”

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DR. DAVID E. JONES: “More studies are clearly needed, but we have no doubt that depression affects patients quality of life. The question is whether other confounding factors are involved and to what extent treatment of comorbid psychological problems will improve HrQoL. While psychiatric comorbidities may be attributed to MS, there is little evidence that disease-modifying therapies can improve these in MS patients.”

AAN GUIDELINE

A 2014 evidence-based guideline issued by the AAN also found a significant lack of quality research on psychiatric disorders among MS patients, and whether or not drugs or other non-pharmaceutical approaches for anxiety and depression are effective or appropriate.

Nonetheless, the special panel's review of medical literature from 1950 through 2011, said several options may help clinicians in making diagnoses.

The guideline suggested considering the Beck Depression Inventory and a two-question tool to screen for depressive disorders, and the General Health Questionnaire to screen for more broadly defined emotional disturbances. In addition, the Center for Neurologic Study Emotional Lability Scale may be helpful in screening pseudobulbar affect, characterized by seemingly random and uncontrollable episodes of crying, laughter, or other emotional outbursts.

The AAN panel concluded that there is too little evidence to support or refute the use of other screening tools, largely because somatic/neurovegetative symptoms can affect their accuracy. Diagnostic instruments and most clinical evaluation procedures for identifying psychiatric disorders in MS also lacked sufficient evidence.

For depressive symptoms clinicians may consider a telephone-administered cognitive behavioral therapy program, and although drug and nonpharmacological therapies are widely used to treat anxiety and depression in MS patients, there is too little evidence to support or refute using antidepressants or individual or group therapies, according to the AAN guidelines.

EXPERTS COMMENT

David E. Jones, MD, chair of the AAN Multiple Sclerosis Section and Assistant Professor of Neurology at the University of Virginia James Q. Miller Multiple Sclerosis Clinic in Charlottesville, told Neurology Today that MS clinicians should take a broader approach with MS patients than simply focusing on the disease.

“I think that for years, many patients with MS have been disappointed that they are seen just as having MS, instead of being seen as a whole person. There has been an unfortunate disregard for comorbidities, at least in part because MS clinicians are primarily focused on MS-modifying therapies, rather than also looking for seemingly unrelated symptoms their patients might also be experiencing.”

It's not just the fault of clinicians however, he said in an interview. Both they and MS patients may be reluctant to discuss and/or acknowledge depression.

He also noted that because of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), reimbursement for health care is shifting from a fee-for-service payment system to one focused on the quality of care, likely based on patient outcomes.

“This is problematic because there is so little research on the benefit of treating these comorbidities in MS. I think this study suggests that we may be able to improve patient outcomes by focusing more on comorbidities. Depression was shown to be a very common comorbidity affecting HRQoL in this paper, yet it remains under-recognized and undertreated in clinical practice,” he told Neurology Today.

“More studies are clearly needed, but we have no doubt that depression affects patients' quality of life. The question is whether other confounding factors are involved and to what extent treatment of comorbid psychological problems will improve HrQoL. While psychiatric comorbidities may be attributed to MS, there is little evidence that disease-modifying therapies can improve these in MS patients.”

Despite advances in clinicians' recognition that emotional disorders are common in MS, such disorders are often undetected and inadequately treated, according to the 2014 analysis.

“Studies that could improve detection, diagnosis, and treatment practices include better evidence for screening and diagnosis, including direct comparisons of screening tools and diagnostic instruments for assessing symptoms of anxiety and depression, he added. More research is also needed to evaluate methods for training MS clinicians on better identifying these emotional disorders, and how best to educate patients and their families to recognize them and how to encourage more open discussion of these underlying problems,” Dr. Jones said.

LINK UP FOR MORE INFORMATION:

•. Berrigan L, Fisk JD, Patten SB, et al. on behalf of the Canadian Institutes of Health Research Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Health-related quality of life in multiple sclerosis: Direct and indirect effects of comorbidity http://www.neurology.org/content/early/2016/03/09/WNL.0000000000002564.short. Neurology 2016; Epub 2016 March 9.
    •. Minden SL, Feinstein A, Kalb RC, et al. Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology http://www.neurology.org/content/early/2013/12/27/WNL.0000000000000013.full.pdf+html. Neurology 2014; 82:174–181.
    •. Marrie RA, Fisk JD, Tremlett H, et al. on behalf of the Canadian Institutes of Health Research Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Differences in the burden of psychiatric comorbidity in MS vs the general population http://www.neurology.org/content/early/2015/10/30/WNL.0000000000002174.long. Neurology 2015;85:1972–1979.
    •. Motl RW, McAuley E, Snook EM, Gliottoni RC. Physical activity and quality of life in multiple sclerosis: intermediary roles of disability fatigue, mood, pain, self-efficacy and social support http://www.ncbi.nlm.nih.gov/pubmed/19085318. Psychol Health Med 2009;14:111–124.
    •. Tepavcevic DK, Pekmezovic T, Stojsavljevic N, et al. Change in quality of life and predictors of change among patients with multiple sclerosis: a prospective cohort study http://www.ncbi.nlm.nih.gov/pubmed/24081871. Qual Life Res 2014;23:1027–1037.