Placebo-controlled trial of zonisamide for the treatment of alcohol dependence.
BACKGROUND
Zonisamide is an anticonvulsant medication with GABAergic, glutamatergic, and monoaminergic effects. Zonisamide has also been shown to reduce alcohol intake in rodents and in risky drinkers in the context of a laboratory study. This pilot clinical trial evaluated the safety, tolerability, and efficacy of zonisamide for the treatment of alcohol dependence.


METHODS
Forty alcohol-dependent subjects (23 men) were randomly assigned to receive treatment with either placebo or zonisamide in a 12-week double-blind trial. Zonisamide was initiated at a dosage of 100 mg/d, which was increased by 100 mg/d every 2 weeks for 8 weeks to a maximum dosage of 500 mg/d. The medication was continued for 4 weeks at the target dosage and then tapered and discontinued. The primary outcomes were drinks per week, heavy drinking days per week, and abstinent days per week, which were measured using the Timeline Follow-Back method.


RESULTS
There was a significant medication by treatment week interaction effect favoring the zonisamide group for heavy drinking days (HDD; P = 0.012), drinks per week (P = 0.004), and alcohol urge scores (P = 0.006). There was not a significant effect on the number or rate of increase in abstinent days. There were no serious adverse events reported and zonisamide treatment was well tolerated.


CONCLUSIONS
The findings provide preliminary support for the use of zonisamide to treat alcohol dependence. Efforts to replicate and extend these findings are warranted.
Arias
Albert J
AJ
Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030-2103, USA. alarias@uchc.edu
Feinn
Richard
R
Oncken
Cheryl
C
Covault
Jonathan
J
Kranzler
Henry R
HR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D055815:Young Adult; D000078305:Zonisamide
D007555:Isoxazoles; D000078305:Zonisamide
Lancet. 2003 May 17;361(9370):1677-85
12767733
J Clin Psychiatry. 2005 Feb;66(2):195-8
15705004
Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6
12941455
J Clin Psychiatry. 2005 May;66(5):617-24
15889949
J Clin Psychiatry. 2003;64 Suppl 8:5-8
12892535
Am J Drug Alcohol Abuse. 2009;35(5):316-9
19637104
Epilepsy Res. 1999 Apr;34(2-3):187-97
10210034
J Clin Psychopharmacol. 2006 Aug;26(4):385-8
16855456
Alcohol Clin Exp Res. 1995 Jun;19(3):600-6
7573780
JAMA. 2007 Oct 10;298(14):1641-51
17925516
JAMA. 2003 Apr 9;289(14):1820-5
12684361
Arch Gen Psychiatry. 1961 Jun;4:561-71
13688369
Pharmacol Biochem Behav. 2007 May;87(1):65-72
17482246
Neurosci Lett. 2009 Apr 17;454(1):91-6
19429061
J Clin Psychiatry. 2006 Dec;67(12):1897-906
17194267
Prog Neuropsychopharmacol Biol Psychiatry. 1994 Jul;18(4):707-15
7938561
J Affect Disord. 2008 Jan;105(1-3):311-4
17586053
Epilepsy Res. 2005 Dec;67(3):153-62
16289509
Fundam Clin Pharmacol. 2001 Dec;15(6):405-17
11860529
Epilepsy Res. 1995 Nov;22(3):193-205
8991786
Addict Behav. 2006 Sep;31(9):1628-49
16472931
Bipolar Disord. 2004 Oct;6(5):432-4
15383137
J Clin Psychiatry. 2004 Jan;65(1):50-6
14744168