Characteristics of Quetiapine Misuse Among Clients of a Community-Based Methadone Maintenance Program.

Filed under: Methadone Treatment

J Clin Psychopharmacol. 2012 Aug 24;
McLarnon ME, Fulton HG, Macisaac C, Barrett SP

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Pharmacokinetic-Pharmacodynamic Modeling of Mood and Withdrawal Symptoms in Relation to Plasma Concentrations of Methadone in Patients Undergoing Methadone Maintenance Treatment.

Filed under: Methadone Treatment

J Clin Psychopharmacol. 2012 Aug 24;
Shiran MR, Lennard MS, Iqbal MZ, Lagundoye O, Seivewright N, Tucker GT, Rostami-Hodjegan A

ABSTRACT: The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers’ concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT).Eighty-eight regular subjects at the Sheffield Care Trust Substance Misuse Services were studied. Samples of blood and urine were collected before the daily dose of methadone. Blood samples were taken up to 5 hours after dose. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by liquid chromatography-mass spectrometry. The Total Mood Disturbance Score (TMDS), the Objective Opioid Withdrawal Scale (OOWS), and the Subjective Opioid Withdrawal Scale (SOWS) were used as measures of mood and withdrawal. Population pharmacokinetic/pharmacodynamic analysis and subsequent multiple regression analysis were used to determine the factors influencing the pharmacodynamic effects of methadone.Significant decreases (P ? 0.04) were observed in the scores for the TMDS, SOWS, and OOWS for 5 hours after methadone dosage. The TMDS had returned to baseline by 10 hours after dose (P = 0.98), at which time the SOWS remained significantly below baseline (P = 0.001). Multiple regression analysis revealed that 33% of the overall variation in unbound (R)-methadone EC50 was explained by 3 variables, namely CYP3A activity (9%), age (16%), and sex (8%). Age also accounted for 8% and 9% of the variation in total (rac)- and (R)-methadone EC50.The present study has confirmed that the duration of mood change in the present study was shorter than the effect of methadone in stabilizing withdrawal symptoms. Thus, it is likely that a once-daily dose of methadone, albeit effective for preventing withdrawal, may not be sufficient to improve mood in some patients. Finally, it was established that CYP3A activity, years of dependent use, sex, and age are major determinants of methadone EC50 with respect to TMDS.
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Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.

Filed under: Methadone Treatment

Psychopharmacology (Berl). 2012 Aug 25;
Bogen DL, Perel JM, Helsel JC, Hanusa BH, Romkes M, Nukui T, Friedman CR, Wisner KL

RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D. METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n?=?25) followed prospectively from third trimester of pregnancy to 3 months postpartum. RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase?=?23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase?=?19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.
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Modifying Role of Serotonergic 5-HTTLPR & TPH2 Variants on Disulfiram Treatment of Cocaine Addiction: A Preliminary Study.

Filed under: Methadone Treatment

Genes Brain Behav. 2012 Aug 23;
Nielsen DA, Harding MJ, Hamon SC, Huang W, Kosten TR

Disulfiram is a cocaine pharmacotherapy that may act through increasing serotonin, benefiting patients with genetically low serotonin transporter levels (5-HTTLPR S’ allele carriers) and low serotonin synthesis (TPH2 A allele carriers). We stabilized 71 cocaine and opioid co-dependent patients on methadone for two weeks and randomized them into disulfiram and placebo groups for 10 weeks. We genotyped the SLC6A4 5-HTTLPR (rs4795541, rs25531) and TPH2 1125A>T (rs4290270) variants and evaluated their role in moderating disulfiram treatment for cocaine dependence. Cocaine positive urines dropped from 78% to 54% for the disulfiram group and from 77% to 76% for the placebo group among the 5-HTTLPR S’ allele carriers (F = 16.2; df = 1,301; P <0.0001). TPH2 A allele carriers responded better to disulfiram than placebo (F = 16.0; df = 1,223; P <0.0001). Patients with both an S' allele and a TPH2 A allele reduced cocaine urines from 71% to 53% on disulfiram and had no change on placebo (F = 21.6; df = 1,185; P <0.00001). Source

Methadone-related deaths soar to 15-year high

Filed under: Methadone Treatment

Health minister Anne Milton said councils will be given 'a ring-fenced budget' to help integrate drug treatment and other local services. 'Any death related to misuse of drugs is a tragedy for the victim, their families and their friends,' she said …
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Methadone clinic proposal for South Burlington moves forward

Filed under: Methadone Treatment

The operators of Vermont's largest methadone treatment clinic for heroin and prescription drug addicts are moving forward on a proposal to leave cramped quarters in Burlington for a site in South Burlington. The proposed location at 364 Dorset St. is a …
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Debate over methadone clinic continues

Filed under: Methadone Treatment

To me that is not a treatment,” he said. It is estimated that at least 980,000 people in the United States are currently addicted to heroin and other opiates such as oxycontin, dilaudid and hydrocone. Methadone maintenance treatment is the most …
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