The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency.

Front Psychiatry. 2012; 3: 109
Spellicy CJ, Kosten TR, Hamon SC, Harding MJ, Nielsen DA

Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2?weeks and then randomized into disulfiram (250?mg/day, N?=?32) and placebo groups (N?=?35) for 10?weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10?weeks of the study (N?=?56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N?=?32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p?=?0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N?=?24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81-69% (p?=?0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630.
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Low rates of hepatitis C testing among people who inject drugs in Thailand: implications for peer-based interventions.

J Public Health (Oxf). 2013 Jan 18;
Ti L, Kaplan K, Hayashi K, Suwannawong P, Wood E, Kerr T

BACKGROUND: Regular testing for hepatitis C virus (HCV) provides an opportunity for HCV prevention and treatment efforts. In Thailand, the barriers and facilitators of HCV testing among people who inject drugs (IDU) are not known. METHODS: Using data derived from the Mitsampan Community Research Project between July and October 2011, we assessed the prevalence and factors associated with ever having been tested for HCV antibodies using bivariate statistics and multivariate logistic regression. RESULTS: Among 427 participants, 141 (33.0%) reported a history of HCV antibody testing. In multivariate analyses, factors positively associated with receiving an HCV antibody test included higher than secondary education [adjusted odds ratio (AOR) = 2.20; 95% confidence interval (CI): 1.35-3.64], binge drug use (AOR = 1.81; 95% CI: 1.12-2.93), methadone treatment enrollment (AOR = 3.47; 95% CI: 1.85-6.95) and having received peer-based education on HCV (AOR = 4.22; 95% CI: 2.66-6.77). CONCLUSIONS: We found one-third of Thai IDU in our sample reporting a history of HCV testing. The finding that IDU who received peer-based HCV education were more likely to access HCV testing provides evidence for the value of peer-based interventions for this population.
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Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study.

Drug Alcohol Depend. 2013 Jan 17;
Dreifuss JA, Griffin ML, Frost K, Fitzmaurice GM, Potter JS, Fiellin DA, Selzer J, Hatch-Maillette M, Sonne SC, Weiss RD

BACKGROUND: Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. METHODS: A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. RESULTS: In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. CONCLUSIONS: This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients’ response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone.
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Respiratory effects of diazepam/methadone combination in rats: A study based on concentration/effect relationships.

Drug Alcohol Depend. 2013 Jan 14;
Chevillard L, Declèves X, Baud FJ, Risède P, Mégarbane B

BACKGROUND: Methadone may cause respiratory depression and fatalities. Concomitant use of benzodiazepines in methadone-treated patients for chronic pain or as maintenance therapy for opiate abuse is common. However, the exact contribution of benzodiazepines to methadone-induced respiratory toxicity remains debatable. METHODS: We investigated the respiratory effects of the combination diazepam (20mg/kg)/methadone (5mg/kg) in the rat, focusing on methadone concentration/effect relationships. Respiratory effects were studied using arterial blood gases and whole-body plethysmography. Plasma concentrations of both R- and S-methadone enantiomers were measured using high-performance liquid chiral chromatography coupled to mass spectrometry. To clarify mechanisms of diazepam/methadone interaction, methadone metabolism was investigated in vitro using rat liver microsomes. RESULTS: Diazepam/methadone co-administration significantly increased methadone-related effects on inspiratory time (p<0.001) but did not significantly alter the other respiratory parameters when compared with methadone alone, despite significant increase in the area under the curve of plasma R-methadone concentrations measured during 240min (p<0.05). Diazepam/methadone co-incubation with microsomes in vitro resulted in a significant inhibition of methadone metabolism (p<0.01), with 50%-inhibitory diazepam concentrations of 25.02±0.18?mol/L and 25.18±0.23?mol/L for R- and S-methadone, respectively. CONCLUSION: We concluded that co-administration of high-doses of diazepam and methadone in rats is not responsible for additional respiratory depression in comparison to methadone alone, despite significant metabolic interaction between the drugs. In humans, although our experimental data may suggest the relative safety of benzodiazepine/methadone co-prescription, physicians should remain cautious as other underlying conditions may enhance this drug-drug interaction. HubMed – Methadone

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