PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Methadone”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

Detection of clinical interactions between methadone and anti-retroviral compounds using an enantioselective capillary electrophoresis for methadone analysis.

A capillary electrophoresis method was developed to detect interactions between methadone and anti-retroviral compounds. Eight subjects, who underwent methadone maintenance treatment in the Province of Alicante (Spain), consented to participate in the present study. Of those, one subject was followed up for 123 days to detect drug-drug interactions. The enantiomers of methadone and those of its main metabolite were conveniently resolved within 4 min using a chiral electrophoresis buffer mixture which consisted of phosphate buffer, pH 5, plus 0.2% highly sulphated-(beta)-cyclodextrin. The effective mobility of the analytes was in the 0.061-0.140 cm(2)/(kV s) range at pH 5. The R-methadone plasma concentration range for seven patients was 91-318 ng/mL, it decreased from 186 to 46 ng/mL in a patient followed-up on commencement of the anti-retroviral therapy, returning to the previous higher levels after progressive dose increases. We conclude that monitoring R-methadone plasma levels can be a useful tool for the dose adjustment of methadone.

Adult↗

Plasma methadone concentrations as an indicator of opioid withdrawal symptoms and heroin use in a methadone maintenance program.

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.

Adult↗

Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels.

A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time.

Adult↗

Self-reported effects of methadone on cigarette smoking in methadone-maintained subjects.

Subjects maintained on methadone evidence a high level of interest in quitting cigarette smoking. Readiness to quit may result, at least partially, from direct pharmacological interactions between methadone and brain nicotinic acetylcholine receptors. The aim of the present study was to assess: (1) self-reported changes in smoking habits after admission to a methadone maintenance treatment (MMT) program; (2) acute effects of methadone administration on smoking behavior in MMT patients. The study was conducted between May and December 2001, in two public outpatient MMT clinics located in Warsaw, Poland. The patients (41 men, 30 women) reported smoking fewer cigarettes after admission to the program. Most subjects (67.6%) changed their favorite brand of cigarettes after admission. Mean nicotine content (mg/cigarette) significantly decreased. On the other hand, the subjects did not report any effects of methadone administration on smoking parameters. The above findings suggest that initiation of MMT is associated with positive changes in smoking behavior. However, these changes may not be related to direct pharmacological interactions between methadone and nicotine.

Adult↗

Methadone toxicity causing death in ten subjects starting on a methadone maintenance program.

Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates.

Adult↗

[Postoperative patient-controlled analgesia is more effective with epidural methadone than with intravenous methadone in thoracic surgery].

OBJECTIVE: To compare the efficacy and side effects of epidural and intravenous methadone for postoperative patient-controlled analgesia (PCA) after thoracic surgery. PATIENTS AND METHODS: A randomized, single-blind trial enrolling 30 patients distributed in 2 groups to receive intravenous methadone (ivPCA group) or epidural methadone (epPCA group). Patients in both groups were administered a loading dose of 0.05 mg.kg-1 followed by infusion of 0.5 mg.h-1. The patients could self-dose 0.5 mg with a lock-out interval of 10 minutes and a maximum of 4 doses per hour. Patient characteristics, type and duration of surgery and fentanyl dose were recorded. Pain was assessed on a visual analog scale (VAS). Level of sedation, respiratory rate and occurrence of nausea, vomiting and pruritus were also recorded over the first 24 hours. RESULTS: The 2 groups were comparable. Pain was greater in the ivPCA group than in the epPCA group in the second hour (VAS 3.93 +/- 1.9 and 2.4 +/- 1.65, respectively; P < .05) and the third hour (VAS 3.57 +/- 1.65 and 1.5 +/- 1.16, respectively; P < .05). The total dose of methadone administered was 25.34 +/- 5.65 mg in the ivPCA group and 18.82 +/- 3.52 mg in the epPCA group (P < .002). There were no significant differences in side effects. CONCLUSIONS: The results suggest that epidural methadone has an intrinsic spinal effect regardless of whether or not there is extra-spinal action arising from syste mic absorption. Epidural methadone provides a more adequate analgesic effect in less time and at a lower dose. Both approaches provide good postoperative analgesia with few side effects.

