Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse

 

Abstract

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 there is uncertainty about appropriate dosage and duration. Current practice guidelines are based on case reports and clinical experience.

Objectives

To determine the quality of evidence for the efficacy of thiamine in preventing and treating the manifestations of WKS as a consequence of alcohol excess, and if so in which form it should be given, at what dose and for how long.

Search strategy

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 22 January 2008 using the terms: thiamin* OR aneurin*. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.

The search in August 2005 retrieved no new studies for inclusion; the latest search of January 2008 retrieved one possible study for inclusion, which was excluded.

Selection criteria

All randomized trials in which treatment with thiamine or thiamine-containing products was administered and compared with alternative interventions for people with, or at risk of developing, WKS secondary to alcohol abuse.

Data collection and analysis

All abstracts were independently inspected by two reviewers (ED & PB) and relevant papers were retrieved and assessed for methodological quality using Cochrane Reviewers' Handbook criteria.

Main results

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

Authors' conclusions

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

 

Plain language summary

Insufficient evidence of efficacy of thiamine for the treatment of Wernicke-Korsakoff syndrome

Alcohol abuse is an important but not an exclusive cause of Wernicke-Korsakoff syndrome. Although WKS is reasonably well defined and known to cause significant mortality and morbidity, the optimal treatment strategy is not clear. The role of thiamine in treating some of the features of the WKS has been frequently recorded, but recommendations about dosage and duration of treatment are acknowledged to be arbitrary. Two studies were identified that met the inclusion criteria, but only one contained sufficient data for quantitative analysis. This study had methodological shortcomings in design and the presentation of results that limited further analysis. There is therefore insufficient evidence from randomized controlled clinical trials to guide clinicians in the dose, frequency, route or duration of thiamine treatment for prophylaxis against or treatment of WKS due to alcohol abuse.