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.

Download full-text


Available from: Robert Swift,
  • Source
    • "Such findings on safety and mechanisms are vital to deciding whether to invest resources for efficacy testing for a putative addiction medication . Our team has used human laboratory paradigms to test several medications for addiction, including naltrexone (Ray, Bujarski, Chin, & Miotto, 2012; Ray & Hutchison, 2007), topiramate (Miranda et al., 2008; Ray et al., 2009), quetiapine (Moallem & Ray, 2012; Ray, Chin, Heydari, & Miotto, 2011), and varenicline (Ray et al., 2014, 2013). Given the new opportunities presented by recent discoveries on the role of neuroinflammation in addiction as well as new advancements in the technology of medication development , including the refinement of powerful human laboratory models, the stage is set for the discovery of novel treatments for substance use disorders. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies have implicated neuroinflammatory processes in the pathophysiology of various psychiatric conditions, including addictive disorders. Neuroimmune signaling represents an important and relatively poorly understood biological process in drug addiction. The objective of this review is to update the field on recent developments in neuroimmune therapies for addiction. First, we review studies of neuroinflammation in relation to alcohol and methamphetamine dependence followed by a section on neuroinflammation and accompanying neurocognitive dysfunction in HIV infection and concomitant substance abuse. Second, we provide a review of pharmacotherapies with neuroimmune properties and their potential development for the treatment of addictions. Pharmacotherapies covered in this review include ibudilast, minocycline, doxycycline, topiramate, indomethacin, rolipram, anakinra (IL-1Ra), peroxisome proliferator-activated receptor agonists, naltrexone, and naloxone. Lastly, summary and future directions are provided with recommendations for how to efficiently translate preclinical findings into clinical studies that can ultimately lead to novel and more effective pharmacotherapies for addiction.
    International Review of Neurobiology 09/2014; 118C:381-401. DOI:10.1016/B978-0-12-801284-0.00012-9 · 1.92 Impact Factor
  • Source
    • "In the subsample of European Americans (n = 122), topiramate was effective in reducing heavy drinking days only in rs2832407 C-allele homozygotes . In addition, a previous pharmacogenetic analysis of the human laboratory pilot study mentioned previously (Miranda et al., 2008) showed that rs2832407 was associated with the severity of topiramate-induced side effects (Ray et al., 2009). The RCT by Kranzler et al. (2014) did not find an effect of the SNP on adverse events, suggesting that the kainate receptor does not play a unique role in mediating topiramate-related adverse effects. "

    The International Journal of Neuropsychopharmacology 06/2014; 17(10):1-4. DOI:10.1017/S1461145714000790 · 4.01 Impact Factor
  • Source
    • "Although most investigators agree that craving is inherently a subjective experience best described as a state of desire or wanting, the operational defi nition of craving has been debated over the years (Monti et al., 2004). To that end, the subjective stimulating effects (Miranda et al., 2008) and anticipated reinforcement of alcohol (Bohn et al., 1995; Love et al., 1998) have been posited as important contributors to the development and maintenance of craving (e.g., Baker et al., 1986), with some evidence for common genetic underpinnings between subjective effects and desire for alcohol (Hutchison et al., 2008). Further, both subjective responses to alcohol and the subjective experience of craving have been reliably associated with important alcohol-related outcomes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The abbreviated Desires for Alcohol Questionnaire (DAQ) is a self-report assessment of craving comprising the following subscales: (a) strong desires/intentions to drink, (b) negative reinforcement, and (c) positive reinforcement and ability to control drinking. Although the DAQ is sensitive to changes in alcohol craving precipitated by alcohol administration and/or cue exposure, no studies to date have examined the relationship between DAQ scores and subjective responses to alcohol. This study addresses this gap in the literature by testing the relationship between subjective responses to alcohol during alcohol administration and DAQ scores assessed 1 month later. Method: Individuals with alcohol dependence (n = 32) completed a randomized, single-blinded, intravenous alcohol administration in the laboratory in which subjective responses to the alcohol were measured, followed by a visit to the laboratory 1 month later to complete the DAQ. Results: Analyses revealed robust associations between DAQ scores and alcohol craving during alcohol administration (partial correlations: r = .43-.50, ps < .01), with the exception of the positive reinforcement subscale (r = .20, p = .30). Subjective intoxication and sedation were only associated with the negative reinforcement subscale of the DAQ (r = .38, p < .05 and r = .33, p < .05, respectively). Conclusions: Craving, captured by the DAQ, is reliably and positively associated with alcohol-induced craving. The DAQ is also associated with specific dimensions of subjective responses to alcohol. These results support the clinical utility of the DAQ, particularly in large samples where experimental manipulations may not be feasible.
    Journal of studies on alcohol and drugs 09/2013; 74(5):797-802. DOI:10.15288/jsad.2013.74.797 · 2.76 Impact Factor
Show more