Adolescent↗

Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-chemical-ionization mass spectrometry.

The (+)-,(-)-, and (+/-)-2H5-methadones, which contained five deuterium atoms in one aromatic ring, were synthesized for use in clinical pharmacological studies and as internal standards. GLC-chemical-ionization mass spectrometry was used to determine plasma and urinary methadone levels by an inverse isotope dilution assay. Plasma drug levels could be determined to 10 pmoles/ml, and urine levels could be measured to 5 pmoles/ml. Plasma methadone levels were examined in several patients undergoing methadone maintenance therapy. These levels generally ranged between 100 and 400 ng/ml (320-1300 pmoles/ml) after an average oral dose of 1 mg/kg/day. The methadone half-life was 28.8 +/- 4.8 hr.

Adult↗

Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels.

In methadone maintenance therapy methadone plasma concentrations of 400 ng/ml are necessary to suppress any further opiate action and to provide stabilized maintenance. In a controlled study we have searched for a differentiation in autonomous activation between patients having low and high methadone plasma levels, using static and dynamic pupillometry and habituation of skin conductance response. Results show that there is no difference in psychophysiological response between patients with high (greater than 400 ng/ml) or low (less than 400 ng/ml) plasma levels of methadone. This indicates that there is no reduction in behavioral arousal in patients with high plasma methadone levels. On the basis of these findings, there is no rationale to maintain patients on plasma levels below 400 ng/ml.

Adult↗

Contingent methadone take-home doses reinforce adjunct therapy attendance of methadone maintenance patients.

Two studies utilized within-subjects designs to determine whether take-home methadone doses can reinforce adjunct therapy attendance of drug abuse patients. These studies varied the reinforcement density and the schedule of methadone take-home doses. In Study 1, patients (n = 10) either could or could not receive a take-home following each therapy session. Study 2 patients (n = 15) could either earn take-homes following each therapy session attended (i.e., 2 take-homes per week) or could earn one take-home dose following each attendance to two consecutive sessions attended. In both studies experimental conditions alternated during three-week blocks of time. Across studies, any reinforcement by take-home doses produced more attendance at therapy sessions than that observed in the no reinforcement condition. Take-home incentive effects were strongest when each of the two weekly therapy sessions was reinforced by a methadone take-home dose. Increased attendance was not associated with reduced drug use, due perhaps to high rates of pre-study drug use and limited therapy duration. Contemporary opioid abusers present with multiple problems that methadone was never intended to treat. The present studies illustrate a method by which methadone treatment can improve the likelihood of delivering other services that may prove effective in treating some of these problems.

Adult↗

Retention of patients who entered methadone maintenance via an interim methadone clinic.

Time in treatment is considered an important predictor of good outcomes for drug abuse treatment. Patient retention would be of particular concern for low-service types of treatment. Interim methadone maintenance was developed as an alternative to waiting lists and as a method of providing HIV risk-reduction services to heroin addicts waiting for treatment, and does not include the regular counseling required in comprehensive methadone treatment. This analysis compares the retention of patients first admitted to an interim methadone clinic versus that of patients admitted directly to a comprehensive methadone clinic. The two groups did not differ with regard to demographic characteristics and drug of abuse at the time of admission. The two groups did not differ with respect to demographics. The three-, six-, and 12-month retention rates of patients first admitted to the interim clinic were 78%, 69%, and 62%, respectively. The three-, six-, and 12-month retention rates for patients admitted directly to a traditional methadone clinic were 84%, 76%, and 68%, respectively. Life-table analysis revealed that the two groups did not differ significantly with regard to retention (p = 0.17). Interim treatment does not appear to adversely affect overall retention in treatment. Three- and six-month retention rates of interim clinic patients fall within the range of six-month nationwide retention rates reported by the GAO. Factors associated with discharge from treatment are examined for both groups.

Adolescent↗

Optimizing response to methadone maintenance treatment: use of higher-dose methadone.

