Effects of Topiramate on Urge to Drink and the Subjective Effects of Alcohol: A Preliminary Laboratory Study

Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02912, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 04/2008; 32(3):489-97. DOI: 10.1111/j.1530-0277.2007.00592.x
Source: PubMed


Topiramate was recently reported to be efficacious in reducing drinking rates and craving among individuals with alcohol dependence in a randomized controlled trial, but dose effects could not be determined. This laboratory study systematically examined the dose-dependent effects of topiramate on cue-elicited craving and other putative mechanisms of its pharmacotherapeutic effects on drinking.
Male and female heavy drinkers (n = 61) were randomized to 1 of 3 medication conditions (200 mg/d; 300 mg/d; placebo) in a double-blind study. Participants reached the target dose after a 32-day titration period, then were stabilized for approximately 1 week. All then participated in a laboratory assessment of alcohol cue reactivity and of the subjective effects of a moderate dose of alcohol.
Both doses of topiramate reduced the frequency of heavy drinking during the titration period as compared to placebo. However, topiramate did not affect self-reported craving for alcohol during the titration period, during the cue reactivity protocol, or in response to the alcohol challenge procedure. Topiramate reduced the stimulating effects of alcohol ingestion compared to placebo, but only in the 200 mg group.
The results of this study support previous findings that topiramate reduces drinking, but the behavioral mechanism underlying this effect does not appear to be attenuation of craving for alcohol as measured using the approaches employed in this study. Rather, the results tentatively suggest that topiramate may exert its beneficial effects by altering the subjective experiences of alcohol consumption. Limitations of the current study are discussed and complementary methods are recommended for future studies, such as the use of behavioral economic paradigms and ecological momentary assessment.

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    • "Topiramate is thought to decrease the acute reinforcing effects of alcohol primarily via antagonizing excitatory glutamatergic projections to the corticolimbic dopamine circuit (i.e., blocking l-alpha-amino-3-hydroxy-5- methyl-isoxazole-4-propionic acid ionotropic[AMPA]/kai- nate[KA]receptors), as well as by facilitating inhibitory GABA transmission (Holmes et al., 2013;Johnson et al., 2007b;White et al., 2000). Topiramate has been shown to reduce craving, withdrawal, and alcohol consumption in alcohol-dependent individuals (Baltieri et al., 2008;Batki et al., 2014;Fl orez et al., 2008;Johnson et al., 2004Johnson et al., , 2007bKomanduri, 2003;Krupitsky et al., 2007;Martinotti et al., 2014;Miranda et al., 2008;Paparrigopoulos et al., 2011;Rubio et al., 2004;Rustembegovic et al., 2001) and is arguably the medication that currently has the most potential as a frontline treatment for AUD (Blodgett et al., 2014;Kranzler et al., 2014). Given that the secondary effects of topiramate's actions on GABA and glutamate transmission may involve reduction of mesolimbic dopamine release (Shinn and Greenfield, 2010), topiramate has been examined in the context of nicotine (Anthenelli et al., 2008;Johnson et al., 2005;Khazaal et al., 2006;Oncken et al., 2014;Reid et al., 2007;Sofuoglu et al., 2006), cocaine (Kampman et al., 2004Kampman et al., , 2013Nuijten et al., 2014;Reis et al., 2008;Umbricht et al., 2014), and methamphetamine use disorders (Elkashef et al., 2012;Johnson et al., 2007a), as well as opioid detoxification and withdrawal (Zullino et al., 2002Zullino et al., , 2005). "
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