6.1Fatigue

SRs
Review detailsInterventionPopulationResultsQuality assessment+
Author (year)
Branas (2000)[272]

Objective
To assess the efficacy of interventions for fatigue in MS

Number of included studies
6 RCT's
Amantadine vs placebo (4 RCT (n=236))
Pemoline vs placebo (2 RCT (n= 126)
Patients with definite MS complaining of moderate-to- severe fatigueAmantadine: All 4 studies showed a pattern in favour of amantadine compared with placebo, but as the effect size was small there is considerable uncertainty about the validity and clinical significance of the findings.

Pemoline: There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline.
1: Good
2: Good
3: Good
4: Good
5: Good
RCTs and CCTs
Study DetailsInterventionPopulationResultsQuality assessment*
Author (year)
Bass (1990)[276]

Study design
randomised cross-over
Intervention 1
Pemoline (dose not stated), Daily. Oral.

Control
Placebo, Daily.

Treatment duration:
4 weeks treatment, 2 weeks washout then switched

Duration of follow-up:
10 weeks
Condition
MS only

Number of patients
Total: 31

Age: Not stated.

Duration of MS: Not stated.

Inclusion criteria: Patients with MS with major symptoms of fatigue.
Visual analogue scale (patient self report): + ve
Patients preference of treatment: + ve

Drop outs:
4 all due to exacerbations (2 on pemoline and 2 on placebo)
Adverse effects:
Insomnia was the principal side- effect.

Data extract from abstract only.
1: Yes
2: Not clear
3: Yes
4: Yes
5: Not clear
6: Yes
Author (year)
Geisler (1996)[275]

Study design
RCT
Intervention 1
Pemoline (18.75 mg titrated upward to max dose of 56.25mg), Daily. Oral.
Intervention 2
Amantadine (200 mg), Daily. Oral
Control
Placebo, Daily.

Treatment duration:
6 weeks

Duration of follow-up:
6 weeks
Condition
MS only

Number of patients
Total: 45 (Int 1: 16; int 2: 13; control: 16)
RR: 38
PP: 7

Age: 40.3 years

Duration of MS: Not reported

Inclusion criteria: Patients with clinically or laboratory definite MS (Poser) and severe fatigue; age 18–50; Fatigue Severity Scale (FSS) score of 4 or more; ambulatory; EDSS 6.5 or less. Patients were excluded if they had severe depression, severe dementia, current or recent MS relapse within 2 months of the study, and no recent or current use of fatigue-producing medication.
Verbal memory: no difference
Visual memory: no difference
Attention/visuomotor search: no difference
SDMT written (one of the attention/visuomotor search scales): + ve
All groups showed improvement, amantadine group showed greatest improvement
Motor speed: no difference
Fatigue levels: no difference

Drop outs:
None reported
Adverse effects:
None reported
1: Yes
2: Not clear
3: Yes
4: Yes
5: Not clear
6: Yes
Author (year)
Murray (1985)[273]

Study design
CCT
Intervention 1
Amantadine (200 mg), Daily. Oral.

Control
Placebo, Daily.

Treatment duration:
3 weeks treatment, 1 week washout and then switched.

Duration of follow- up:
7 weeks.
Condition
MS only

Number of patients
Total: 32

Age: Not reported.

Duration of MS: Not reported.

Inclusion criteria: Patients with definite MS (Schumacher) who had fatigue lasting more than 3 months. Patients with clinical depression were excluded.
Overall improvement (patient rated): + ve
Patients selection of drug for continuing therapy: + ve

Drop outs:
None.
Adverse effects:
7 out of 32 cases reported side effects on amantadine including: hallucinations, nausea, gastric irritation, early morning wakening and hyperactivity. 6 out of 32 cases reported side effects on placebo including nausea, drowsiness, malaise and increased spasticity.
1: No
2: No
3: Yes
4: Yes
5: Yes
6: Yes
Author (year)
Sailer (2000)[274]

Study design
randomised cross-over
Intervention 1
Amantadine (200mg), Daily. Oral.

Control
Placebo (200 mg), Daily.

Treatment duration:
7 days treatment, 7 day washout then switched

Duration of follow- up:
21 days
Condition
MS only (Patients divided into two groups according to disease duration).

Number of patients
Total: 24
RR: 10
SP: 14

Age: 39 years

Duration of MS: 6.5 years.

Inclusion criteria: Patients with clinically definite MS (Poser); documented complaints of fatigue in the past three months; EDSS<=6.5. Patients were excluded if they had an acute relapse in the past 30 days; severe paresis of the upper limbs that would interfere with the experimental procedure; visual acuity of <70%; corticosteroids in last 30 days; severe depression.
Reaction time: no difference
Stimulus selection (ERP to stimuli with relevant colour starting at 200ms): + ve
Response selection (lateralised readiness potential): no difference

Drop outs:
None reported
Adverse effects:
None reported
1: Yes
2: Not clear
3: Yes
4: Yes
5: Not clear
6: Yes

From: Appendix I, Evidence tables

Cover of Multiple Sclerosis
Multiple Sclerosis: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 8.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2004, Royal College of Physicians of London.

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