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Genomes and GenesSpecies | PHARMACOLOGICAL TREATMENTS FOR ALCOHOLISMSummaryPrincipal Investigator: Bankole Johnson Affiliation: University of Virginia Country: USA Abstract: We propose one placebo-controlled, double-blind, outpatient clinical study to examine the efficacy of a 5-HT3 antagonist, ondansetron, and its interaction with several biological and psychosocial factors influencing alcoholism treatment outcome. Ondansetron has been shown to reduce preference and consumption of alcohol in a variety of animal models. Our human laboratory experiments also have shown that ondansetron attenuates some alcohol-induced subjective effects including the desire to drink. In a preliminary clinical trial, ondansetron reduced alcohol consumption by up to 30%. However, the findings of this clinical study were limited because of an inadequate sample size, medication was provided without any psychologically based counseling, there were no female subjects, and follow-up was insufficient. Ondansetron has considerable potential as a therapeutic agent for treating alcoholism. Our principal goal is to evaluate the efficacy of ondansetron in the treatment of alcohol dependent patients receiving standardized cognitive-behavioral coping skills therapy in a double-blind, placebo-controlled clinical trial. Research has suggested that there are two types of alcoholism. Individuals with early onset alcoholism (EOA) characterized by early onset of alcohol related problems, childhood familial vulnerability, greater severity of illness, polydrug abuse, and possibly, increased likelihood of serotonin abnormality. In contrast, individuals with late onset alcoholism (LOA) have a later onset of problem drinking, and a more benign course of illness and outcome. This study will prospectively "type" subjects into EOA or LOA groups to determine whether these alcoholism types differ on treatment outcome. A variety of psychosocial measures will be used retrospectively to examine the validity of this classification scheme. 400 male and female alcoholics who are currently drinking will be assigned to one of eight treatment groups in a 4 x 2 factorial design comparing the EOA groups (placebo, 3.5, 14 and 56 micrograms/Kg b.i.d.) with the LOA groups (placebo, 3.5, 14 and 56 micrograms/Kg b.i.d). EOA and LOA groups will be of similar age and sex distribution. For 12 weeks, all patients will receive daily medication and weekly cognitive-behavioral coping skills therapy using the NIAAA manual. Alcohol consumption will be measured by self-report and alcohol meter readings, and corroborated by serum levels of the carbohydrate deficient transferrin enzyme (CDT) and gamma glutamyl transferase (GGT). The sensitivity of CDT and GGT to changes in alcohol consumption will also be compared. Also, measures of alcohol craving, motivation to change, self-efficacy, decisional balance, social functioning, and changes in mood will be taken weekly. Biochemical tests will determine whether the EOA and LOA groups show differences in serotonergic function or whether individual differences in these variables predict treatment outcome. Clinical outcome will be re-evaluated at 1, 2, 3, 6, 9, and 12 months follow-up post-treatment. This study supports NIAAA's goal to develop effective medications to treat alcoholism. Funding Period: 1998-07-01 - 2000-06-30 more information: NIH RePORT Top Publications
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Platelet serotonin uptake and paroxetine binding among allelic genotypes of the serotonin transporter in alcoholicsMartin A Javors
South Texas Addiction Research and Technology START Center, and Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Prog Neuropsychopharmacol Biol Psychiatry 29:7-13. 2005..Our findings in currently drinking alcoholics support the hypothesis that those with the LL genotype of the 5'-HTTLPR region of the 5-HTT gene have reduced 5-HTT function...- Can serotonin transporter genotype predict craving in alcoholism?Nassima Ait-Daoud
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia 22908 0623, USA
Alcohol Clin Exp Res 33:1329-35. 2009.... - Characterization of a functional polymorphism in the 3' UTR of SLC6A4 and its association with drinking intensityChamindi Seneviratne
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Charlottesville, VA 22911, USA
Alcohol Clin Exp Res 33:332-9. 2009.... - Prediction of serotonergic treatment efficacy using age of onset and Type A/B typologies of alcoholismJohn D Roache
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mailstop 7792, San Antonio, Texas 78229, USA
Alcohol Clin Exp Res 32:1502-12. 2008..Randomized participants underwent 11 weeks of treatment with ondansetron (1, 4, or 16 microg/kg twice daily; n = 67, 77, and 71, respectively) or identical placebo (n = 56), plus weekly standardized group cognitive behavioral therapy... - Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?Bankole A Johnson
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908 0623, USA
Prog Neuropsychopharmacol Biol Psychiatry 32:209-16. 2008..Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone... - Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findingsBankole A Johnson
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, P O Box 800623, Charlottesville, VA 22908 0623, USA
Biochem Pharmacol 75:34-56. 2008..As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored... 
