title: Interventions for fatigue in peripheral neuropathy.
abstract: BACKGROUND
  Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy.
  
  
  OBJECTIVE
  To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy.
  
  
  METHODS
  On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies.
  
  
  METHODS
  We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies.
  
  
  METHODS
  Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials.
  
  
  RESULTS
  The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo.
  
  
  CONCLUSIONS
  One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.
authors.affiliation: Health & Social Care Research, Faculty of Life Sciences &Medicine, King’s College London, Room 3.22, Shepherd’s House, Guy’s Campus, London, SE1 1UL, UK. Claire.white@kcl.ac.uk.
authors.forename: Claire M
authors.initials: CM
authors.lastname: White
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: Marcel P J
authors.initials: MP
authors.lastname: Garssen
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Stockley
mesh_terms: D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D002607:Charcot-Marie-Tooth Disease / Q000150:complications*; D002648:Child; D005221:Fatigue / Q000209:etiology / Q000628:therapy*; D020275:Guillain-Barre Syndrome / Q000150:complications*; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000150:complications; D016032:Randomized Controlled Trials as Topic
chemical_list: D000547:Amantadine; D001205:Ascorbic Acid