TY - JOUR
T1 - What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke–Korsakoff syndrome?
T2 - Results of a randomized controlled trial
AU - Dingwall, Kylie M.
AU - Delima, Jennifer F.
AU - Binks, Paula
AU - Batey, Robert
AU - Bowden, Stephen C.
N1 - Funding Information:
This project was supported by a project grant from the Australian National Health and Medical Research Council (NHMRC; GNT1057968). The funding source had no input into the design of the study or the preparation of this manuscript and the views expressed in this publication are those of the authors and do not reflect the views of NHMRC.
PY - 2022/6
Y1 - 2022/6
N2 - BackgroundThe primary cause of Wernicke–Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose.MethodsTwo double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but “at-risk” alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up.ResultsNo significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings.ConclusionsThe results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.
AB - BackgroundThe primary cause of Wernicke–Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose.MethodsTwo double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but “at-risk” alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up.ResultsNo significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings.ConclusionsThe results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.
KW - dose
KW - thiamine
KW - treatment trial
KW - Wernicke–Korsakoff syndrome
UR - http://www.scopus.com/inward/record.url?scp=85129727940&partnerID=8YFLogxK
U2 - 10.1111/acer.14843
DO - 10.1111/acer.14843
M3 - Article
C2 - 35428992
AN - SCOPUS:85129727940
VL - 46
SP - 1133
EP - 1147
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
SN - 0145-6008
IS - 6
ER -