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Antiglutamatergic Strategies for Ethanol Detoxification: Comparison With Placebo and Diazepam
Author(s) -
Krupitsky Evgeny M.,
Rudenko Anatoly A.,
Burakov Andrey M.,
Slavina Tatyana Y.,
Grinenko Alexander A.,
Pittman Brian,
Gueorguieva Ralitza,
Petrakis Ismene L.,
Zvartau Edwin E.,
Krystal John H.
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00344.x
Subject(s) - acamprosate , diazepam , placebo , topiramate , naltrexone , alcohol dependence , pharmacology , memantine , medicine , alcohol withdrawal syndrome , alcohol use disorder , anesthesia , detoxification (alternative medicine) , psychology , nmda receptor , alcohol , antagonist , psychiatry , receptor , chemistry , epilepsy , biochemistry , alternative medicine , pathology
Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up‐regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N ‐methyl‐ d ‐aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate. Methods: This placebo‐controlled randomized single‐blinded psychopharmacology trial studied male alcohol‐dependent inpatients ( n =127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately. Results: All active medications significantly reduced observer‐rated and self‐rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam. Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.