Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder.
alcohol use disorder
gabapentin
pharmacotherapy
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
08
05
2021
received:
20
09
2020
accepted:
23
05
2021
pubmed:
14
6
2021
medline:
22
1
2022
entrez:
13
6
2021
Statut:
ppublish
Résumé
Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13). Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.
Sections du résumé
BACKGROUND
Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD.
METHODS
Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure.
RESULTS
There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13).
CONCLUSIONS
Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.
Identifiants
pubmed: 34120336
doi: 10.1111/acer.14648
pmc: PMC8462978
mid: NIHMS1711880
doi:
Substances chimiques
Anticonvulsants
0
Gabapentin
6CW7F3G59X
Banques de données
ClinicalTrials.gov
['NCT01141049']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1639-1652Subventions
Organisme : NIDA NIH HHS
ID : K23 DA021209
Pays : United States
Organisme : NIDA NIH HHS
ID : K24 DA022412
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA009236
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA017691
Pays : United States
Informations de copyright
© 2021 by the Research Society on Alcoholism.
Références
Ann Neurol. 1996 Jan;39(1):95-9
pubmed: 8572673
Neurology. 1997 Sep;49(3):739-45
pubmed: 9305334
J Pharmacol Exp Ther. 2001 May;297(2):727-35
pubmed: 11303064
Int J Clin Pharmacol Ther. 2018 May;56(5):231-238
pubmed: 29633699
Biochem J. 1999 Sep 1;342 ( Pt 2):313-20
pubmed: 10455017
Alcohol Clin Exp Res. 2014 Jun;38(6):1481-8
pubmed: 24796492
J Stud Alcohol Drugs. 2019 Sep;80(5):572-577
pubmed: 31603760
Alcohol Clin Exp Res. 2009 Sep;33(9):1582-8
pubmed: 19485969
J Clin Psychiatry. 2004 Aug;65(8):1033-4
pubmed: 15323585
J Clin Psychopharmacol. 2009 Aug;29(4):334-42
pubmed: 19593171
J Pharmacol Sci. 2006;100(5):471-86
pubmed: 16474201
Drugs. 2017 Mar;77(4):403-426
pubmed: 28144823
Curr Opin Pharmacol. 2006 Feb;6(1):108-13
pubmed: 16376147
J Stud Alcohol Suppl. 2005 Jul;(15):157-67; discussion 140
pubmed: 16223067
Lancet. 2013 Nov 9;382(9904):1575-86
pubmed: 23993280
J Clin Psychiatry. 2007 Nov;68(11):1691-700
pubmed: 18052562
Epilepsy Res. 2002 May;49(3):203-10
pubmed: 12076841
Lancet. 2003 May 17;361(9370):1677-85
pubmed: 12767733
Addiction. 2019 Sep;114(9):1547-1555
pubmed: 31077485
JAMA Intern Med. 2014 Jan;174(1):70-7
pubmed: 24190578
Psychiatry Clin Neurosci. 2003 Oct;57(5):542-4
pubmed: 12950711
Am J Addict. 2006 Jan-Feb;15(1):76-84
pubmed: 16449096
Alcohol Clin Exp Res. 2007 Feb;31(2):221-7
pubmed: 17250613
Drug Alcohol Depend. 2006 Jun 9;83(1):25-32
pubmed: 16298087
Mol Pharmacol. 2001 May;59(5):1243-8
pubmed: 11306709
Alcohol Clin Exp Res. 2008 Aug;32(8):1429-38
pubmed: 18540923
Neuropharmacology. 1998;37(1):83-91
pubmed: 9680261
Epilepsia. 1999 Jul;40(7):965-72
pubmed: 10403221
Cell Mol Life Sci. 2003 Apr;60(4):742-50
pubmed: 12785720
Arzneimittelforschung. 1994 Mar;44(3):261-6
pubmed: 8192689
Eur Neuropsychopharmacol. 2018 Jul;28(7):795-806
pubmed: 29934090
J Clin Sleep Med. 2005 Jul 15;1(3):284-7
pubmed: 17566190
J Clin Sleep Med. 2007 Feb 15;3(1):24-32
pubmed: 17557449
Ann Pharmacother. 2015 Aug;49(8):897-906
pubmed: 25969570
J Biol Chem. 1996 Mar 8;271(10):5768-76
pubmed: 8621444
Br J Addict. 1989 Nov;84(11):1353-7
pubmed: 2597811
Alcohol Clin Exp Res. 2019 Mar;43(3):522-530
pubmed: 30620410
Alcohol Clin Exp Res. 2019 Jan;43(1):158-169
pubmed: 30403402
Br J Pharmacol. 2002 Jan;135(1):257-65
pubmed: 11786502
Am J Psychiatry. 2011 Jul;168(7):709-17
pubmed: 21454917
Lancet. 2003 May 17;361(9370):1666-7
pubmed: 12767727
JAMA Intern Med. 2020 May 1;180(5):728-736
pubmed: 32150232
Am J Drug Alcohol Abuse. 2016 May;42(3):333-40
pubmed: 26962719
Psychiatry Res. 2018 Dec;270:34-40
pubmed: 30243130
Eur Neuropsychopharmacol. 2017 Dec;27(12):1185-1215
pubmed: 28988943
JAMA. 2018 Aug 28;320(8):815-824
pubmed: 30167705
Alcohol Clin Exp Res. 2020 Sep;44(9):1807-1815
pubmed: 32628784
JAMA. 2007 Oct 10;298(14):1641-51
pubmed: 17925516
J Neurosci. 2008 May 28;28(22):5762-71
pubmed: 18509038
J Psychiatr Res. 2015 Oct;69:150-7
pubmed: 26343607
Epilepsia. 1998 Feb;39(2):188-93
pubmed: 9577999
Neuropharmacology. 2014 Jun;81:95-100
pubmed: 24495399
J Stud Alcohol Suppl. 2005 Jul;(15):170-8; discussion 168-9
pubmed: 16223068
Am J Psychiatry. 2000 Jan;157(1):151
pubmed: 10618048