A pilot trial of topiramate for the treatment of cocaine dependence

Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut Street, Philadelphia, PA 19104, USA.
Drug and Alcohol Dependence (Impact Factor: 3.42). 10/2004; 75(3):233-40. DOI: 10.1016/j.drugalcdep.2004.03.008
Source: PubMed


Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.
The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).
Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05).
Topiramate may be effective for the treatment of cocaine dependence.

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    • "A pilot study has also examined whether topiramate can be efficacious in the treatment of cocaine use disorders (Kampman et al., 2004). This medication is believed to reduce cocaine craving and was administered in a 13-week controlled trial to 20 treatment-seeking men and women who all met criteria for cocaine use disorder. "
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    • "Several RCTs have found Modafinil – also in conjunction with CBT – to reduce cocaine use and craving (Anderson et al., 2009; Dackis, Kampman, Lynch, Pettinati, & O'Brien, 2005); a meta-analysis concluded that modafinil was superior to placebo in achieving cocaine abstinence (Castells et al., 2010). Mixed effects on cocaine use and craving have been documented in studies involving Topiramate (also combined with CBT; (Kampman et al., 2004; Nuijten et al., 2011; Reis, Castro, Faria, & Laranjeira, 2008), results for Acamprosate or Memantine have been largely negative (Bisaga et al., 2010; Kampman, 2010). Various GABA agents (e.g., Vigabatrin, Baclofen, Taigabine) have shown no or mixed effects at best (e.g., Brodie et al., 2009; Shoptaw et al., 2003; Winhusen et al., 2007), and both a systematic review/meta-analysis and a Cochrane review, each involving 15 studies, concluded that there was no current evidence supporting the use of anti-convulsants for cocaine dependence treatment (Alvarez, Farré, Fonseca, & Torrens, 2010; Minozzi et al., 2008). "
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    • "Study eligibility criteria were as follows: (a) cocaine and opioid dependence (based on an evaluation with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , fourth edition [DSM–IV] [SCID]) and seeking treatment; (b) age between 18 and 55 years; (c) eligible to receive methadone maintenance treatment; (d) no allergy to sulfonamide medications or topiramate; (e) no chronic disorders with risk of acidosis; (f) no history of nephrolithiases or unexplained hematuria; (g) not on Highly Active Antiretroviral Therapy; (h) no glaucoma, family history of glaucoma, intraocular pressure Ͼ20 mm Hg, or onesided blindness (i) no seizure disorder or use of antiepileptic medications; (j) no current benzodiazepine dependence; (k) no serious psychiatric illness (psychosis, dementia); and (l) no pregnancy , lactation, or refusal to use an effective contraceptive method. Computerized randomization to placebo and topiramate groups was stratified on (a) gender, (b) age (Յ40 years old, Y/N), (c) cocaine withdrawal severity (Cocaine Selective Severity Assessment [CSSA] Յ20, Y/N; Kampman et al., 2004), and (d) current alcohol dependence. A detailed description of participant screening and randomization can be found in Umbricht et al. (2014). "
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