E Day1, P Bentham, R Callaghan, T Kuruvilla, S George. 1. Department of Psychiatry, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Mindelsohn Way, Birmingham, UK, B15 2QZ.
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: Trials were identified from the latest updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 3 February 2003 using the terms "(thiamin* or aneurin*) and (Korsakoff* or Wernicke* or alcohol*). The CDCIG Specialized register contains up-to-date records from all major health care databases (Medline, Embase, PsycInfo, Cinahl and others) as well as from many trials databases. 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 200mg/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. REVIEWER'S 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.
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: Trials were identified from the latest updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 3 February 2003 using the terms "(thiamin* or aneurin*) and (Korsakoff* or Wernicke* or alcohol*). The CDCIG Specialized register contains up-to-date records from all major health care databases (Medline, Embase, PsycInfo, Cinahl and others) as well as from many trials databases. 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 200mg/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. REVIEWER'S 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.
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