The co-occurrence of alcohol and cocaine dependence is very common. Patients with both cocaine and alcohol dependence tend to have more psychosocial problems and worse treatment outcomes compared to patients addicted to cocaine or alcohol alone. The combined use of alcohol and cocaine is fostered by a variety of factors including conditioning and pharmacodynamic interactions between cocaine and alcohol. Effective pharmacological treatments for combined alcohol and cocaine dependence should include treatments effective for both addictions. Topiramate may be such a treatment. GABAergic neurons function as modulators of the mesocorticolimbic dopamine system and play an important role in regulating the reinforcing effects of both cocaine and alcohol. Increased GABAergic activity may reduce the rewarding properties of both cocaine and alcohol as well as reduce cocaine and alcohol craving. Topiramate, a novel antiepileptic drug with significant GABAergic activity, could therefore be useful in the treatment of alcohol and cocaine dependent patients. Topiramate elevates brain GABA levels and facilitates GABAergic neurotransmission. In two separate pilot trials, topiramate reduced alcohol and cocaine use in alcohol and cocaine dependent patients. At the University of Pennsylvania, topiramate reduced cocaine use in cocaine dependent patients. In a separate trial conducted at the University of Texas, topiramate reduced alcohol use in alcohol dependent patients. The proposed 5-year project will further evaluate topiramate for the treatment of combined alcohol and cocaine dependence in a double-blind, placebo-controlled, 14-week trial. The study will compare topiramate 300 mg daily to placebo in 200 DSM-IV alcohol and cocaine dependent, treatment seeking subjects. Study medications will be given in conjunction with twice weekly individual cognitive behavioral relapse prevention psychotherapy augmented with medical management to improve medication adherence. The primary hypotheses are: 1. Topiramate-treated subjects will have more abstinent days from alcohol and fewer heavy drinking days, as measured by the timeline follow back, compared to placebo treated subjects and 2. Topiramate-treated subjects will use less cocaine during the trial demonstrated by a greater number of days of cocaine abstinence determined by self-report on the timeline follow back and verified by thrice weekly quantitative urinary benzoylecgonine levels.
| Kampman, Kyle M; Pettinati, Helen M; Lynch, Kevin G et al. (2013) A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend 133:94-9 |
| Suh, Jesse J; Pettinati, Helen M; Kampman, Kyle M et al. (2006) The status of disulfiram: a half of a century later. J Clin Psychopharmacol 26:290-302 |
