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Biomedical subjects

Bankole A Johnson

Publications and source records attributed to Bankole A Johnson.

50 records · Page 3Linked to original sources
PubMed2004

Uses of topiramate in the treatment of alcohol dependence.

Alcohol dependence is a major cause of morbidity and mortality in the USA and throughout the world. Over the last 10 years there has been an intense interest in developing pharmacotherapies that address the neurochemistry of alcohol dependence. Using a novel pharmacological approach to treating alcohol dependence, topiramate (Topamax, Ortho-McNeil Pharmaceutical) has recently been shown to improve the drinking outcomes of alcohol-dependent individuals. This drug profile highlights the scientific concepts and clinical evidence in the development of topiramate for treating alcohol dependence.

Adult↗
PubMed2004

Relative bioavailability of an extemporaneous ondansetron 4-mg capsule formulation versus solution.

STUDY OBJECTIVE: To compare the relative bioavailability of an extemporaneous ondansetron capsule formulation with that of an identical dose of the commercially available solution formulation. DESIGN: Open-label, randomized, two-way crossover study. SETTING: University-affiliated research laboratory. SUBJECTS: Sixteen (eight men, eight women) healthy, nonsmoking volunteers. INTERVENTION: Participants were randomly assigned to receive a 4-mg dose of either the commercially available ondansetron solution or the extemporaneous ondansetron capsule formulation. Blood sampling was performed over 12 hours after dosing. After a washout period of at least 3 days, each participant was switched to the alternate formulation, and blood sampling was repeated. MEASUREMENTS AND MAIN RESULTS: Ondansetron was well absorbed after administration of both formulations, with the solution achieving a faster rate of drug absorption over the first hour of dosing. After the peak plasma concentration was achieved, the plasma concentration-time curves of both formulations declined at a similar steady rate. There were no significant differences in pharmacokinetic parameters between the two formulations, and the relative bioavailability of the capsule versus the solution formulation was 101%. CONCLUSIONS: Similar concentration-time curves and pharmacokinetic parameters were achieved with the two formulations. The commercially available solution would be a useful alternative formulation for administration of low-dose ondansetron in research and clinical settings.

Adult↗
PubMed2004

Role of the serotonergic system in the neurobiology of alcoholism: implications for treatment.

Preclinical studies have contributed greatly to our understanding of the neurochemical pathways associated with the development and maintenance of alcohol-seeking behaviour. These studies have demonstrated the important role of serotonin pathways, particularly as they relate to dopaminergic function, which mediates alcohol-induced reward associated with its abuse liability. Naturally, this has led to the study of serotonergic agents as treatments for alcoholism.SSRIs do not appear to be effective treatment for a heterogeneous alcoholic group. However, they may be useful as treatment for late-onset alcoholics, or alcoholism complicated by comorbid major depression. Buspirone, a serotonin 5-HT1A partial agonist, does not appear to be an effective treatment for alcoholics without comorbid disease. Buspirone may, however, have some utility for treating alcoholics with comorbid anxiety disorder. The 5-HT2 antagonist ritanserin, at pharmacologically relevant clinical doses, does not appear to be an effective treatment for alcoholism. Ondansetron, a 5-HT3 antagonist, is an efficacious and promising medication for the treatment of early-onset alcoholism. Preliminary evidence suggests that combining the mu antagonist naltrexone with the 5-HT3 antagonist ondansetron promises to be more effective for treating alcoholism than either alone. The differential treatment effect of SSRIs and ondansetron among various subtypes of alcoholic is intriguing. Future research is needed to understand more clearly the molecular genetic differences and the interactions of such differences with the environment that typify a particular alcoholic subtype. Such an understanding could enable us to make comfortable predictions as to which alcoholic subtype might respond best to a particular serotonergic agent, which could then be provided.

Alcoholism↗
PubMed2003

Oral topiramate for treatment of alcohol dependence: a randomised controlled trial.

BACKGROUND: Topiramate, a sulphamate fructopyranose derivative, might antagonise alcohol's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function. We aimed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence. METHODS: We did a double-blind randomised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. Primary efficacy variables were: self-reported drinking (drinks per day, drinks per drinking day, percentage of heavy drinking days, percentage of days abstinent) and plasma gamma-glutamyl transferase, an objective index of alcohol consumption. The secondary efficacy variable was self-reported craving. FINDINGS: At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006), 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them. INTERPRETATION: Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.

