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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    • "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). Prior studies have failed to consistently produce compelling evidence to support topiramate alone as a treatment for any of these disorders (seeShinn and Greenfield, 2010). "
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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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