ARTICLE IN BRIEF
The report highlights the evidence-based review of literature on managing psychiatric disorders in multiple sclerosis, and identifies areas where more research is needed.
Although rates of depression, anxiety, and other psychiatric disorders are higher among multiple sclerosis (MS) patients than the general public, there is little quality research data on how best to screen, diagnose, and treat such problems, according to a new evidence-based guideline from the American Academy of Neurology. The guideline was published online on Dec. 27 ahead of the Jan. 14 print edition of Neurology.
Neurology Today asked senior author and AAN Guideline Development Subcommittee member Pushpa Narayanaswami, MD, assistant professor of neurology at Harvard Medical School/Beth Israel Deaconess Medical Center in Boston, to review the panel's findings.
WHAT DO YOU THINK WAS THE MOST IMPORTANT FINDING?
Studies suggest that the incidence of psychiatric disorders, especially depression and anxiety, are higher in MS patients as compared with the general population, and suicide may be twice as common in this population. I think this guideline highlights the lack of strong evidence-based information in the medical literature to determine the best ways to screen and diagnose psychiatric disorders in people with MS, and to decide what pharmacologic and non-pharmacologic treatments are most effective in this population.
DO ANTIDEPRESSANTS OR ANTI-ANXIETY MEDICATIONS WORK DIFFERENTLY IN MS PATIENTS?
That's the problem, we just don't know — there just has not been enough good quality research in the literature. We don't know if they are as effective in treating depression and anxiety in people with MS as they are in the non-MS population. Despite the lack of evidence, these medications are commonly used to treat emotional disorders in people with MS. We need rigorously designed, high quality studies on treatment of psychiatric disorders in people with MS to see what treatments work, how safe they are in people with MS, and how they interact with treatments for MS. That means we need more funding for research into these crucial areas. We have outlined a number of areas in the guideline as recommendations for future research.
WHAT ABOUT RATES FOR OTHER PSYCHIATRIC DISORDERS?
From our review of the literature, the prevalence rate for major depression may be in the range of 36 percent to 54 percent, compared with around 16 percent in the general population. The prevalence of bipolar disease is around 13 percent in MS patients, compared with 1 percent to about 4 percent in the general population, while the prevalence of anxiety disorder is estimated to be nearly 36 percent in people with MS versus nearly 29 percent in other individuals. The prevalence of adjustment disorders in MS is about 22 percent compared with around 2 percent in the general population. In people with MS, pseudobulbar affect (PBA), a disorder characterized by involuntary or uncontrollable episodes of crying and/or laughing, may be present anywhere from 6 percent to 46 percent.
It is also important to note that many MS patients need corticosteroids to reduce the severity of relapses, and these medications have been linked to depression and manic/hypomanic symptoms. However, the effect of corticosteroids on mood in people with MS is unclear. We also do not know the effects of disease-modifying therapies such as interferons on mood.
WHAT SCREENING OR DIAGNOSTIC TOOLS ARE HELPFUL IN MS PATIENTS?
According to the evidence, the CNS Emotional Lability Scale (CNS-LS) may be useful to screen for pseudobulbar affect. The CNS-LS is a 7-item questionnaire that is completed by patients or caregivers. It rates the frequency of episodes of uncontrollable laughing and crying on a 5-point scale; higher scores indicate more frequent episodes. Using a cut-point of 17 on this scale, investigators were able to determine pseudobulbar affect with 94 percent sensitivity, 83 percent specificity, with an 87 percent positive predictive value (PPV), and a 92 percent negative predictive value (NPV).
Three tools may help in screening MS patients for depression: the Beck Depression Inventory (BDI), General Health Questionnaire, and a two-question screen.
A Class II study of the original BDI found that, using a score of 13 as the cut-point, depressive disorders were diagnosed with 71 percent sensitivity and 79 percent specificity, with 70 percent PPV, and 79 percent NPV.
A Class II study evaluating the General Health Questionnaire found that it was quite sensitive and specific (92 percent) to diagnose broadly defined “emotional disturbances.” [The General Health Questionnaire, which assesses general well-being and distress, asks respondents to evaluate their current state and whether that differs from their usual state — looking for an inability to perform normal functions and the appearance of new and distressing phenomena.]
