Tag Archives: topiramate

The Treatment of Alcohol Dependence: the utility of genetic testing.

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DNA double helixOne goal in modern medicine is to use genetics to determine the best treatment strategy for an individual patient. A simple, cheap genetic test which predicts response to a particular treatment has clear utility for patients.

To date, psychiatry has lagged behind general medicine, no doubt due to the complexity of CNS tissue and the sheer number of components involved in CNS processing, but the picture is changing. One particular area of interest is the treatment of alcohol dependence.

The pharmacogenomics of topiramate

The drug topiramate started off as an anticonvulsant, but was also been found to be effective in reducing alcohol consumption in heavy drinkers. An American study has advanced our knowledge. Natural variation in the DNA coding for a type of glutamate receptor called the kainite receptor was shown to determine if problem drinkers responded to topiramate treatment.

In those carrying the CC variant at rs2832407, topiramate (200mg/d) markedly reduced the number of heavy drinking days compared to placebo (Fig. 1). Heavy drinking decreased from 5 days per week to approximately 1 day per week in CC subjects treated with topiramate.

topiramate v placebo for heavy drinking by genotype

In a 12 week study, heavy drinkers with the CC genotype at rs2832407 in the kainite receptor showed significant reductions in heavy drinking when treated with topiramate.

 

Definite study

A larger study is now underway, hoping to confirm the initial genetic findings. If the result is replicated, genetic testing may translate to routine clinical practice for heavy drinkers considering topiramate treatment.

This would represent a significant advance in the management of alcohol disorders.

Baclofen & Topiramate for Alcohol Dependence?

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wine bottles

A new paper appraises promising strategies for the treatment of drug addiction in general. The authors consider agents which target GABA transmission, ion-channels and the emerging technique of repetitive transcranial magnetic stimulation (rTMS). In their elegant review of the field, perhaps the most noteworthy findings involve the treatment of alcohol dependence with either baclofen or topiramate.

Baclofen

Baclofen is a GABA-b agonist, which has been used in neurology for years. Several open-label studies, and 2 out of 3 randomised controlled trials (RCTs) have suggested that baclofen is effective in alcohol dependence by reducing cravings and promoting abstinence. Baclofen is safe (even in subjects with liver cirrhosis) and is generally well tolerated with sedation being the most notable side-effect. Higher doses of baclofen appear to be more effective, but this needs confirmation in further RCTs.

Topiramate

Topiramate enhances inhibitory and dampens excitatory currents in neurons, and has been used as an anticonvulsant for years. In 2 relatively large RCTs, topiramate was effective in alcohol dependence, by reducing cravings and the severity of dependence, and improving physical and psychosocial outcomes. Topiramate is generally well tolerated, although cognitive side effects can occur, and it should be avoided in pregnancy.

The full paper can be read here.