Administration, Oral↗
PubMed2003

Current status of carbohydrate deficient transferrin, total serum sialic acid, sialic acid index of apolipoprotein J and serum beta-hexosaminidase as markers for alcohol consumption.

AIMS: The purpose of this paper is to present a brief review of the literature and to summarize the current status of four biochemical markers for alcohol consumption, carbohydrate deficient transferrin (CDT), total serum sialic acid (TSA), sialic acid index of apolipoprotein J (SIJ) and serum beta-hexosaminidase (beta-HEX). FINDINGS: Of these markers, CDT has been the most widely studied, is currently thought to be the most accurate predictor of alcohol consumption, is most readily available and is the only test approved by the FDA for the identification of heavy alcohol use. TSA and SIJ have the potential to be useful markers, but have only recently been discovered, are not readily available and have not yet been studied comprehensively. Finally, the relationship between serum beta-HEX and heavy alcohol consumption has been studied for about 20 years, but the test is not readily available and has not been widely accepted or used as a marker for heavy alcohol consumption. CONCLUSIONS: These markers have the potential to be included in a combination of measurements to provide an accurate, more exact assessment of alcohol consumption in a variety of clinical and research settings.

Alcohol Drinking↗
PubMed2003

Genetics of alcoholism using intermediate phenotypes.

This article represents the proceedings of a symposium at the 2002 meeting of the Research Society on Alcoholism in San Francisco, CA. It was organized by Mary-Anne Enoch and David Goldman and chaired by David Goldman. The presentations were (1) Two functional polymorphisms and their intermediate phenotypes in complex behaviors: COMT/executive cognition and anxiety and HTT/anxiety, by David Goldman; (2) Role of the EEG in determining genetic risk for alcoholism and anxiety disorders, by Mary-Anne Enoch; (3) The response to alcohol as an intermediate phenotype for alcoholism, by Marc A. Schuckit; and (4) Pharmacogenomic approaches to alcoholism treatment: toward a hypothesis, by Bankole A. Johnson.

Alcohol Drinking↗
PubMed2003

Ondansetron reduces mood disturbance among biologically predisposed, alcohol-dependent individuals.

BACKGROUND: Early-onset alcoholics (EOA) differ from late-onset alcoholics (LOA) by developing problem drinking during youth, experiencing severe behavioral problems, having a familial disease history, and possessing a tendency toward subsyndromal mood disturbance, including symptoms of depression, anxiety, and hostility. Subsyndromal mood disturbance is, therefore, an important component of the early-onset syndrome and may be mediated by serotonin dysfunction. Therefore, the serotonin-3 antagonist ondansetron, which has been shown to be effective at improving drinking outcomes and promoting abstinence among EOA, presumably by ameliorating serotonin dysfunction, also may exert its beneficial effects by alleviating mood disturbance among EOA. METHODS: After one lead-in week of single-blind placebo administration, subjects underwent 11 weeks of double-blind outpatient treatment using a 2 x 4 factorial design that examined age of onset (EOA versus LOA) and medication dose (placebo, or ondansetron 1, 4, or 16 microg/kg twice daily) combined with weekly standardized group cognitive-behavioral therapy. The placebo lead-in week was used to adjust for study entrance effects but not for excluding subjects. Assessments of mood were performed by using the overall score and subscales of the Profile of Mood States both at screening and at weekly intervals during the study. RESULTS: Subsyndromal mood disturbance was shown to be an important component of early-onset alcoholism. Ondansetron (16 microg/kg twice daily) showed greater therapeutic efficacy at alleviating symptoms of overall mood disturbance, fatigue, vigor, confusion/bewilderment, and depression among EOA compared with LOA. EOA-associated improvements in mood disturbance seemed to be independent of drinking behavior. CONCLUSIONS: Ondansetron has been shown to be an effective treatment for early-onset alcoholism. Ondansetron's ability to improve symptoms of depression, anxiety, and hostility among EOA may make an additional contribution to its therapeutic effect. Mechanistic studies are needed to delineate more clearly the relationship between serotonin dysfunction and pathophysiology among various subtypes of alcohol-dependent individuals.

Adult↗
PubMed2003

Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects.

