Documentation concerning the use of amantadine in multiple sclerosis is requested./nA 35-year old w

Fråga: Documentation concerning the use of amantadine in multiple sclerosis is requested.

A 35-year old woman with severe multiple sclerosis wishes to use this drug. She presently takes zinc, folic acid, mecobolamine and acetylcystein.

Sammanfattning: Amantadine has been shown to have a moderately beneficial effect on MS-associated fatigue in several randomised, controlled studies. However, the method of measurement varies in the different studies and the placebo effect is usually substantial. One study also indicates that amantadine may reduce the number of disease relapses. No effect of amantadine has been seen on cognitive or neurological functioning.

Svar: The pathogenesis of the demyelinating disease multiple sclerosis (MS) has not yet been established. Drug treatment has, so far, been aimed at alleviating the symptoms.

Amantadine is a synthetic anti-viral agent with specific activity against influenza A. Amantadine also causes the release of dopamine in the central nervous system and has weak cholinergic activity (1). Amantadine has been suggested for the treatment of MS-associated fatigue, which occurs frequently and may be a prominent symptom in as many as 40 per cent of the patients. In Sweden, amantadine has only been approved for the treatment of Parkinsonþs disease and type A influenza.

A literature search revealed four double-blind, randomised, placebo-controlled studies evaluating the effect of a 200 mg daily dose of amantadine on MS-associated fatigue. All four studies conclude that amantadine has a small but significant benefit compared to placebo. One study included 115 patients in a 2 times 3 weeks cross-over design, where fatigue was measured by a 50 mm visual analogue scale (VAS) (2). Another study included 29 patients in a 2 times 4 weeks cross-over design and finally one cross-over study included 10 patients, evaluated during 2 times one week (3, 4). A last study compared the effect of amantadine to that of pemoline and placebo in 119 patients divided into three parallel groups over 8 weeks. Two different fatigue scales were used; fatigue severity scale and MS-specific fatigue scale. Amantadine was found to be slightly better than placebo, whereas pemoline, a CNS stimulant, had no effect on fatigue severity (5). Reported side-effects associated with amantadine were for example sleep disturbances (several patients), anxiety (a few patients) and rash (one patient).

Amantadine was also compared to pemoline and placebo in a 6 week parallel group study of cognitive functioning in 45 MS patients. All three groups improved on tests of attention, verbal memory and motor speed, and there was no significant difference between the groups (6).

The effect of amantadine on neurological deterioration and MS relapses was assessed in a long-term, double-blind and placebo-controlled study including 53 MS patients. Seventeen patients in each group completed at least two years of follow-up. Five patients with active treatment suffered relapses compared to 14 on placebo (p=0,038). Relapses also occurred later in the amantadine group. Four patients on placebo died compared to none on amantadine. However, there was no difference in neurological functioning or disability (according to the Kurtzke scale) between the groups (7). 1 Dollery, Terapeutic drugs, 1991; I: A68-A70 2 The Canadian MS Research Group: A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. Can J Neuro Sci 1987; 14: 273-278 3 Cohen RA, Fischer M: Amantadine treatment of fatigue associated with multiple sclerosis. Arch Neurol 1989; 46: 676-680 4 Rosenberg GA, Appenzeller O: Amantadine, fatigue and multiple sclerosis. Arch Neurol 1988; 45: 1104-1106 5 Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, Halper J, Johnson B, Morgante L, Grimson R: Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline and placebo. Neurology 1995; 45: 1956-1961 6 Geisler MW, Sliwinski M, Coyle PK, Masir DM, Doscher C, Krupp LB: Arch Neurol 1996; 53: 185-188 7 Plaut GS: Effectiveness of amantadine in reducing relapses in multiple sclerosis. J Royal Soc Med 1987; 80: 91-93