Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 47-year-old woman is evaluated for a 6-month history of severe fatigue in the afternoon that is often disabling. The patient has a 15-year history of multiple sclerosis. She states that her mood is good and that she is not feeling depressed or sad. She describes no problems with her sleep, and her partner reports no unusual movements or apnea spells. In the morning, she feels well rested. Medications are glatiramer acetate, low-dose baclofen, and a daily multivitamin.

Physical and neurologic examination findings, including vital signs, are normal. Results of laboratory studies show a hemoglobin level of 12.9 g/dL (129 g/L), a normal mean corpuscular volume, and a serum thyroid-stimulating hormone level of 1.3 µU/mL (1.3 mU/L).

Which of the following is the most appropriate treatment of her fatigue?

A: Amantadine
B: Iron supplementation
C: Levothyroxine
D: Memantine
E: Substitution of an interferon beta for glatiramer acetate

MKSAP Answer and Critique

The correct answer is A: Amantadine.

This patient should be treated with amantadine. She is experiencing multiple sclerosis (MS)–related fatigue, a common but often overlooked symptom of the disorder. Fatigue is described as exhaustion that is unrelated to physical activity and may be exacerbated by hot weather. Exclusion of anemia, sleep disorders, depression, hypothyroidism, and other medical conditions is required to make a diagnosis of MS-related fatigue. Adequate rest, regular physical exercise, and treatment with stimulant drugs can be helpful. Currently, the most frequently prescribed treatments for this symptom are amantadine and modafinil. Amantadine also has antiviral and antiparkinsonian properties.

Although iron deficiency anemia should be part of the differential diagnosis when a patient with MS has fatigue, this patient does not show any evidence of anemia on laboratory testing.

Hypothyroidism is a reasonable consideration in a patient with MS who has fatigue, but this patient’s serum thyroid-stimulating hormone level is in the normal range, which makes levothyroxine therapy unnecessary.

Memantine has been evaluated and found ineffective for improving MS-related cognitive deficits, which this patient does not have, and has no reported benefit in diminishing symptoms of fatigue in patients with the disorder.

Changing this patient’s medication from glatiramer acetate to one of the interferon beta options is inappropriate because her fatigue is not an adverse effect of the glatiramer acetate. Her fatigue also does not constitute an MS relapse, which might necessitate a therapeutic switch.

Key Point

• Amantadine and modafinil are used as symptomatic treatments of multiple sclerosis–related fatigue.

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