Using Topiramate or Naltrexone for the Treatment of Alcohol-Dependent Patients Gerardo Flo ´ rez, Paz Garcı ´a-Portilla, Sandra A ´ lvarez, Pilar A. Saiz, Luis Nogueiras, and Julio Bobes Background: To compare topiramate versus naltrexone in the treatment of alcohol dependence. Methods: A 6-month naturalistic, randomized and open-label, trial of topiramate versus naltrexone, with assessments at enrollment and after 3 and 6 months of treatment. The setting was an outpatient alcohol clinic. One hundred and two alcohol-dependent patients who had been drinking heavily during the past month were included. Two randomized groups were created. In one, naltrexone was used as the therapeutic agent and, in the other, topiramate was chosen as the therapeutic agent. Both groups received psychological relapse prevention therapy. Outcome was measured using tools that assessed alcohol intake, cravings, disability, and quality of life; changes in biomarkers of alcohol intake were also used. With all the data, a secondary composite measure was created in order to assess each patient’s global alcohol intake and its consequences. Results: Both groups showed substantial reduction in their drinking. Naltrexone patients had higher nicotine consumption throughout the study. Topiramate was better at reducing alcohol- related cravings throughout the study. Both treatments had a similar mean cost throughout the study. Conclusions: Both topiramate and naltrexone were efficacious in the treatment of alcohol dependence, and the treatment costs were similar. There is a trend for topiramate to be superior to naltrexone on critical measures of drinking; however, the study did not have adequate statisti- cal power to establish this fact. Key Words: Alcohol, Topiramate, Naltrexone, Treatment, Craving. A LCOHOL DEPENDENCE IS a common health prob- lem, with a 6.5% estimated lifetime prevalence in the general population (Kessler et al., 2005). This high prevalence makes alcohol dependence a leading preventable cause of morbidity and mortality, because alcohol causes mental disor- ders, gastrointestinal conditions, skeletal diseases, cancers, reproductive disorders, cardiovascular diseases and prenatal harm in a dose-dependent manner and with no threshold effect (Corrao et al., 1999; White et al., 2002). Several medica- tions – naltrexone, acamprosate, and disulfiram - have been approved for the treatment of alcohol dependence (Vocci et al., 2005). But the efficacy and effectiveness trials of these treatments show modest effect. For example, in a recent nal- trexone meta-analysis, the authors concluded that short-term naltrexone treatment decreased the risk of alcohol relapse by 36%, but no short-term efficacy was found in preventing a return to drinking and naltrexone was found to be unable to prevent the risk of discontinuation of treatment (Srisurapanot and Jarusuraisin, 2005). This insufficient improvement is the reason why new medications for alcohol dependence are tested. The anticonvulsant topiramate, a sulfamate-substi- tuted fructopyranose derivative, is one of those medications. Topiramate enhances GABAergic transmission and inhibits glutamatergic transmission. These changes in neurotransmis- sion seem to decrease dopaminergic activity in mesocortico- limbic brain areas, which are related to alcohol addiction (Johnson, 2005). Topiramate facilitates the inhibitory neuro- transmitter c-aminobutyric acid on a nonbenzodiazepine receptor thus decreasing the extracellular release of dopamine in mesocorticolimbic brain areas (Johnson, 2005). Topiramate may also reduce alcohol craving through an inhibitory effect on glutamate receptors of the a-amino-3-hydroxy-5-methylis- oxazole-4-propionic acid (AMPA) and kainate types. In ani- mal models of alcohol craving and relapse AMPA antagonists reduced cue-induced reinstatement of alcohol- seeking behavior and the alcohol deprivation effect (Angeha- gen et al., 2005; Buck, 1996; De Witte, 1996; Faingold et al., 1998; Gordis, 1998; Koob et al., 1998; Sanchis-Segura et al., 2006; Yoshimoto et al., 1992). In several trials, one of which was a double blind, randomized, placebo-controlled trial, topiramate showed efficacy in reducing cravings and heavy drinking and improving abstinence among alcohol-dependent patients (Arnone, 2005; Bobes et al., 2004; Johnson et al., 2003, 2004a,b, 2007). From the Unidad Asistencial ‘‘As Burgas’’ (GF, SA, LN), Ourense, Spain; and Department of Psychiatry, University of Oviedo (PGP, PAS, JB), CIBERSAM, Oviedo, Spain. Received for publication August 29, 2007; accepted March 5, 2008. Reprint requests: Gerardo Flo ´rez, Centro asistencial ‘‘As Burgas,’’ Curros Enrı´quez, 7, 1º local-B, 32004 Ourense, Spain; Fax: +34988371709; E-mail: gerardof@mundo-r.com Copyright Ó 2008 by the Research Society on Alcoholism. DOI: 10.1111/j.1530-0277.2008.00680.x Alcoholism: Clinical and Experimental Research Vol. 32, No. 7 July 2008 Alcohol Clin Exp Res, Vol 32, No 7, 2008: pp 1251–1259 1251