Thiamine for prevention and treatment of Wernicke-Korsakoff syndrome in people who abuse alcohol

Wernicke-Korsakoff syndrome (WKS) is a disorder of the brain caused by a deficiency of vitamin B1 (thiamine). It is characterised by an acute onset of some or all of an eye movement disorder, lack of voluntary coordination of muscle movement (ataxia) and confusion. Patients may die in the acute phase, and many survivors go on to develop permanent memory impairment. Alcohol abuse is an important cause of WKS, although it is not the only consideration. Heavy drinking may lead to particular problems with uptake of thiamine from the diet.

When recognised, WKS is treated with thiamine, but it is not clear how effective this is, particularly in managing the mental features. Recommendations about dosage and duration of thiamine treatment are acknowledged to be arbitrary. We searched for randomised controlled trials comparing thiamine with placebo or alternative treatments, or comparing different thiamine treatments. Two studies were identified that met the inclusion criteria, but  one reported no data that we could analyse, and analysis of the other study was limited by shortcomings in design and in presentation of the results. Therefore no good evidence could be derived from randomised controlled clinical trials to help physicians choose the right dose, frequency, route or duration of thiamine treatment for preventing or treating WKS due to alcohol abuse.

Authors' conclusions: 

Evidence from randomised controlled clinical trials is insufficient to guide clinicians in determining the dose, frequency, route or duration of thiamine treatment for prophylaxis against or treatment of WKS due to alcohol abuse.

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Background: 

Autopsy studies suggest that Wernicke-Korsakoff syndrome (WKS) is not a rare disorder, particularly in individuals who abuse alcohol. Thiamine has been established as the treatment of choice for over 50 years, but uncertainty remains about appropriate dosage and duration. Current practice guidelines are based on case reports and clinical experience. This is an update of a review first published in 2004 and last updated in 2008.

Objectives: 

• To assess the efficacy of thiamine in preventing and treating the manifestations of WKS due to excess alcohol consumption.
• To determine the optimum form, dose and duration of thiamine treatment for this indication.

Search strategy: 

ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 6 September 2012 using the term thiamine OR aneurine. ALOIS contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trial databases and grey literature sources.

Selection criteria: 

Any randomised trials comparing thiamine with alternative interventions or comparing different thiamine regimens (varying in formulation, dose or duration of administration).

Data collection and analysis: 

All abstracts were independently inspected by two reviewers (ED and PWB), and relevant articles were retrieved and assessed for methodological quality using criteria provided in the Cochrane Handbook for Systematic Reviews of Interventions.

Main results: 

Two studies were identified that met the inclusion criteria, but only one contained sufficient data for quantitative analysis. Ambrose (2001) randomly assigned participants (n = 107) to one of five doses of intramuscular thiamine and measured outcomes after 2 days of treatment. We compared the lowest dose (5 mg/day) with each of the other four doses. A significant difference favoured 200 mg/day compared with the 5-mg/day dose in determining the number of trials needed to meet inclusion criteria on a delayed alternation test (mean difference (MD) -17.90, 95% confidence interval (CI) -35.4 to -0.40, P = 0.04). No significant differences emerged when the other doses were compared with 5 mg/day. The pattern of results did not reflect a simple dose-response relationship. The study had methodological shortcomings in design and in the presentation of results that limited further analysis.

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