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      Drugs & Diseases > Psychiatry

      Wernicke-Korsakoff Syndrome Medication

      Updated: May 16, 2018
      • Author: Glen L Xiong, MD; Chief Editor: David Bienenfeld, MD  more...
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      Medication

      Medication Summary

      Wernicke-Korsakoff syndrome results from thiamine deficiency. The treatment is replacement of this essential vitamin. Previously, the usual dose was 100 mg/day via oral, intravenous, or intramuscular administration. However, the US and International standard of care appears to be shifting towards high-dose thiamine (500 mg tid) for a brief period (2-3 days), then reassessing the patient for improvement. In cases in which the patient is alert and is demonstrating improvement, parental (intravenous/intramuscular) thiamine should continue as long as the patient continues to improve, usually at 250 mg daily.

      In patients who are comatose, intravenous thiamine should be continued, but no clear recommendations have been determined.

      In patients whose responses plateau, which happens with most patients with Wernicke-Korsakoff syndrome, oral thiamine should be administered at 50-100 mg/day to prevent further neurodestruction if the patient continues to drink or will be vulnerable to thiamine deficiency for any other reason.

      It is worth noting that the above recommendations are based on the British Royal College of Physicians guidelines, themselves based on case studies that reported patients who required high doses to demonstrate improvement. Since these recommendations were adopted in the United Kingdom, several other international reports have described patients who required high-dose parental thiamine before Wernicke Encephalopathy symptoms resolved. This regimen is also increasingly recommended by gastroenterologists in the United States and is being adopted by academic medical centers in the United States, Europe, Australia, and New Zealand. The use of this regimen in Wernicke-Korsakoff syndrome is purely an extrapolation of these recommendations and case reports.

      European guidelines are similar but suggest a dose of 200 mg of preferably intravenous thiamine 3 times a day until symptoms resolve.

      In a systematic review from the Cochrane Database, Day et al only found 2 randomized studies that were of sufficient quality. [27] There was a significant difference in favor of 200 mg/day, as compared with 5 mg/d, when the outcomes were measure after 2 days. The review concluded that evidence is insufficient to support specific treatment recommendations with regard to dose, frequency, and duration of treatment. [36] Nevertheless, the Royal College of Physicians recommends thiamine at 500 mg intravenously 3 times per day for 3 days, followed by 250 mg intravenously or intramuscularly for 5 days or until clinical improvement plateaus. [45] The European Federation of Neurological Societies recommends 200 mg intravenous 3 times daily until symptoms resolve. [58]

      The following case reports highlight the current trend and variability on thiamine usage. In a patient with anorexia nervosa, 600 mg/day was given for 6 months; this did not result in any changes from baseline Mini-Mental Status Exam of 27/30. [8] In a patient with pyloric stenosis, high-dose thiamine treatment (900 mg intramuscular daily with 600 mg orally daily for 5 days, and 900 mg intramuscular daily for 7 more days) resulted in rapid neurological and radiographic improvements, although cognitive impairment was still severe. [59] In a separate case report on a diabetic patient with Wernicke encephalopathy and central pontine myelinosis (and normal serum thiamin levels), 1000 mg/day (of fursultiamine) led to attenuation of neurological deficits on day 7. [60]

      For persistent cognitive impairment (eg, Korsakoff dementia), cognitive enhancers such as acetylcholinesterase inhibitors and memantine have demonstrated some benefit. [61, 62] However, the findings were negative in a small comparison study with rivastigmine. [63]

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      Nutrients

      Class Summary

      In treating Wernicke-Korsakoff syndrome, the objective is to replenish vitamin B-1 stores. In adults, 60-180 mEq of potassium, 10-30 mEq of magnesium, and 10-40 mmol/L of phosphate per day appear necessary to achieve optimum metabolic balance.

      Thiamine

      Thiamine is a water-soluble vitamin that combines with adenosine triphosphate (ATP) to form the coenzyme thiamine pyrophosphate, which is necessary for carbohydrate metabolism. The B vitamins are readily absorbed from the gastrointestinal tract (except in cases of malabsorption syndromes). Alcohol inhibits the absorption of thiamine, which occurs primarily in the duodenum.

      Magnesium sulfate

      Magnesium sulfate is a cofactor in a number of enzyme systems; it also is involved in neurochemical transmission and muscular excitability. Patients with chronic alcoholism and patients who are malnourished usually have inadequate magnesium stores.

      Potassium acid phosphate (K-Phos)

      Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through gastrointestinal loss, or because of low intake. Patients with chronic alcoholism and those who are malnourished usually have inadequate nutrient stores. Potassium depletion sufficient to cause a 1-mEq/L drop in serum potassium requires a loss of about 100-200 mEq of potassium from the total body store.

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