Using signs, symptoms and serum methadone levels to guide evaluation, the authors treated 164 patients in a methadone maintenance program with doses of methadone exceeding 100 mg/d. The mean dose of these higher dose (HD) patients was 211 mg/d (range 110-780 mg/d). A comparison group (C) of 101 patients was randomly selected from the general clinic population (mean dose 65 mg/d). At intake the HD group reported $153/day of heroin use versus $87/day in the C group. The HD group had more patients whose opiate of choice was an oral pharmaceutical (30% versus 2% of the C group). Sixty-three percent of the HD group had comorbid Axis I psychiatric diagnoses compared to 32% of the C group. Response to psychopharmacologic treatment was enhanced by increased methadone dose in HD patients with "refractory" psychiatric disorders. Urine toxicologies described as "before" were collected prior to increase over 100 mg/d in the HD group or at the first routine urine toxicology collection of the calendar year for the C group. These results were compared to the most recent urine toxicologies for both groups ("after"). The percentage of toxicologies positive for illicit drugs in the HD group dropped from 87% "before" to 3% "after". The C group were 54% positive "before" and 37% positive "after". We conclude that doses of methadone in excess of 100 mg/d (range 110-780 mg/d in our sample of 164 patients) are not only safe but necessary to prevent illicit opiate use, stabilize psychiatric symptoms, and diminish abuse of alcohol and benzodiazepines in many patients.

Dose-Response Relationship, Drug↗

Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects.

AIMS: To investigate within- and between-subject variability of the pharmacodynamics and pharmacokinetics of (R)- and (S)-methadone in methadone maintenance subjects at steady-state. METHODS: Six non-holder subjects were studied on three occasions at 7-16 day intervals; doses (20-170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10-12 times over a 24-h inter-dosing interval. All pharmacodynamic data were expressed as the area under the end-point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between- to within-subject variation, with corresponding 95% confidence intervals (CI) for within-subject variation at the average value. RESULTS: Subjects were relatively consistent between occasions, whereas there was much greater between-subject variability (P < 0.02) for all measures. Estimates of the ratio of between- to within-subject variation ranged from 2.2-12.8 for pharmacodynamic measures, and 1.3-7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within-subject measures ranged < or = 2-fold, while this was greater for subjective direct opioid effects (4.2-fold). For CL/F of the active (R)-methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within-subject measures ranging < or = 2-fold. (S)-methadone CL/F demonstrated greater within-subject variability (3.4-fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between- to within-subject variance. CONCLUSIONS: Non-holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1-2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population.

Adult↗

Utilization of plasma and urine methadone concentration measurements to limit narcotics use in methadone maintenance patients: II. Generation of plasma concentration response curves.

Controversy exists still concerning the proper daily dose of methadone required to eliminate illicit narcotics use. To address this, urine methadone and opioid concentrations were measured prospectively (150 maintenance patients, 18 month period, 9250 urine samples) using fluorescence polarization immunoassay. Results demonstrate that current thresholds (EMIT uses 300 micrograms/L) defining opiate positive urines are overly high (FPIA can go as low as 25 micrograms/L), causing severe underestimation of opioid use in the typical clinic. Using this data, plasma methadone concentration and dose response probability curves were generated for illicit opiate use. Results demonstrate a S-shaped, 24 hr trough plasma methadone concentration response curve with effective concentrations, EC90 = 80 micrograms/L, EC98 = 600 micrograms/L. Plotting mean plasma methadone concentration versus dose gives a monotonically increasing function: Conc = 5.367*dose0.858, raw R-squared = 0.967, corrected R-squared = 0.802. Unfortunately, coefficients of variation for plasma concentrations at each prescribed dose are unacceptably large, explaining poor dose response relationships for some patients.

Adult↗

Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use.

