Is multiple sclerosis patient depressed, stressed, or both?

⁶ reported that extensive hyper intense lesion volume in the left medial inferior prefrontal region with atrophy affecting the dominant anterior temporal lobe was associated with major depression. However, a depression diagnosis in MS patients remains a clinical one that does not require brain imaging studies.

Lack of interest or enjoyment as a symptom of depression can be difficult to identify because MS can diminish enjoyment of some activities. Although patients with MS may need to change their activity patterns to accommodate their illness, the lack of enjoyment in all—or almost all—activities remains a valid indicator of depressive disorder.

MS treatment includes the use of disease-modifying medications such as interferon beta-1b and interferon beta-1a. Several years ago researchers were concerned that interferon beta might cause depression in MS patients based on reports of a suicide and attempted suicide during an early trial of interferon beta-1b in relapsing-remitting MS.⁷ Subsequent studies did not substantiate this concern, however (Box 1).^8,9

Overlapping symptoms such as fatigue and cognitive deterioration could complicate the diagnosis. Look for changing patterns of these symptoms and other signs of depression. Rating scales that do not emphasize fatigue and cognitive impairment—such as the Beck Depression Inventory¹⁰ and the Center for Epidemiologic Studies Depression Rating Scale¹¹—can help identify depression in MS patients.

Fatigue is one of MS’ most common and troublesome symptoms.^12,13 It typically mounts gradually during the day and after activity or heat exposure. Thus, fatigue early in the morning or manifesting as diminished motivation may point to a depressive disorder.

Cognitive deterioration. Clinically significant cognitive dysfunction occurs in 45% to 65% of MS patients.¹⁴ The disease can cause losses in short-term memory, attention, information processing, problem solving, multitasking, and language function.

Bedside cognitive function tests such as the Mini-Mental State Examination¹⁵ often are not sensitive enough to detect MS-related cognitive dysfunction. Be alert for changes in cognitive style when assessing for depressive disorders in these patients. Feelings of worthlessness and guilt or suicidal ideation are not normal MS symptoms and point to depression.

MS patients may experience pathological laughing and crying—also known as involuntary emotional expression disorder (IEED)—a neurologic phenomenon that causes uncontrollable laughing, crying, or anger in the absence of subjective emotional distress. IEED has been reported in approximately 10% of patients with MS (Box 2).^16-22

CASE CONTINUED: Learning to adjust

Since discontinuing paroxetine 5 years ago, Mrs. S has not experienced another depressive episode. However, she describes a history of mood changes associated with pressured speech, increased activity, irritability, and insomnia during cortisone treatment for idiopathic thrombocytopenic purpura 4 years earlier. These episodes were mild, and she did not seek psychiatric treatment.

Mrs. S’ mood episode does not seem to be a recurrence of major depressive disorder because she lacks persistent depressed mood and major depressive symptoms. Her diagnosis is best understood as an adjustment disorder to the progression of her illness and her daughter leaving home. Fatigue is her most debilitating MS symptom.

Medication options

Use a cautious approach to pharmacotherapy. MS patients may have diminished cognitive reserves and might be at increased risk of medication-related delirium.

Depression. Two randomized, controlled trials have confirmed antidepressants’ efficacy for treating depression in MS patients. The studies investigated the tricyclic antidepressant desipramine²³ and the selective serotonin reuptake inhibitor (SSRI) sertraline.²⁴

In a double-blind clinical trial, 28 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy or placebo and psychotherapy. Patients receiving desipramine showed significantly greater improvement than the placebo group, as measured by clinical judgment.

A 16-week study compared the efficacy of cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG), and sertraline in 63 MS patients with major depressive disorder. Results showed that CBT and sertraline were more effective in reducing depression than SEG.²⁴

SSRIs are a common first choice because of their ease of use and general tolerability among MS patients.²⁵ Recommended dosages include:

• citalopram, 20 to 40 mg/d
• fluoxetine, 20 to 40 mg/d
• fluvoxamine, 50 to 300 mg/d
• paroxetine, 20 to 50 mg/d
• sertraline, 50 to 200 mg/d.

There is no consensus that any one antidepressant is best for all MS patients, however. When selecting an antidepressant, consider side-effect profiles, potential for drug-drug interactions, and a history of response to a particular antidepressant. Highly sedating antidepressants such as mirtazapine could aggravate fatigue. Highly anticholinergic agents such as amitriptyline may impair cognitive function.