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
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.
Available from: Sophie Yorkwillias
- "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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Existing pharmacological treatments for alcohol use disorder (AUD) and other substance use disorders (SUDs) have demonstrated only modest efficacy. Although the field has recently emphasized testing and developing new compounds to treat SUDs, there are numerous challenges inherent to the development of novel medications, and this is particularly true for SUDs. Thus, research to date has tended toward the “repurposing” approach, in which medications developed to treat other mental or physical conditions are tested as SUD treatments. Often, potential treatments are examined across numerous drugs of abuse. Several repurposed medications have shown promise in treating a specific SUD, but few have shown efficacy across multiple SUDs. Examining similarities and differences between AUD and other SUDs may shed light on these findings and offer directions for future research.Methods
This qualitative review discusses similarities and differences in neural circuitry and molecular mechanism(s) across alcohol and other substances of abuse, and examines studies of pharmacotherapies for AUD and other SUDs.ResultsSubstances of abuse share numerous molecular targets and involve much of the same neural circuitry, yet compounds tested because they putatively target common mechanisms have rarely indicated therapeutic promise for multiple SUDs.Conclusions
The lack of treatment efficacy across SUDs may be partially explained by limitations inherent in studying substance users, who comprise a highly heterogeneous population. Alternatively, medications may fail to show efficacy across multiple SUDs due to the fact that the differences between drug mechanisms are more important than their commonalities in terms of influencing treatment response. We suggest that exploring these differences could support novel treatment development, aid in identifying existing medications that may hold promise as treatments for specific SUDs, and ultimately advance translational research efforts.
- "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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Recent political commentary in the USA has suggested that there is great potential for current criminal justice practices designed for drug-involved offenders to be significantly overhauled in the near future. It is imperative to plan for these changes by assessing how well current programs serve drug-involved criminal justice populations. The paper aims to discuss these issues.
This critical assessment begins with an overview of the most recent research on the prevalence and impact that substance use disorders have within the criminal justice system. Although the evidence demonstrates that relying on incarceration as a crime control method for drug-involved offenders has many shortcomings, there are innovative new programs being adopted across the country. Two of these promising programs are discussed, as well as the potential results that could be realized from integrating medication assisted treatment into appropriate criminal justice programs designed for drug-involved offenders.
Incarceration is a failed practice for attending to the underlying reasons why many drug-involved offenders become involved in criminal activities. There are encouraging new programs emerging in different parts of the USA, but the inclusion of supplemental treatment options could further promote positive outcomes.
The impending expansion of criminal justice programs for drug-involved offenders must consider how innovative new programs can be fused with supplemental treatment options to achieve the best results.
Available from: Peter Blanken
- "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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ABSTRACT: There are an estimated several million crack-cocaine users globally; use is highest in the Americas. Most crack users are socio-economically marginalized (e.g., homeless), and feature elevated risks for morbidity (e.g., blood-borne viruses), mortality and crime/violence involvement, resulting in extensive burdens. No comprehensive reviews of evidence-based prevention and/or treatment interventions specifically for crack use exist. We conducted a comprehensive narrative overview of English-language studies on the efficacy of secondary prevention and treatment interventions for crack (cocaine) abuse/dependence. Literature searches (1990-2014) using pertinent keywords were conducted in main scientific databases. Titles/abstracts were reviewed for relevance, and full studies were included in the review if involving a primary prevention/treatment intervention study comprising a substantive crack user sample. Intervention outcomes considered included drug use, health risks/status (e.g., HIV or sexual risks) and select social outcome indicators. Targeted (e.g., behavioral/community-based) prevention measures show mixed and short-term effects on crack use/HIV risk outcomes. Material (e.g., safer crack use kit distribution) interventions also document modest efficacy in risk reduction; empirical assessments of environmental (e.g., drug consumption facilities) for crack smokers are not available. Diverse psycho-social treatment (including contingency management) interventions for crack abuse/dependence show some positive but also limited/short-term efficacy, yet likely constitute best currently available treatment options. Ancillary treatments show little effects but are understudied. Despite ample studies, pharmaco-therapeutic/immunotherapy treatment agents have not produced convincing evidence; select agents may hold potential combined with personalized approaches and/or psycho-social strategies. No comprehensively effective 'gold-standard' prevention/treatment interventions for crack abuse exist; concerted research towards improved interventions is urgently needed.
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