Clinical Practice Guideline on Assessment and Management of Psychiatric Disorders in Individuals with Multiple Sclerosis

Thursday, May 29, 2014
Trinity Exhibit Hall
Sarah L Minden, MD , Psychiatry, Brigham and Women's Hospital, Boston, MA
Anthony Feinstein, PhD, MD , Psychiatry, University of Toronto, Toronto, ON, Canada
Rosalind C Kalb, PhD , National Multiple Sclerosis Society, New York, NY
Deborah Miller, PhD , Mellen Cener, Cleveland Clinic, Cleveland, OH
David C Mohr, PhD , Preventive Medicine, Northwestern University, Chicago, IL
Scott B Patten, MD, PhD , Community Health Sciences & Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Christopher Bever Jr., MD, MBA, FAAN , VA Maryland Healthcare System, Baltimore, MD
Randolph B Schiffer, MD , Unknown, Santa Fe, NM
Gary S Gronseth, MD, FAAN , Department of Neurology, University of Kansas Medical Center, Kansas City, KS
Pushpa Narayanaswami, MD , Neurology, Beth Israel Deaconess Medical Center, Boston, MA

Background:  Individuals with MS are at increased risk of emotional disorders. If these disorders are not detected and treated, they can worsen functioning and quality of life, interfere with adherence to treatments for MS, and increase the risk of suicide. Since most MS patients are in regular contact with neurologists and/or primary care physicians, providing guidance on improving detection, diagnosis, and treatment practices should help prevent or reduce these negative outcomes. In November 2006, the American Academy of Neurology (AAN) Guideline Development Subcommittee convened a panel of psychiatrists, psychologists, social workers, neurologists, and guideline development methodologists to develop recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with MS.

Objectives: To disseminate evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals MS and make suggestions for future research. 

Methods: We reviewed the literature  from 1950 to August 2011 and evaluated the evidence according to AAN guideline standards. 


1. Weak evidence shows that certain screening tools may help identify emotional disorders in individuals with MS:  the CNS Emotional Lability Scale for pseudobulbar affect (PBA), the Beck Depression Inventory and a 2-question tool  for depressive disorders and the General Health Questionnaire for broadly-defined emotional disturbances. The evidence is not sufficient to support or refute the usefulness of other screening tools, diagnostic instruments, or clinical procedures, or the impact of somatic/neurovegetative symptoms on the accuracy of screening tools and diagnostic instruments.

2. Weak evidence shows that certain treatments may be effective for emotional disorders in individuals with MS: a 16-week program of individual telephone-administered cognitive behavioral therapy (T-CBT) for treating depressive symptoms; dextromethorphan/quinidine for PBA. 

t Clinicians may consider a telephone-administered cognitive behavioral therapy (CBT) program  for treating depressive symptoms (Level C). Although pharmacologic and  nonpharmacologic therapies are  widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed in this review (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U).  Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments commonly used in the non-MS population. 

2. There is evidence supporting the effectiveness of some pharmacologic therapies for depressed mood and anxiety in people without MS. Many of these therapies have not yet been studied exclusively in the MS population. Despite lack of evidence in individuals with MS, these therapies are commonly used to treat emotional disorders in this population.


5. The guideline is limited to the studies that meet AAN levels of quality for analysis. Much more research is needed in this area. Examples of studies that could provide evidence to improve detection, diagnosis and treatment practices include the following:

For screening and diagnosis, head-to-head comparisons of screening tools and diagnostic instruments to determine which best identify particular emotional symptoms (e.g., depressed mood, anxiety) and emotional disorders (e.g., MDD adjustment disorder); evaluations of  methods to train MS clinicians to identify emotional disorders, educate individuals with MS and family members to recognize emotional symptoms, and encourage open discussion of these problem; comprehensive evaluations of screening initiatives including feasibility, cost, use of results, and outcomes; comparisons of methods to distinguish, in an individual, sources of somatic and neurovegetative symptoms that could be attributed to both an emotional disorder and MS; assessments of instruments to screen for and diagnose euphoria, apathy, and emotional dysregulation; appraisals of standard screening and diagnostic instruments to identify and determine the prevalence of other psychiatric disorders among individuals with MS.

For treatment, large, methodologically rigorous, randomized, placebo-controlled studies to evaluate non-pharmacologic and pharmacologic therapies with strong evidence of efficacy and widespread use for treating emotional disorders in individuals without MS. Examples include: double-blind, comparative-effectiveness trials of  commonly used antidepressants with attention to their impact on outcomes of different types of emotional symptoms and disorders, MS impairments (e.g., physical, cognitive), and  concurrent MS treatments; targeted comparative-effectiveness trials for commonly used types of non-pharmacologic interventions (e.g., CBT, psychotherapy) and different approaches  (e.g., individual vs group, telephone vs in-person); systematic examinations of combinations of pharmacologic and non-pharmacologic therapies (and combinations within modalities). Other treatment studies could inlucd replication of findings of safety and efficacy of DM/Q for PBA in individuals with MS and head-to-head comparisons  with other currently used therapies; assessments of treatment options for euphoria, apathy, and emotional dysregulation; evaluations of health care services for individuals with MS  designed to optimize identification and treatment of mental disorders; appraisals of telemedicine technologies among  individuals with MS who are housebound, have difficulty traveling, or live in remote communities.

6. Areas for which there were no studies of sufficient quality to produce recommendations included those related to the effective treatments for psychotic disorders in individuals with MS; clinical evaluation procedures and screening and diagnostic instruments can be used to accurately distinguish between MS fatigue and depression in individuals with MS; the effects of DMAs on mood and affect in individuals with MS? What are the effects of steroids on mood and affect in individuals with MS? What are the effects of symptomatic treatments on mood and affect in individuals with MS? What are the risk factors for suicidal thinking and behavior among individuals with MS?

We included these questions at the outset because they are clinically relevant: Individuals with MS may have psychotic disorders and require treatment. Clinicians may have difficulty determining whether fatigue, for example, is due to MS or depressed mood and therefore selecting appropriate treatment. Individuals with MS may  experience emotional symptoms while taking DMTs, steroids, and symptomatic agents, and may become suicidal. We reviewed studies on these issues, but none met criteria to support recommendations. Neurologists, individuals with MS, and families would welcome well-designed investigations of the effects of interferons on mood.  They would also benefit from knowing whether particular characteristics of individuals with MS might predict suicide.

  • Cognitive and emotional disorders co-occur and it can be difficult to determine the source of  inattention, distractibility, slowed thought processing, and difficulty concentrating. Further research is needed on screening, diagnosing, and distinguishing these disorders and on effective treatments when they co-occur.
  • We reviewed only studies of adults with MS. Future research should address emotional disorders in children and adolescents with MS including comparisons with adults with MS and children and adolescents without MS.