Why is this so important?
In persons with an alcohol use disorder, thiamine deficiency can lead to a potentially very serious problem–Wernicke-Korsakoff syndrome, which is characterized by abrupt onset of cognitive impairment, an unsteady gait, and ophthalmoplegia although this classic triad is found in only a minority of patients.
Note: The syndrome is more common than we think. Only 20% of cases of Wernicke-Korsakoff syndrome are diagnosed while the patient is alive and the other 80% of cases go undiagnosed (Isenberg-Grzeda et al., 2012).
To prevent Wernicke-Korsakoff syndrome, it is extremely important that thiamine should be given preventively to all persons with an alcohol use disorder even if they don’t show any signs of the syndrome.
The American Psychiatric Association’s Practice Guideline for Treatment of Patients With Substance Use Disorders, Second Edition (2006) recommended giving thiamine “routinely to all patients receiving treatment for a moderate to severe alcohol use disorder.” Similarly, the American Society of Addiction Medicine’s practice guideline (Mayo-Smith, 1997) also recommended that thiamine should be given to all patients with alcohol dependence.
Note: The dose and recommended route of administration of thiamine for the prevention of Wernicke-Korsakoff syndrome are different from
How are we doing?
“Prescribing thiamine to inpatients with alcohol use disorders: how well are we doing?” That’s the title of a study done at a large, inner-city teaching hospital in the US who were referred to the addiction psychiatry service (Isenberg-Grzeda et al., 2014). The short answer is: not that great.
Of these patients, 18% of inpatients with alcohol use disorder had not been prescribed thiamine at all
Another issue is that how thiamine is prescribed should probably depend on whether the patient is at higher risk for the development of Wernicke-Korsakoff syndrome (e.g., with alcohol intoxication, alcohol withdrawal, delirium tremens). Perhaps patients at higher risk should be given a higher dose of thiamine than that for others? And, perhaps the thiamine should be given parenterally in these higher-risk patients than in others? But, in the study described above, similar doses and oral administration were used in both low- and high-risk patients, which is a problem (Isenberg-Grzeda et al., 2014).
Another study (Guirguis et al., 2017) at another teaching hospital in a different part of the US reported similar practices. None of the 2% of patients who had clinical signs suggestive of Wernicke’s encephalopathy or the 7% of patients who were at high risk of developing it received adequate doses of parenteral thiamine. The majority of patients, including those at high risk of developing Wernicke-Korsakoff s
What is not clear
Three critical questions need to be answered: what is the optimal dose of thiamine for the prevention of Wernicke-Korsakoff syndrome, by what route should it be given, and how many times a day?
Unfortunately, neither the APA Practice Guideline (2006) nor the American Society of Addiction Medicine’s guideline (Mayo-Smith, 1997) made any recommendations about how much thiamine to give, for how long, and by what route for the prevention of Wernicke-Korsakoff syndrome in persons with alcohol use disorder.
Note: The APA guideline did make a recommendation that for the treatment of Wernicke-Korsakoff syndrome, we should give 50 to 100 mg of thiamine per day intramuscularly or intravenously. But, here, we are talking about for prevention.
Below, we’ll answer these three questions regarding the preventive use of thiamine in persons with alcohol use disorder: How much? By what route? How many times a day?
A dose of 100 mg per day of thiamine given by mouth has traditionally been recommended in the US. Do you know how it was decided that this was an appropriate dose? Simply based on someone’s estimate of what they would consider to be a high dose compared to the recommended daily intake of thiamine (described in Donnino et al., 2009).
As of February 2019, only one clinical trial has compared different doses of thiamine (Ambrose et al., 2001). The findings from that study were not clear cut but there was a suggestion that the 200 mg per day dose was more effective than lower doses.
The most commonly prescribed dose of thiamine for alcohol use disorder in the USA continues to be 100 mg per day (Isenberg-Grzeda et al., 2014; Guirguis et al., 2017). It is likely that this is inadequate but, for reasons discussed below, giving a higher dose by mouth will not be helpful.
By what route?
Only a small proportion of the thiamine taken by mouth can be absorbed into the body at any given time so that even if 100 mg is given orally, the proportion that is absorbed will be small; it may be that only about 5 mg will get absorbed (Thomson, 2000). And, in persons with an alcohol use disorder, this proportion is likely to be even smaller. Because of this, there is no point in giving a high dose of thiamine orally. If thiamine is given orally, it would be better to give it three times a day.
This problem of low absorption can, of course, be bypassed by giving thiamine parenterally, either intramuscularly or intravenously. The intravenous route is preferred (Galvin et al., 2010).
How many times per day?
The half-life of thiamine given intravenously is about 90 minutes (Sechi, 2008). So, it is recommended that intravenous thiamine be several times per day and this has been recommended by European guidelines (Galvin et al., 2010). By keeping serum thiamine levels high, we can promote continual transfer of thiamine from the blood into the brain.
In deciding what we should do as of February 2019, let’s keep in mind the following five facts:
1. If we don’t give thiamine or enough thiamine to a person who really needed it, the consequences (e.g., Wernicke-Korsakoff syndrome) could be very serious.
2. Concerns about poor absorption of thiamine when taken orally suggest that giving thiamine parenterally may be more reliable.
3. It is not clear what the correct dose of thiamine for prevention is.
4. Thiamine is inexpensive.
5. Thiamine is unlikely to lead to any significant side effects.
To summarize: The risks of undertreating are serious and the risks of overtreating are low (Isenberg-Grzeda et al., 2014).
Based on these facts, what should we do clinically with regard to prescribing thiamine to reduce the risk of Wernicke-Korsakoff syndrome?
The current practice in the US of giving 100 mg once a day of thiamine by mouth is probably not adequate for most patients (Isenberg-Grzeda et al., 2014).
Option no. 1 (Low-risk patients): If we know for a fact that the patient has an adequate diet and the patient has no neuropsychiatric symptoms or signs of Wernicke-Korsakoff syndrome or of peripheral neuropathy, then thiamine may be given orally but 100 mg three times a day (Thomson et al, 2000), at least for the first few days. But, this requires a careful evaluation of the patient to make sure that factors that suggest a higher risk for the development of Wernicke-Korsakoff syndrome are not present?
Option no. 2 (Higher-risk patients): Patients with a history of very heavy alcohol use and/or current alcohol intoxication, those in alcohol withdrawal or delirium tremens, and those with signs suggestive of Wernicke-Korsakoff syndrome may be considered to be at higher risk of developing Wernicke-Korsakoff syndrome. In these patients, the cautious thing to do would be to:
– Give a high dose: 200 mg three times a day (Isenberg-Grzeda et al., 2014), at least for the first few days.
– If at all possible, give the thiamine parenterally, either intramuscularly or intravenously, at least for the first three to five days.
If the thiamine is given intravenously, which is the preferred route and convenient in an inpatient in whom we have intravenous access, the infusion should be given over no less than 30 minutes (Thomson, 2000).
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Chinmay Kulkarni says
How effective is benfotiamine compared with the actual thiamine? Is it absorbed more if compared with thiamine? What is a recommended route and dose of its administration? Thank you