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Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.
J Clin Psychopharmacol. 2009 Aug; 29(4):334-42.JC

Abstract

Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.

Authors+Show Affiliations

Medical University of South Carolina, Charleston, SC, USA. antonr@musc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19593171

Citation

Anton, Raymond F., et al. "Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence: Relationship to Alcohol Withdrawal Symptoms." Journal of Clinical Psychopharmacology, vol. 29, no. 4, 2009, pp. 334-42.
Anton RF, Myrick H, Baros AM, et al. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009;29(4):334-42.
Anton, R. F., Myrick, H., Baros, A. M., Latham, P. K., Randall, P. K., Wright, T. M., Stewart, S. H., Waid, R., & Malcolm, R. (2009). Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. Journal of Clinical Psychopharmacology, 29(4), 334-42. https://doi.org/10.1097/JCP.0b013e3181aba6a4
Anton RF, et al. Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence: Relationship to Alcohol Withdrawal Symptoms. J Clin Psychopharmacol. 2009;29(4):334-42. PubMed PMID: 19593171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. AU - Anton,Raymond F, AU - Myrick,Hugh, AU - Baros,Alicia M, AU - Latham,Patricia K, AU - Randall,Patrick K, AU - Wright,Tara M, AU - Stewart,Scott H, AU - Waid,Randy, AU - Malcolm,Robert, PY - 2009/7/14/entrez PY - 2009/7/14/pubmed PY - 2009/9/18/medline SP - 334 EP - 42 JF - Journal of clinical psychopharmacology JO - J Clin Psychopharmacol VL - 29 IS - 4 N2 - Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials. SN - 1533-712X UR - https://www.unboundmedicine.com/medline/citation/19593171/Efficacy_of_a_combination_of_flumazenil_and_gabapentin_in_the_treatment_of_alcohol_dependence:_relationship_to_alcohol_withdrawal_symptoms_ L2 - https://doi.org/10.1097/JCP.0b013e3181aba6a4 DB - PRIME DP - Unbound Medicine ER -