Evaluating readiness and treatment seeking effects in a pharmacotherapy trial for alcohol dependenceJ Kim Penberthy
Center for Addiction Research and Education, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia Health System, Charlottesville, Virginia 22908 0623, USA
Alcohol Clin Exp Res 31:1538-44. 2007..Our goal was to evaluate drinking behavior before initiating a randomized, double-blind pharmacotherapy clinical trial for alcohol dependence...- Treating smoking dependence in depressed alcoholicsNassima Ait-Daoud
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA
Alcohol Res Health 29:213-20. 2006..Additional treatment strategies targeting dually dependent individuals with comorbid psychiatric disorders, including special populations such as women and adolescents, await further investigation... - Topiramate reduces the harm of excessive drinking: implications for public health and primary careJennie Z Ma
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
Addiction 101:1561-8. 2006..Topiramate's potential to decrease the public health consequences of hazardous drinking needs to be established in future long-term studies... - A synopsis of the pharmacological rationale, properties and therapeutic effects of depot preparations of naltrexone for treating alcohol dependenceBankole A Johnson
Department of Psychiatric Medicine, University of Virginia, PO Box 800623, Charlottesville, VA 22908 0623, USA
Expert Opin Pharmacother 7:1065-73. 2006..Naltrel helped reduce relapse and promote abstinence in two samples of alcohol-dependent individuals. Additional efficacy studies are warranted... - Understanding and treating alcohol dependenceBankole A Johnson
Department of Psychiatric Medicine, University of Virginia, Charlottesville, Virginia 22908 0623, USA
Alcohol Clin Exp Res 30:567-84. 2006..Johnson, DSc, MD, PhD; and (5) Differential Effects of Pharmacological Agents on Craving, by Nassima Ait-Daoud, MD... - An overview of medications for the treatment of alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer anticonvulsantsNassima Ait-Daoud
Department of Psychiatric Medicine, University of Virginia, P O Box 800623, Charlottesville, VA 22908 0623, USA
Addict Behav 31:1628-49. 2006..Furthermore, as a class of medication, there appears to be a growing interest in investigating the utility of novel anticonvulsants such as topiramate for the treatment of alcohol dependence... - Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate functionBankole A Johnson
Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA 22908, USA
CNS Drugs 19:873-96. 2005.... - Reductions in and relations between "craving" and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependenceMichael A Dawes
START Center, Division of Alcohol and Drug Addiction, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, The South Texas Addiction Research and Technology Center, San Antonio, TX 78229 3900, USA
Addict Behav 30:1630-7. 2005..These preliminary results suggest that the A-OCDS can be useful as an outcome measure in clinical studies of adolescents with alcohol dependence... - A prospective, open-label trial of ondansetron in adolescents with alcohol dependenceMichael A Dawes
START Center, Division of Alcohol and Drug Addiction, Department of Psychiatry, The University of Texas Health Science Center at San Antonio UTHSCSA, 3939 Medical Drive, Suite 100, San Antonio, TX 78229 3900, USA
Addict Behav 30:1077-85. 2005..Findings of decreased drinking underscore the need for future double-blind, placebo-controlled studies in this adolescent population... - Susceptibility locus in neurokinin-1 receptor gene associated with alcohol dependenceChamindi Seneviratne
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia 22911, USA
Neuropsychopharmacology 34:2442-9. 2009..Additional studies are needed to replicate these results in other samples and to elucidate the mechanism(s) by which these polymorphisms affect NK1R function in the brain...