Anton RF. Genetic basis for predicting response to naltrexone in the treatment of alcohol dependence. Pharmacogenomics 9: 655-658
Pharmacogenomics (Impact Factor: 3.22). 06/2008; 9(6):655-8. DOI: 10.2217/14622422.214.171.1245
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- "This issue is highly salient in light of the recent attempt byOslin et al. (2015)to show an effect of the OPRM1 variant As- n40Asp in treatment response to naltrexone. Previous retrospective pharmacogenetic analyses of this SNP have robustly demonstrated that the Asp40 allele was predictive of reduced relapse rates and lower drinking rates in alcohol-dependent individuals treated with naltrexone compared to the Asn40Asn group (Anton, 2008;Chen et al., 2013;Kranzler et al., 2013a;Oslin et al., 2003). However,Oslin et al. (2015)failed to find a significant genotype Â treatment interaction in their sample, suggesting that " it is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence " (Oslin et al., 2015). "
ABSTRACT: Alcohol use disorders (AUDs) represent a significant health burden worldwide. Currently, there are three medications approved by the U.S. Food and Drug Administration for the treatment of AUDs, and other drugs are being prescribed off-label for this purpose. However, response rates for pharmacologic treatment are low, and extant research suggests that treatment effects may partially depend on genetic factors. Personalized medicine, or using a patient's genetics and/or personal history to determine efficacy of treatment prior to prescription, is an emerging tool that will help clinicians treat their patients more effectively and safely. This review systematically discusses current findings from AUD pharmacotherapy trials examining disulfiram, acamprosate, naltrexone, the injectable naltrexone, and topiramate. Furthermore, it presents pharmacogenetics findings associated with these medications in an attempt to further the field of personalized medicine. Research from trials examining AUDs and comorbid major depressive disorder and anxiety disorders is also presented, and pharmacogenetic findings for these treatments are discussed. Lastly, the authors comment on the present and future states of the field of personalized medicine for AUD.
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ABSTRACT: A growing problem of major proportions had been confronting biomedical scientists for many decades. Until solved, this long-neglected problem, the abject failure of the American health care system, presents a gigantic obstacle to the application of the discoveries flowing from neuropsychopharmacological research into deliverable medications utilized by medical practitioners. Although it is recognized that such advances could benefit all of society, both in the United States and globally, progress toward this important goal has not happened. As I noted 5 years ago, 'Unless steps are taken soon to undertake a comprehensive restoration of our system, the profound advances in bio-medical research so rapidly accruing today may never be effectively transformed into meaningful advances in health care for society.' I remain perplexed and frustrated by the reluctance of scientific research societies such as our ACNP to engage their energies and intellect into this most serious issue.
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ABSTRACT: Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted. A total of 150 alcohol-dependent individuals were randomly assigned to a 16-week course of naltrexone alone (50 mg/day [N=50]), naltrexone (50 mg/day) with gabapentin (up to 1,200 mg/day [N=50]) added for the first 6 weeks, or double placebo (N=50). All participants received medical management. During the first 6 weeks, the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group, which had an interval similar to that of the placebo group; had fewer heavy drinking days than the naltrexone-alone group, which in turn had more than the placebo group; and had fewer drinks per drinking day than the naltrexone-alone group and the placebo group. These differences faded over the remaining weeks of the study. Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group, while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group. The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking. This effect did not endure after gabapentin was discontinued.