Topiramate in Opiate Withdrawal-Comparison with Clonidine and with Carbamazepine/Mianserin

Opioids selective for the G protein-coupled mu opioid receptor (MOR) produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone), when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. Unfortunately, these medications have critical limitations including those associated with opioid agonist therapies (e.g., sustained physiological dependence and opioid withdrawal leading to high relapse rates upon discontinuation), non-adherence to daily dosing, and non-renewal of monthly injection with extended-release naltrexone. Furthermore, current medications fail to ameliorate key aspects of addiction such as powerful conditioned associations that trigger relapse (e.g., cues, stress, the drug itself). Thus, there is a need for developing novel treatments that target neural processes corrupted with chronic opioid use. This requires a basic understanding of molecular and cellular mechanisms underlying effects of opioids on synaptic transmission and plasticity within reward-related neural circuits. The focus of this review is to discuss how crosstalk between MOR-associated G protein signaling and glutamatergic neurotransmission leads to immediate and long-term effects on emotional states (e.g., euphoria, depression) and motivated behavior (e.g., drug-seeking, relapse). Our goal is to integrate findings on how opioids modulate synaptic release of glutamate and postsynaptic transmission via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors in the nucleus accumbens and ventral tegmental area with the clinical (neurobehavioral) progression of opioid dependence, as well as to identify gaps in knowledge that can be addressed in future studies.

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“…May also block GluR5-containing AMPARs. Showed some promise as an adjunct during detoxification in a small study (Zullino et al, 2004). …”

Section: Relapsementioning

confidence: 99%

Itâ€™s MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

2014

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“…Zullino et al 70 performed a retrospective study comparing topiramate with clonidine and carbamazepine/mianserin in opioid detoxification, and found that topiramate was the best tolerated and most efficacious of the three. Ten consecutively admitted patients treated with topiramate were compared with 10 consecutively admitted patients treated with clonidine and 10 consecutively admitted patients treated with a carbamazepine/mianserin combination.…”

Section: Resultsmentioning

confidence: 99%

Topiramate in the Treatment of Substance-Related Disorders

Shinn¹,

Greenfield²

2010

J. Clin. Psychiatry

105

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Objective To critically review the literature on topiramate in the treatment of substance related disorders. Data Sources A PubMed search of human studies published in English through January 2009. Study Selection 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, ecstasy, and benzodiazepines. Data Extraction Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. Data Synthesis There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate’s superiority over oral naltrexone in alcohol dependence, while one trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and ecstasy are sparse. Conclusion Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate’s unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance related disorders, heterogeneity both across and within these disorders limits topiramate’s broad applicability in treating substance related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.

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“…Limited Kampman et al, 2004Kampman et al, , 2013Nuijten et al, 2014;Reis et al, 2008;Umbricht et al, 2014) Opioids Limited (Zullino et al, 2002(Zullino et al, , 2005) Gabapentin Unknown Alcohol Promising (e.g., Anton et al, 2009Anton et al, , 2011Brower et al, 2008;Furieri and Nakamura-Palacios, 2007;Mason et al, 2009Mason et al, , 2014Trevisan et al, 2008;see Greutman et al, 2015) Cannabis…”

Section: Methamphetaminementioning

confidence: 99%

“…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, 2004Nuijten 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, 2002(Zullino et al, , 2005. Prior studies have failed to consistently produce compelling evidence to support topiramate alone as a treatment for any of these disorders (see Shinn and Greenfield, 2010).…”

Section: Nonapproved Medications Tested As Treatments For Substance Umentioning

confidence: 99%

Clinical Neuroscience of Addiction: Similarities and Differences Between Alcohol and Other Drugs

Karoly

YorkWilliams

Hutchison

2015

Alcoholism Clin & Exp Res

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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.

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Topiramate in Opiate Withdrawal-Comparison with Clonidine and with Carbamazepine/Mianserin

Cited by 17 publications

References 41 publications

Itâ€™s MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

Itâ€™s MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

Topiramate in the Treatment of Substance-Related Disorders

Clinical Neuroscience of Addiction: Similarities and Differences Between Alcohol and Other Drugs

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