Is multiple sclerosis patient depressed, stressed, or both?
How to sort through overlapping symptoms and provide appropriate treatment.
Fatigue. Amantadine is the mainstay pharmacologic treatment for fatigue in MS, but evidence for its efficacy is weak.26 Clinical trials of psychostimulants generally have reported disappointing results. One randomized, double-blind trial found no significant differences in fatigue levels between patients receiving pemoline or placebo.27
Some studies have reported reduced MS-related fatigue with modafinil,28-30 but the only double-blind, placebo-controlled trial showed no significant difference between modafinil and placebo in patient fatigue levels.31 In this study, modafinil reduced physical fatigue only in patients with daytime somnolence.
Do interferon beta-1a and 1b—agents used to treat relapsing-remitting MS—cause or aggravate depression?
Two large-scale clinical trials of interferon beta-1a included a validated measure of depressive symptoms—the Center for Epidemiologic Studies Depression Rating Scale.8,9 This scale allowed researchers to conduct a detailed analysis that compared changes in depression symptoms over time in study participants treated with interferon or placebo. Evidence did not indicate increased depressive symptoms in association with interferon treatment.
Conclusion. Depression symptoms that emerge during treatment with one of these agents are not likely caused by the treatment and usually can be managed without discontinuing the drug.
Other psychiatric disorders
Bipolar disorder occurs more frequently in MS patients than in the general population.32 Additionally, some patients with advanced MS might experience benign feelings of euphoria.33 Euphoria can be differentiated from mania by assessing for mania’s other symptoms, such as erratic and disinhibited behavior, rapid speech, increased libido, decreased need for sleep, and excessive energy.
Antidepressants and corticosteroids could aggravate the course of bipolar disorder, and drug-illness interactions with lithium could make side effects such as tremor, diarrhea, and polyuria more difficult to tolerate. Mood stabilizing anticonvulsants such as valproate and carbamazepine are a useful alternative for treating the bipolar patient with comorbid MS. To avoid sedation, start with a low dose and increase gradually.
Approximately 10% of multiple sclerosis (MS) patients develop inappropriate affective expression—anger, laughing, or crying—in the absence of prominent mood changes.16 Involuntary emotional expression disorder (IEED)—or pathologic laughing or crying—is a form of pseudobulbar affect. IEED occurs when affective motor control becomes disinhibited as a result of brain damage from neurologic disease or injury. Conditions associated with IEED include amyotrophic lateral sclerosis, MS, traumatic brain injury, stroke, and dementia.17
IEED can prompt a psychiatric evaluation because uncontrolled crying can seem like intense depression. Symptoms range in severity and include exaggerated and inappropriate affective responses and perceived lack of control over responses. IEED episodes are paroxysmal, occurring in a brief and stereotyped manner, whereas crying in depression is more sustained, less stereotyped, and relates to the underlying mood.17,18 In addition, patients with depressive disorders often suffer difficulties with sleep and appetite as well as thoughts of guilt, hopelessness, and worthlessness not present in IEED.17,19
Studies have shown successful treatment of IEED with antidepressants including tricyclic antidepressants and serotonin reuptake inhibitors.20 A recent randomized, controlled trial suggested that dextromethorphan and quinidine may be beneficial in treating potentially disabling pseudobulbar affect in MS.21 Rating scales such as the 7-item Center for Neurologic Study Lability Scale may help establish a baseline against which to monitor treatment response.22
Insomnia. Sedative hypnotics such as zopiclone can be used for short-term treatment of sleep disturbances. Carefully consider hypnotics’ possible negative effects on balance, coordination, and memory, however.
Psychotic disturbances are rare in MS but occur more frequently in MS patients than in the general population.34 Use low doses of antipsychotics such as olanzapine, quetiapine, or risperidone in MS patients with psychosis. These atypical agents are associated with a lower risk of parkinsonian side effects than typical antipsychotics.
CASE CONTINUED: Coping mechanisms
Mrs. S has difficulty coping with her increasing symptom burden and functional limitations, but she says it is hard for her to ask for help. Her treatment plan includes recruiting support to help her deal with feelings of loss over her daughter’s move. We encourage her to reconnect with friends and family and use community supports for MS patients.
We discuss her treatment options, including biological treatments for fatigue, CBT, and behavioral activation therapy for her mood symptoms. She chooses a course of modafinil, 50 mg/d, and weekly CBT incorporating behavioral activation therapy to increase her activity level and target depressive symptoms and fatigue.
