Topiramate as Treatment for Alcohol Dependence

Stringer, Sarah; Rueve, Marie E.; Mossman, Douglas

doi:10.1001/jama.299.4.405-c

Cited by 3 publications

(2 citation statements)

References 2 publications

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“…Clinical trials of topiramate, an anticonvulsant with some glutamate antagonist activity, have reported decreases in drinking behaviour in alcohol dependence and improvements in quality of life, but with significant adverse effects on memory and concentration111,112. In preclinical studies, topiramate decreased alcohol consumption and preference113 and decreased stress-induced increases in alcohol consumption and preference in mice114.…”

Section: New Targets For Medications Developmentmentioning

confidence: 99%

Development of pharmacotherapies for drug addiction: a Rosetta Stone approach

Koob

Lloyd²,

Mason

2009

Nat Rev Drug Discov

150

120

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Current pharmacotherapies for addiction represent opportunities for facilitating treatment and are forming a foundation for evaluating new medications. Furthermore, validated animal models of addiction and a surge in understanding of neurocircuitry and neuropharmacological mechanisms involved in the development and maintenance of addiction -such as the neuroadaptive changes that account for the transition to dependence and the vulnerability to relapse -have provided numerous potential therapeutic targets. Here, we emphasize a 'Rosetta Stone approach', whereby existing pharmacotherapies for addiction are used to validate and improve animal and human laboratory models to identify viable new treatment candidates. This approach will promote translational research and provide a heuristic framework for developing efficient and effective pharmacotherapies for addiction.Drug addiction is a chronically relapsing disorder characterized by a compulsion to seek and take a drug, loss of control in limiting intake and emergence of a negative emotional state (for example, dysphoria, anxiety and irritability) when access to the drug is prevented 1 . An important goal of current neurobiological research is to understand the molecular, neuropharmacological and neurocircuitry changes that mediate the transition from occasional, controlled drug use to the loss of behavioural control over drug seeking and drug taking that defines chronic addiction. In this Review, we suggest that a combination of validated animal models for addiction, neurobiological targets derived from such models, and translation to and from the clinical domain provides a heuristic framework for the development of pharmacotherapies for addiction. Moreover, the application of known treatments for addiction to existing animal and human laboratory models can provide an evolving 'Rosetta Stone DATABASES Box 1 Disease concept: addiction as a treatable diseaseAddiction is a brain disease, and is defined as a chronically relapsing disorder of compulsive drug use. Advances in our understanding of the neurobiology of addiction have given substantial support to the disease basis for addiction. Changes in specific neuronal and neurochemical circuits have been identified that correspond to different components of the addiction cycle. Perhaps more importantly, these changes are long lasting and in some cases can be permanent. One goal of medications development for addiction is to reverse or compensate for such pathological effects.The concept of addiction as a disease is also supported by overwhelming evidence that addiction leads to brain pathology from a functional perspective, and this pathology is manifested by reversible, and possibly some irreversible, brain changes. In the United States alone, illicit-drug abuse and addiction costs society US$180.9 billion per year 159 ; in addition, alcoholism costs $180 billion 160 and tobacco addiction costs $167 billion 161 .From the perspective of treatment, relapse rates for addiction with abstinence as a goal are high...

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Section: New Targets For Medications Developmentmentioning

confidence: 99%

Development of pharmacotherapies for drug addiction: a Rosetta Stone approach

Koob

Lloyd²,

Mason

2009

Nat Rev Drug Discov

150

120

View full text Add to dashboard Cite

show abstract

“…Topiramate blocks AMPA/kainate receptors, in addition to allosterically modulating ion channel conductance (Shank et al, 2000). Double-blind, placebo-controlled clinical trials have reported decreases in drinking behavior in AUD and improvements in quality of life but with significant adverse effects on memory and concentration (Stringer et al, 2008; Olmsted and Kockler, 2008). Preclinical studies showed that topiramate decreased stress-induced increases in alcohol consumption and preference in mice (Farook et al, 2009).…”

Section: Neurobiological Mechanisms In Alcohol Use Disorder That Are mentioning

confidence: 99%

Emerging pharmacotherapies for alcohol use disorder

Mason

2017

Neuropharmacology

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The identification of different stages within the alcohol use disorder (AUD) cycle that are linked to neurocircuitry changes in pathophysiology associated with the negative emotional states of abstinence has provided a view of medication development for AUD that emphasizes changes in the brain reward and stress systems. Alcohol use disorder can be defined as a chronic relapsing disorder that involves compulsive alcohol seeking and taking, loss of control over alcohol intake, and emergence of a negative emotional state during abstinence. The focus of early medications development was to block the motivation to seek alcohol in the binge/intoxication stage. More recent work has focused on reversing the motivational dysregulations associated with the withdrawal/negative affect and preoccupation/anticipation stages during protracted abstinence. Advances in our understanding of the neurocircuitry and neuropharmacological mechanisms that are involved in the development and maintenance of the withdrawal/negative affect stage using validated animal models have provided viable targets for future medications. Another major advance has been proof-of-concept testing of potential therapeutics and clinical validation of relevant pharmacological targets using human laboratory models of protracted abstinence. This review focuses on future targets for medication development associated with reversal of the loss of reward function and gain in brain stress function that drive negative reinforcement in the withdrawal/negative affect stage of addiction. Basic research has identified novel neurobiological targets associated with the withdrawal/negative affect stage and preoccupation/anticipation stage, with a focus on neuroadaptive changes within the extended amygdala that account for the transition to dependence and vulnerability to relapse.

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Existing and Future Drugs for the Treatment of the Dark Side of Addiction

Koob

Mason²

2016

Annu. Rev. Pharmacol. Toxicol.

104

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The identification of a heuristic framework for the stages of the addiction cycle that are linked to neurocircuitry changes in pathophysiology includes the binge/intoxication stage, the withdrawal/negative affect stage, and the preoccupation/anticipation (craving) stage, which represent neuroadaptations in three neurocircuits (basal ganglia, extended amygdala, and frontal cortex, respectively). The identification of excellent and validated animal models, the development of human laboratory models, and an enormous surge in our understanding of neurocircuitry and neuropharmacological mechanisms have provided a revisionist view of addiction that emphasizes the loss of brain reward function and gain of stress function that drive negative reinforcement (the dark side of addiction) as a key to compulsive drug seeking. Reversing the dark side of addiction not only explains much of the existing successful pharmacotherapies for addiction but also points to vast new opportunities for future medications to alleviate this major source of human suffering.

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Topiramate as Treatment for Alcohol Dependence

Cited by 3 publications

References 2 publications

Development of pharmacotherapies for drug addiction: a Rosetta Stone approach

Development of pharmacotherapies for drug addiction: a Rosetta Stone approach

Emerging pharmacotherapies for alcohol use disorder

Existing and Future Drugs for the Treatment of the Dark Side of Addiction

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