Multiple sclerosis (MS) is a disease of the central nervous system characterized by an immune-mediated attack on the myelin and oligodendrocytes, resulting in inflammatory lesions, astrocytic scarring, and axonal loss. It is estimated that more than 300,000 people in the United States have MS, and there is some epidemiologic evidence that the incidence is increasing in women. Symptoms of MS are wide ranging in nature and severity and may or may not include disturbances in gait, balance, vision, bladder and/or bowel function, sensation, sexual function, psychiatric status, and cognition. The course of MS is highly variable, although the expected life span is decreased only by a few years.
Psychosocial Challenges
MS is an unpredictable, potentially disabling disease. Although outcomes can be estimated in large epidemiologic studies and follow-up studies from large clinical trials, it is very difficult to predict long-term outcomes for a given individual. This uncertainty represents a challenge to the coping capacity of persons with MS. There are a number of specific psychosocial challenges, including clinical depression, anxiety, sexual dysfunction, cognitive changes, and demoralization and grief associated with MS-related losses.
Clinical Depression and Grief
Depression is the most common psychiatric disorder in MS. Major depression is a serious psychiatric disorder that is distinguished from minor depression, discouragement, and grief by the persistence, severity, and number of symptoms.
According to the Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision, a diagnosis of major depression requires an individual to have a sad or irritable mood most of the day and nearly every day for at least 2 weeks. In addition, there must be 4 other symptoms present during this time, which may include:
- anhedonia (loss of interest in the things one is usually interested in and capable of doing);
- feelings of worthlessness or excessive/inappropriate guilt;
- significant increase or decrease in appetite with weight gain or loss;
- change in sleep patterns (waking up 2-3 hours earlier than usual, or increase in number of hours of sleeps each day, by several hours or more);
- recurrent thoughts of death or suicidal feelings and thoughts;
- fatigue;
- attentional impairment; and
- sexual dysfunction.
Some of the symptoms associated with major depression are also associated with MS. Consequently, it's important to differentiate between social withdrawal associated with depression (due to loss of interest in usual social activities) and the inability to socialize in one's usual manner due to MS symptoms or impairments. If the persistent and severe mood changes that characterize major depression are not present, such symptoms are most likely due to MS.
Major depression among those with MS is consistently related to a loss in the perceived quality of life and is associated with decreases in self-care, including adhering to disease-modifying medications in MS, the failure of which may lead to long-term disease morbidity. In contrast to clinical depression, normal grief tends to occur after a loss (eg, recent exacerbation that produced permanent neurologic impairments). Grief is not associated with significant sustained impairments in function and is not typically associated with anhedonia.
In MS there is increased suicidal risk. One study that evaluated death records in MS found that suicide rates in MS patients were up to 7.5 times greater than in the general population. These findings are supported by other studies that show that suicidal ideation and lifetime suicidal intent among individuals with MS were approximately 18% and 28% respectively.
Evidence from several studies suggests that many MS patients who experience major depression are not treated or are significantly undertreated for their depressive symptoms. The latter studies highlight the need for increased systematic screening in MS for depression. Decreases in depression in MS patients receiving treatment for depression have also been associated with decreases in in-vitro antigen-specific and non-antigen-specific TH1-mediated interferon-gamma production, which may reflect an underlying inflammatory component associated with major depression in MS.
Because numerous studies estimate that between 36% and 60% of MS patients will experience an episode of major depression at some point during their lifetime, it is imperative to screen for depression during visits. Recommendations for screening have included the use of self-report scales, such as the Beck Depression Inventory II, Patient Health Questionnaire, and Chicago Multiscale Depression Inventory. One study found that simply asking the following questions was able to detect the presence of a major depressive episode with high sensitivity and specificity:
During the past 2 weeks, have you often been bothered by feeling down, depressed, or hopeless?
During the past 2 weeks, have you often been bothered by little interest or pleasure in doing things?
Several randomized trials in MS have indicated that depression can be treated successfully with a variety of antidepressant medications, cognitive-behavioral therapy, or both. The relative effect sizes of antidepressant therapy and cognitive-behavioral therapy on depression in MS have been found to be similar, so individuals can be offered a choice. However, in patients with severe depression, mental health professionals consider antidepressant therapy the first line of treatment, with psychotherapy serving as an important adjunctive therapy. There is some evidence that offering both antidepressant treatment and psychotherapy will confer improved long-term outcomes over either treatment alone.
Anxiety
The prevalence rates of clinically significant symptoms of anxiety in MS vary from 12% to 90% with most studies indicating 30% to 50%. Risk factors for anxiety disorders in MS patients have included female sex, time since diagnosis, comorbid diagnosis of depression, limited social support, and disability status. MS patients report significantly more anxiety than do healthy controls, with anxiety symptoms associated with fatigue, sleep disturbance, problem-solving deficits, pain, and disability status. It is possible that screening assessments or targeted interventions can be put into place based on the findings about prevalence rates or predictors of anxiety.
