Nov 7, 2014
Negative results in the treatment of alcoholism
In this sense, we must ask if the standard pharmacotherapy of using benzodiazepines is the best option for alcohol detoxification. Benzodiazepines are related to abusive uses and increasing alcohol cravings, which is directly related to relapse. Other typical drugs and therapies used in alcohol addiction treatment are naltrexone, acamprosate, medical management and combined behavioral intervention (CBI) but just a few studies had been carried out in order to determine the effectiveness or negative results of these therapies separately or combined. An example is the study published by Raymond and col. in 2006 (JAMA, 2006, 295(17) 2003-2017) evaluating the efficacy of the combination of these therapies compared with the placebo effect. In an extensive study with 1383 individuals and 4 years of duration, the authors concluded that the best results, measured like days of abstinence, were observed in subjects with a combination of medical management and naltrexone, CBI or both. However, no improvements were observed in patients treated with acamprosate. Surprisingly, even placebo pills in combination with medical management showed better results than acamprosate. This is a clear example of why this kind of studies must be carried out.
Another example of if other drugs can present better results for alcohol treatment than conventional drugs is the study published by Krupitsky and col. (Alcohol Clin Exp Res, 2007, 31(4), 604–611). In this work, they study three antiglutamatergic drugs (memantine, topiramate and lamotrigine) since ethanol blocks glutamate receptors, and compared their results with diazepam and the placebo effect. They found that these drugs provide similar effects to diazepam in alcohol detoxification, but do not present diazepam’s side effects. They also remark that these are preliminary results and more extensive studies are necessary to determine whether these drugs are more tolerable than diazepam or whether the same effects will be observed in women.
Finally, studies conducted to determine the level efficacy of the conventional and new experimental pharmacotherapies must be conducted extensive and rigorously. The lack of rigor may lead to the rejection of other possible more efficient drugs. This is the case with disulfiram. In a review, C. Brewer explained that disulfiram has been neglected many times, but the studies carry out with naltrexone and acamprosate present small effect sizes in alcohol treatment and disulfiram present better outcomes in meta-analyses and randomized trials. Disulfiram reproduces the features of the ALDH*2, an inefficient variant of the aldehyde dehydrogenase necessary for alcohol metabolization found in homozygote Japanese individuals. This group of Japanese represents a group of individuals that do not drink alcohol for cultural or ethical reasons. They do not drink alcohol just because they cannot efficiently metabolize the acetaldehyde produced in ethanol absorption; they feel ill even with small amounts of alcohol. The accumulation of acetaldehyde produces flushing, nausea and headache. Disulfiram avoids in a reversible way the metabolization of the acetaldehyde and this effect is clearly interesting for alcohol addiction treatment. In some studies, disulfiram, compared with naltrexone and acamprosante, is shown to be more effective reducing craving levels and increasing significantly the number of individuals relapse-free. In addition, disulfiram has shown success in alcohol and cocaine combined addiction treatment, where naltrexona is useless.
Another great difference between disulfiram vs. naltrexone and acamprosante is that disulfiram is not protected by any patent, therefore, is cheaper and it is produced by generic drugs manufacturers. This can facilitate the rejection of this drug by the pharmaceutical industry and getting funding to carry out studies with disulfiram is more difficult.
In conclusion, with these three examples we can see that more effective and rigorous studies about the effectiveness of the current and experimental or new drugs for alcohol addiction treatment must be carry out in order to protect the most vulnerable population of the negative effects of this addiction.
Written by Dr. David Alcántara for The All Results Journals.