We examined kinetic and dynamic factors to determine the pharmacological and behavioral safety and tolerability of low versus high doses of an opiate antagonist, naltrexone (50 mg/day vs. 100 mg/day), and acamprosate (2 g/day vs. 3 g/day), a functional N-methyl-D-aspartate receptor antagonist, both independently and combined, among non-treatment-seeking, alcohol-dependent individuals. This double-blind, double-dummy, placebo-controlled, randomized, 23-day, four-way crossover study involved 23 subjects assigned to one of four groups. Placebo washout (phase I) preceded phase II, where subjects received low-dose or high-dose naltrexone or acamprosate. In phases III and IV, the alternative medication type at its lower and higher doses, respectively, was administered with continuation of the phase II medication. Predetermined behavioral, performance, and pharmacological criteria determined significant pathological change from baseline (phase I). Case records were reviewed. Criterion-significant increases in symptoms from baseline with monotherapy included nervousness and fatigue with 3 g acamprosate and somnolence and headache with 50 mg and 100 mg naltrexone, respectively. Combined treatment at various doses evinced anger, depression, somnolence, nervousness, diarrhea, and headache. Notably, for all but one subject who dropped out, increased symptoms did not produce any remarkable clinical deterioration. Naltrexone administration significantly increased plasma acetylhomotaurine (i.e., acamprosate) levels, presumably by prolonging gastric emptying. The level of neither plasma acetylhomotaurine nor plasma 6-beta naltrexol (i.e., naltrexone's metabolite) predicted adverse-event frequency. Naltrexone and acamprosate, both alone and in combination at the tested doses, were behaviorally and pharmacologically safe. Adverse events were infrequent, were of moderate intensity, and resolved with reassurance and symptomatic treatment. More side effects were noted with the combination of medications than with either medication alone. Naltrexone administration significantly increased plasma acamprosate levels.

Acamprosate↗
PubMed2003

The role of serotonergic agents as treatments for alcoholism.

Serotonergic agents remain an important area of pharmacologic study as treatments for alcoholism. Selective serotonin reuptake inhibitors (SSRIs) do not appear to be efficacious at treating a heterogeneous alcoholic group. SSRIs may, however, possess utility in treating later-onset alcoholics and alcoholism that is complicated by co-morbid major depression. The 5-HT(1A) partial agonist, buspirone, does not appear to be an efficacious treatment for alcoholics without co-morbid disease. Buspirone may, however, possess some utility in treating alcoholics with co-morbid anxiety disorder. Ritanserin, a 5-HT(2) antagonist, does not appear to be an efficacious treatment for alcoholism at pharmacologically relevant clinical doses. Ondansetron, a 5-HT(3) antagonist, is an efficacious and promising medication for the treatment of earlier-onset alcoholism. The differential treatment effect of SSRIs and ondansetron among various subtypes of alcoholics is intriguing. Future research is needed to more clearly understand the biopsychosocial differences that typify a particular alcoholic subtype. This type of understanding could develop our ability to make reasonable predictions as to what alcoholic subtype would respond best to a particular serotonergic agent, which could then be provided.

Alcoholism↗
PubMed2002

Ondansetron reduces the craving of biologically predisposed alcoholics.

RATIONALE: Early onset alcoholics (EOA) differ from late onset alcoholics (LOA) by having greater serotonergic abnormality, familial history, and a range of antisocial behaviors. Previously, we showed that ondansetron, a selective 5-HT3 antagonist, effectively treated EOA. Proximate motivational drives such as craving could have determined drinking behavior. We therefore investigated whether ondansetron treatment would reduce alcohol craving significantly among EOA. OBJECTIVES: We tested the hypothesis that the craving outcomes of EOA, compared with LOA, would be differentially improved by ondansetron. We also tested the prediction that craving would be significantly correlated with drinking behavior. METHODS: We studied a cohort of 253 out of 321 enrolled alcohol dependent subjects. These 253 subjects were entered into a 1-week lead-in single-blind placebo period followed by 11 weeks of double-blind outpatient treatment. Study design was a 2 (EOA versus LOA)x 4 medication dose (placebo, or ondansetron 1, 4, or 16 microg/kg b.i.d)x 13 (visits) factorial analysis of variance. Craving was measured at each visit using seven visual analogue scales. Subjects received 12 weekly sessions of standardized group cognitive behavioral therapy. RESULTS: Data reduction by factor analysis of the visual analog scale items yielded one dimension, overall craving. Ondansetron 4 microg/kg b.i.d. reduced overall craving significantly among EOA. In contrast, ondansetron (1 microg/kg b.i.d.) increased craving significantly in LOA. Decreased overall craving was positively correlated with reduced drinking and negatively associated with increased abstinence. CONCLUSIONS: Compared with placebo, ondansetron (4 microg/kg b.i.d.) was associated with significant reductions in overall craving in EOA but not LOA, presumably by ameliorating serotonergic abnormality.

