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Original Investigation
June 9, 2008

Improvement of Physical Health and Quality of Life of Alcohol-Dependent Individuals With Topiramate Treatment: US Multisite Randomized Controlled Trial

Author Affiliations

Author Affiliations: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville (Drs Johnson and Ait-Daoud); Ortho-McNeil Janssen Scientific Affairs LLC, Raritan, New Jersey (Drs Rosenthal, Wiegand, Mao, andMcKay and Mss Capece and Beyers); Institute of Internal Medicine, Catholic University, Rome, Italy (Dr Addolorato); Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston (Dr Anton); Division of Psychiatry, Boston University, Boston, Massachusetts (Dr Ciraulo); Department of Psychiatry, University of Connecticut, Farmington (Dr Kranzler); Department of Addictive Behavior and Addiction Medicine, University of Heidelberg, Mannheim, Germany (Dr Mann); Department of Psychiatry, Yale University, New Haven, Connecticut (Dr O’Malley); and Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island (Dr Swift).

Arch Intern Med. 2008;168(11):1188-1199. doi:10.1001/archinte.168.11.1188

Background  Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating γ-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being.

Methods  In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy.

Results  Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels—effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease. Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo.

Conclusion  Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.

Trial Registration Identifier: NCT00210925