A Within‐Group Design of Nontreatment Seeking 5‐HTTLPR Genotyped Alcohol‐Dependent Subjects Receiving Ondansetron and Sertraline

Kenna, George A.; Zywiak, William H.; McGeary, John E.; Leggio, Lorenzo; McGeary, Chinatsu; Wang, Shirley; Grenga, Andrea; Swift, Robert M.

doi:10.1111/j.1530-0277.2008.00835.x

Cited by 44 publications

(45 citation statements)

References 53 publications

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“…Also, among participants receiving ondansetron, those with the LL genotype significantly reduced their drinking compared to the LS and SS individuals [80]. These findings are consistent with a pilot human laboratory study [81], where drinking was evaluated under laboratory conditions (i.e. alcohol selfadministration).…”

Section: Ondansetronsupporting

confidence: 80%

“…alcohol selfadministration). Specifically, Kenna and colleagues [81] reported that AD individuals taking .25mg twice a day of ondansetron with the LL genotype reported a significant reduction in drinking. By contrast, the researchers found no correlation in a reduction in drinking with ondansetron in individuals with the LS or SS genotype [81].…”

Section: Ondansetronmentioning

confidence: 98%

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Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Edwards

Kenna²,

Swift³

et al. 2011

CPD

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Harmful alcohol use is a risk factor in more than 60 diseases and injuries resulting in approximately 2.5 million deaths per year worldwide. In the United States (US) and Europe, there are only a few medications approved for alcohol dependence (AD) however, these medications have only been moderately effective and there is a crucial need for more effective treatments. This review briefly summarizes research on currently approved medications for AD, as well as promising medications like topiramate, baclofen and ondansetron. Topiramate is likely the most promising new treatment for AD, however, further research is needed to determine the optimal dose and appropriate length of treatment. Baclofen, a GABA(B) agonist, is a promising medication as a treatment for AD, especially for patients with AD and severe liver disease. Ondansetron has shown promising results as a potential medication for AD, but only within a certain subtype of individuals. This review also discusses more recent findings on other potential pharmacotherapies for AD, such as serotonin-specific reuptake inhibitors (SSRIs; i.e. sertraline), aripiprazole and prazosin, as well as on some examples of other potentially interesting new neuropharmacological targets (i.e. cannabinoid receptors, CRF, NPY, ghrelin). Finally, the present review also discusses the attempts to personalize medication for AD treatment by alcohol typology and pharmacogenetics.

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Section: Ondansetronsupporting

confidence: 80%

Section: Ondansetronmentioning

confidence: 98%

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Edwards

Kenna²,

Swift³

et al. 2011

CPD

Self Cite

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show abstract

“…Nevertheless, this study suggests that ondansetron may reduce alcohol consumption in alcohol-dependent individuals who have the L/L genotype as measured naturalistically and during the ASAE. By contrast there was no support that sertraline reduces alcohol use in individuals who have S/S or S/L genotypes [117].…”

Section: Ondansetronmentioning

confidence: 91%

Medications Acting on the Serotonergic System for the Treatment of Alcohol Dependent Patients

Kenna¹

2010

curr pharm des

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Research suggests that alcoholics show comparatively lower levels of serotonin (5-HT) than non-alcoholics. Medications aimed at increasing synaptic 5-HT have long been studied as potential treatments for alcoholism. Studies with selective serotonin reuptake inhibitors (SSRI) in a heterogeneous population of non-depressed alcoholics have produced inconsistent results. Further exploration involved whether or not treatment of co-morbid alcoholism and depression was a more practical approach. However, even in the presence of co-occurring depression, antidepressants in general lack the power to demonstrate a significant reduction of alcohol use among alcohol dependent patients with carefully diagnosed major depression. Further statistical analysis has also determined that perhaps genotypic and phenotypic variations differ for persons with alcohol dependence including those with or without comorbid alcohol dependence and depression suggesting important subgroups might respond differently to treatments. Clinical trials have also used the anxiolytic buspirone, a 5-HT(1A) partial agonist, as many alcoholics suffer from anxiety. When controlling for baseline anxiety, buspirone was no more effective than placebo for alcoholic patients. Another serotonergic drug, ritanserin, did not demonstrate effectiveness in relapse prevention in alcohol dependence. However, research on the use of the 5-HT(3) antagonist ondansetron for alcohol dependence continues to provide promising results, particularly for patients with early onset alcoholism. As demonstrated by the studies with serotonergics, responses based on individual variables suggest that alcoholics may respond differentially based on various serotonin 5-HT subtypes. Of course, future studies need to further delineate and confirm the differences between these alcoholic subtypes.

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“…Kenna and colleagues [33] studied the serotonin 5-HT 3 receptor antagonist ondansetron and the selective serotonin reuptake inhibitor (SSRI) sertraline in a small (n = 21), within-subjects, laboratory alcohol self-administration study in non-treatment-seeking, alcohol-dependent subjects. Subjects completed three double-blind, self-administration laboratory sessions; each after receiving 3 weeks of one of the medications (ondansetron 0.25 mg twice daily, sertraline titrated to 200 mg daily or placebo).…”

Section: Pharmacogenetic Human Clinical Laboratory Studiesmentioning

confidence: 99%

Pharmacogenetically Driven Treatments for Alcoholism

Arias

Sewell

2012

CNS Drugs

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Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D4 receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject’s age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.

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A Within‐Group Design of Nontreatment Seeking 5‐HTTLPR Genotyped Alcohol‐Dependent Subjects Receiving Ondansetron and Sertraline

Cited by 44 publications

References 53 publications

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Medications Acting on the Serotonergic System for the Treatment of Alcohol Dependent Patients

Pharmacogenetically Driven Treatments for Alcoholism

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