The point-prevalence of clinically significant anxiety was found to be 25% in one study, which was 3 times the rate of clinically significant depression in the sample. Females were significantly more anxious than males, and anxiety comorbid with depression was associated with increased thoughts of self-harm, more somatic complaints, and greater social dysfunction.
Social anxiety has also been found to be common. In one study, 30.6% of serial clinic patients met criteria for social phobia (fear and avoidance of social situations) on the Social Phobia Inventory, which was not associated with severity of disability. The presence of social phobia was associated with reduced health-related quality of life. To date, no treatments for social phobia in MS have been reported in the literature.
Injection phobia is also fairly common in MS. This is a problematic symptom, as most disease-modifying therapies are delivered by injection and require a schedule of either subcutaneous or intramuscular injections ranging in frequency from daily to weekly. Patients with injection phobia often select a family member/friend/other to conduct the injection, which is strongly linked to poor long-term adherence.
Cognitive-behavioral therapy for the treatment of injection phobia in MS patients was successful in one small sample pilot study published to date. In this study, 8 patients who could not self-inject due to phobia were able to do so within 7 treatment sessions, and 7 of 8 patients continued to self-inject at 3-month follow up. Given poor long-term adherence associated with non-self-injection, it is advisable to treat injection phobia early.
The MS literature cites the treatment of generalized anxiety with psychopharmacologic agents, including benzodiazepines and SSRI's. To date, one randomized clinical trial of short-term (6 weeks) cognitive-behavioral therapy reported clinically significant reductions in anxiety (and comorbid depression) with treatment (cognitive-behavioral therapy combined with progressive deep-muscle relaxation training adapted for patients with MS) relative to non-treatment (MS clinic services only). This study also reported that treated patients showed increases in coping behaviors that were associated with better emotional management and problem-solving behaviors. More recently, a 1-year, open-label trial of escitalopram in women with relapsing-remitting MS reported reduced risk for relapses associated with stressful life events; results will need to be replicated in larger samples with better controlled studies.
Cognitive Dysfunction in MS
Prevalence studies report that 43% to 65% of persons diagnosed with MS have objective cognitive impairments on neuropsychological tests. The prevalence rates range widely, in part due to sampling and other study design issues. Studies that focused on community samples of MS patients and excluded clinic patients report lower rates, while studies that sampled clinic patients report higher rates.
The types of cognitive impairments identified in MS are wide ranging and have included slowed processing speed, impairments in verbal and visual memory, various aspects of attention, visual-spatial judgment, verbal fluency, and executive function. Cognitive impairments can occur very early in MS, and several studies have identified impairments in patients with clinically isolated syndrome before meeting the criteria for clinically definite MS. The severity of cognitive impairment in MS also ranges widely, mirroring the variability of other clinical symptoms. Most patients have multifocal impairments with relatively good preservation of premorbid language abilities and some aspects of reasoning skills. Occasionally the severity is extreme, with the obvious presence of a dementia. Natural history studies are few but have indicated that patients identified with a focal cognitive impairment are likely to have progression of that impairment longitudinally and to develop additional impairments.
Cognitive impairments have been found to be highly associated with employment problems, social problems, difficulties in activities of daily living, and quality of life. The presence of a cognitive impairment cannot be predicted from the overall severity of disability, as numerous studies report the relationship between them to be quite modest. Cognitive impairments correlate better with a variety of MRI metrics, including T2 lesion load, T1 "black hole" lesions, cerebral atrophy, diffusion tensor imaging, and diffusion-weighted imaging studies. Third-ventricle width has been highly associated with the presence of cognitive impairments, probably due to the relationship between proximal thalamic and other structures that are highly related to cognitive function. Overall, studies have indicated that measures of atrophy account for more variance in cognition than does lesion burden.
The literature on the treatment of cognitive impairments is relatively sparse. Symptomatic treatment studies are inconclusive or largely negative. There are few large-scale, well-controlled, or well-designed studies on cognitive rehabilitation to date, although preliminary studies have found that verbal learning and memory can be improved objectively. Evidence from substudies of clinical trials of disease-modifying therapies indicates that cognitive impairments can be prevented or delayed. Studies of beta-interferon 1a and 1b found fewer cognitive deficits at the end of trials in patients randomly assigned to active treatment arms, although substudy data from a clinical trial of glatiramer acetate did not find differences between groups. Differences in results between disease-modifying therapies must not be overinterpreted, however, because these trials were not designed or powered to evaluate cognitive outcomes as either primary or secondary endpoints. Future studies that are designed and powered for that purpose will shed better light on the impact of disease-modifying therapy on cognition.
This article was originally published in
Medscape by authors: Frederick W. Foley, PhD, faculty and disclosures
