title: Placebo-controlled trial of zonisamide for the treatment of alcohol dependence.
abstract: 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.
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030-2103, USA. alarias@uchc.edu
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Arias
authors.forename: Richard
authors.initials: R
authors.lastname: Feinn
authors.forename: Cheryl
authors.initials: C
authors.lastname: Oncken
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
mesh_terms: 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
chemical_list: D007555:Isoxazoles; D000078305:Zonisamide
references.citation: Lancet. 2003 May 17;361(9370):1677-85
references.pmid: 12767733
references.citation: J Clin Psychiatry. 2005 Feb;66(2):195-8
references.pmid: 15705004
references.citation: Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6
references.pmid: 12941455
references.citation: J Clin Psychiatry. 2005 May;66(5):617-24
references.pmid: 15889949
references.citation: J Clin Psychiatry. 2003;64 Suppl 8:5-8
references.pmid: 12892535
references.citation: Am J Drug Alcohol Abuse. 2009;35(5):316-9
references.pmid: 19637104
references.citation: Epilepsy Res. 1999 Apr;34(2-3):187-97
references.pmid: 10210034
references.citation: J Clin Psychopharmacol. 2006 Aug;26(4):385-8
references.pmid: 16855456
references.citation: Alcohol Clin Exp Res. 1995 Jun;19(3):600-6
references.pmid: 7573780
references.citation: JAMA. 2007 Oct 10;298(14):1641-51
references.pmid: 17925516
references.citation: JAMA. 2003 Apr 9;289(14):1820-5
references.pmid: 12684361
references.citation: Arch Gen Psychiatry. 1961 Jun;4:561-71
references.pmid: 13688369
references.citation: Pharmacol Biochem Behav. 2007 May;87(1):65-72
references.pmid: 17482246
references.citation: Neurosci Lett. 2009 Apr 17;454(1):91-6
references.pmid: 19429061
references.citation: J Clin Psychiatry. 2006 Dec;67(12):1897-906
references.pmid: 17194267
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1994 Jul;18(4):707-15
references.pmid: 7938561
references.citation: J Affect Disord. 2008 Jan;105(1-3):311-4
references.pmid: 17586053
references.citation: Epilepsy Res. 2005 Dec;67(3):153-62
references.pmid: 16289509
references.citation: Fundam Clin Pharmacol. 2001 Dec;15(6):405-17
references.pmid: 11860529
references.citation: Epilepsy Res. 1995 Nov;22(3):193-205
references.pmid: 8991786
references.citation: Addict Behav. 2006 Sep;31(9):1628-49
references.pmid: 16472931
references.citation: Bipolar Disord. 2004 Oct;6(5):432-4
references.pmid: 15383137
references.citation: J Clin Psychiatry. 2004 Jan;65(1):50-6
references.pmid: 14744168