Treatment of alcohol dependent patients at-risk for subclinical Wernicke-Korsakoff syndrome

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Wernicke-Korsakoff syndrome (WKS) is a neurological disorder caused by thiamine deficiency associated with alcohol dependence or other causes of malnutrition. Although WKS is a common condition, there are currently no universally accepted, national or international, evidence-based guidelines for thiamine dosing for the treatment of either acute symptomatic WKS or for prevention of subclinical WKS-related brain damage in at-risk people. WKS is most commonly seen in alcohol dependent people who therefore constitute a major at-risk population. In the absence of agreed treatment guidelines, different clinical groups or hospital settings tend to maintain their own protocols based on experience or tradition, and in general the dosage levels of thiamine prescribed in Australia for symptomatic WKS varies from lower doses (100-300mg daily) to higher doses (1000mg daily). Australian Department of Health and Aging treatment guidelines recommend 300mg per day for at risk patients (DoHA, 2009). The main aim of this study is to evaluate whether high dose (1000mg daily) thiamine is more effective than Australian standard dose (300mg daily) thiamine for treating subclinical WKS-related brain damage in at-risk alcohol dependent patients admitted for management of their alcohol dependence. The study has direct implications for how this common condition should be treated in the future. In this study, patients will not have acute symptomatic WKS, rather, they will be alcohol dependent patients at risk of subclinical WKS-related brain damage. Patients will be treated as per usual hospital protocols, except that they will be randomly allocated to one of two treatment groups that differ only on dosage amount of thiamine (300mg or 1000mg per day for 3 days) administered via intravenous (IV) infusion. All patients admitted to Depaul House and receiving “treatment as usual” for alcohol withdrawal would routinely have received at least 3 days of thiamine (200mg x two times per day administered intramuscularly) as part of that treatment. Baseline measures, to be obtained before treatment on day 1 and outcome measures obtained after treatment on day 3, include structured examinations of mental health and neurological symptoms, particularly signs associated with WKS such as lack of coordination and irregularity of muscle movement (ataxia) and abnormal eye movements (nystagmus, ophthalmoplegia). Cognitive function will be assessed via standardised tests of working memory and anterograde memory. All participants will receive full hospital care during and after data collection, as per usual hospital protocols for such patients. It was hypothesised that higher doses of parenteral thiamine (1000 mg daily) will lead to greater improvements in specific aspects of cognition and neurological function than lower doses (300mg) in alcohol dependent patients undergoing alcohol withdrawal who are at risk for subclinical WKS-related brain damage.

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