Finally, a two-question screen — where the patient is asked whether he or she has depressed mood and diminished interest or pleasure in activities — was also found to be useful to screen for depression, with a high sensitivity greater than 98 percent but lower specificity (87 percent).
The take-home message from these studies is that clinicians may use the original BDI and a two-question tool to screen for depressive disorders, and the General Health Questionnaire to screen for more broadly defined emotional disturbances, and the CNS-LS to screen for pseudobulbar affect.
The panel concluded that there is insufficient evidence either for or against other screening tools. Some symptoms such as fatigue (somatic/neurovegetative symptoms) may be due to the disease itself, or due to mood disorders such as depression. It is unknown if the presence of these symptoms affects the accuracy of these tools in detecting depression. We also did not find evidence for or against the use of any diagnostic instruments or clinical evaluation procedures for diagnosing psychiatric disorders in MS.
WHAT TYPES OF TREATMENT MAY HELP PATIENTS WITH THESE CONDITIONS?
Again, the problem is that there is little data in the literature about effective therapeutic approaches specifically targeting MS patients. We found evidence that a 16-week telephone-administered individual cognitive behavior therapy program may help to treat depressive symptoms. A combination of dextromethorphan and quinidine for pseudobulbar affect (Nuedexta) was approved about three years ago to treat PBA. Based on the evidence, we recommended that it may be useful to treat PBA in people with MS.
We found insufficient evidence for or against the effectiveness of the antidepressants sertraline, desipramine, or paroxetine for individual in-person, or group CBT. Evidence was also lacking for or against the efficacy of individual or group relaxation training or group CBT for MS patients with anxiety disorders.
Likewise, we found that evidence was lacking to determine the psychiatric effects of disease-modifying and symptomatic therapies and corticosteroids. We have little data on whether or not any of the medications MS patients use for MS might cause or play a factor in the development of depression, anxiety, or other psychiatric disorders. Evidence is also not available to determine the risk factors for suicide in people with MS or for the treatment of psychotic disorders in this population.
Although we know that MS patients are also using many of the medications used to treat depression and anxiety in the general population, we unfortunately do not have the evidence to make any conclusive recommendations. But remember, a lack of evidence does not mean that these approaches are not effective for patients. It just means we do not know.
WHAT DID THE PANEL RECOMMEND IN TERMS OF FUTURE RESEARCH NEEDS?
It is clear that we need more research on the effectiveness of both pharmacologic and non-pharmacologic treatments in MS patients. Despite awareness among clinicians that emotional disorders are common in patients, these disorders may be undetected and/or inadequately treated.
We need more direct comparisons of screening tools and diagnostic instruments to determine which tools best identify particular emotional symptoms and disorders in people with MS. We also need to determine methods that are useful to train MS clinicians to better identify emotional disorders, and methods to educate patients and families to recognize emotional symptoms, and discuss them with their doctors.
Studies evaluating the feasibility, cost, use of results, and outcomes of screening initiatives are also needed. Some somatic and neurovegetative symptoms can be attributed to both an emotional disorder and MS, and at present it is difficult to determine if symptoms such as lack of energy, for instance, are due to the disease itself, or due to depression. Research focusing on tools to determine the source of these symptoms is essential.
With regard to treatment, we need large, methodologically rigorous, randomized, placebo-controlled studies of non-pharmacologic and pharmacologic therapies used in the general population to determine their safety and efficacy in people with MS. We also need a systematic examination of combinations of pharmacologic and non-pharmacologic therapies in these patients, as well as assessments of treatment options for euphoria, apathy, and emotional dysregulation.
It is important to note that we only reviewed studies in adults with MS, so research into these disorders in children and adolescents with MS is also required.
I believe that this report will help raise awareness among clinicians and the general public about psychiatric disorders that can affect individuals with MS. We also hope this guideline will help raise awareness of these gaps in the research literature and stimulate funding for more studies.