Adult↗
PubMedDate not supplied

The role of anxiety in predicting drinking behaviour.

AIMS: We investigated whether reduced anxiety predicted improved drinking outcomes over and above age of onset and ondansetron treatment among alcoholics enrolled in a clinical trial. METHODS: Study design was a 2 (early onset alcoholics versus late onset alcoholics) x 4 (placebo and ondansetron 1, 4 and 16 micro g/kg twice daily) factorial randomized clinical trial during which all participants received weekly group cognitive behavioural therapy. Using weighted least squares regression, we examined the effects of ondansetron dose, age of onset, pre-treatment drinking and anxiety level (measured by Profile of Mood States) on end-state drinking behaviour. Our previous studies have demonstrated that ondansetron dose, age of onset and pre-treatment drinking influence end-state drinking behaviour. RESULTS: and conclusions: The present study added to our previous knowledge, indicating that when change in anxiety level was included as a predictor of end-state drinking, it also accounted for a significant proportion of the variance. Those who experienced decreases in anxiety during the treatment reported fewer drinks per day at their last visit compared with those who reported increases in anxiety.

Adult↗
PubMedDate not supplied

Pharmacotherapeutic trials in adolescent alcohol use disorders: opportunities and challenges.

Medications as adjuncts to psychosocial treatments for adolescent alcohol use disorders hold the promise of improved efficacy over psychosocial treatments alone. Specific components should be included in the design and implementation of these medication studies. Included should be assessment of the developmental risks of the chosen medication, consideration of short-term effects on the clinical disorder, factors affecting compliance and retention, age-specific pharmacokinetics, and systematic safety monitoring. A risk-benefit analysis should be conducted on the potential benefits of the medication to decrease alcohol use versus the potential long-term effects of medication use on brain development. To select clinically meaningful subtypes of adolescents with alcohol use disorders for medication trials, classification systems should be derived from multi-factorial models of complex neurodevelopmental disorders. Multi-factorial models will be required to select samples wherein specific gene-gene and gene-environment interactions predict medication treatment response. In samples of adolescents with alcohol use disorders, clinically meaningful subtypes are likely to have differential medication treatment response as a function of age of onset, family history of disorder, and comorbid psychopathology. Findings from preclinical and treatment studies in adults, along with pilot treatment findings in adolescents, suggest that particular serotonergic agents, opioid antagonists, and agents that modulate excitatory amino acids and GABAergic transmission might be effective. Future medication trials for adolescents with alcohol use disorders should use specific combinations of medications, based on specific hypotheses involving key neurotransmitter systems that putatively modulate treatment response. Combinations of medications may have additive effects on particular neurotransmitter systems or synergistic effects across two or more neurotransmitter systems, to further decrease alcohol consumption when compared with single-agent treatment.

Alcoholism↗
PubMedDate not supplied

Pharmacists' and technicians' perceptions and attitudes toward dispensing buprenorphine/ naloxone to patients with opioid dependence.

OBJECTIVE: To assess the perceptions and attitudes of pharmacists and pharmacy technicians involved in an office-based opioid dependence treatment program using buprenorphine/naloxone. DESIGN: Cross-sectional attitudinal assessment. SETTING: Community, outpatient hospital, and clinic pharmacies. PARTICIPANTS: Pharmacists and technicians participating in a clinical trial of opioid dependence treatment using buprenorphine/naloxone. INTERVENTION: Written and telephone surveys followed by interviews with open-ended items. MAIN OUTCOME MEASURES: Attitudes and perceptions regarding opioid-dependent patients and use of buprenorphine/naloxone for treatment of opioid dependence. RESULTS: Pharmacies in seven states (New York, Virginia, Illinois, Florida, Texas, California, and Washington) participated in the clinical trial. A total of 40 pharmacists and pharmacy technicians responded to the initial written survey, representing 27 of the 32 pharmacies (84%). Follow-up interviews were obtained from one individual at 30 of those pharmacies (93.8%). Most pharmacy personnel (77.5%) involved with this study were not more concerned about theft or break-ins and would be willing to participate in opioid dependence treatment as the medication became available commercially (70%). The majority of respondents (85%) indicated that patients did not cause problems at their pharmacies. Compared with their experiences in administering other narcotic medications, most respondents did not express increased concern regarding prescription forgery (75%) or diversion (80%) of buprenorphine/naloxone. CONCLUSION: The majority of respondents expressed positive attitudes and perceptions regarding patients treated for opioid dependence with buprenorphine/naloxone.

Attitude of Health Personnel↗