OBJECTIVES: The purpose of this study was to examine factors associated with heroin use during methadone maintenance treatment. METHODS: Logistic regression statistical models were used to examine data obtained in a cross-sectional sample of 652 methadone patients. RESULTS: Heroin use during the 3 months prior to interview was shown to be greatest among (1) patients maintained on methadone dosages of less than 70 mg/day (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.3, 3.4) and (2) patients who used cocaine during treatment (adjusted OR = 5.9, 95% CI = 3.8, 9.1). These results were independent of treatment duration, treatment compliance, alcohol use, and socioeconomic factors. Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels. CONCLUSIONS: This study confirms and extends past research showing high-dose methadone maintenance to be important to heroin abstinence. Further investigation of the independent association between heroin use and cocaine use is needed.

Adult↗

Methadone transition treatment: a treatment model for 180-day methadone detoxification.

For those drug addicts who do not meet the United States federal government regulations for methadone maintenance, methadone detoxification remains the primary option for treatment. Studies on the effectiveness of 21-day methadone detoxification, however, report low completion rates and high relapse. Revisions to the standard 21-day detoxification are needed. The research literature suggests that offering psychosocial services within an extended 180-day protocol may be an effective mode of treatment for those addicts who do not meet the requirements for entering methadone maintenance, or do not desire maintenance. Methadone Transition Treatment (MTT) is an innovative treatment organized around this strategy. MTT is transitional in that emphasis is place on working with patients to enter longer-term treatment. To aid the development of similar programs at other institutions, we describe the specific procedures of the MTT model and provide an evaluation of the model based on findings from an initial pilot study.

Adult↗

Methadone maintenance treatment: outcomes from the Otago methadone programme.

AIM: To provide information on methadone treatment outcomes for opiate-dependent individuals. METHODS: Questionnaires and random urine tests were completed for 112 Otago clients comparing outcomes before and during methadone maintenance treatment. RESULTS: Treatment retention rates were high, with 86% of clients remaining on the programme six months or more. The number of clients on benefits reduced by almost 30% during treatment, with employment rates doubling from 19% to 40% (including attendance at educational programmes). For the 89 clients injecting opiates daily at initial presentation, 64% reported no opiate use in the three months prior to review. Of the remaining 36%, opiate use reduced significantly. Rates of sharing injecting equipment reduced by almost 90%. Almost 50% of cannabis users reduced their use from daily to less than daily use. Clients reporting no current use of illicit benzodiazepines increased by 85%. Heavy binge drinking weekly or more reduced by almost 75%. Use of other illicit drugs reduced by almost 90%. Drug-related convictions reduced by almost 60%, while accidental drug overdoses reduced by over 90%. CONCLUSION: The widespread benefits of methadone maintenance treatment demonstrated underline the importance of making quality methadone programmes readily accessible within the health system. Currently, there are long waiting lists and many individuals cannot gain access to active treatment. We believe the health system urgently needs to look at expanding existing services and/or establishing private methadone clinics similar to those in New South Wales.

Adolescent↗

Methadone maintenance treatment can be provided in a primary care setting without increasing methadone-related mortality: the Sheffield experience 1997-2000.

Methadone maintenance treatment has been shown in many studies to reduce mortality and morbidity among heroin users. However, there has been concern that widespread methadone prescribing will lead conversely to an increase in methadone-related deaths. This study in Sheffield shows no increase in methadone-related mortality over a two-year period, during which 400 untreated patients were recruited into primary care methadone treatment in the city.

England↗

Treating heroin addiction: comparison of methadone therapy, hospital therapy without methadone, and therapeutic community.

AIM: To analyze the success of three different treatment modalities for heroin addiction: methadone therapy, hospital therapy without methadone, and therapeutic community. METHODS: Ninety heroin addicts from the city of Split, Croatia, were systematically allocated to three groups, with 30 participants each, according to the addiction treatment modality they underwent or treatment that resulted in the longest abstinence. All participants were heroin addicts for at least 2 years before the treatment. The first group was treated by methadone, the second by hospital therapy, and the third in a therapeutic community. The criterion of the treatment success was minimum two-year heroin abstinence after therapy. RESULTS: After methadone therapy, only a single participant abstained from heroin for more than 2 years, but continued to use soft drugs and alcohol. After hospital therapy, none of the participants abstained from heroin. After therapy in a therapeutic community, 9 participants abstained from heroin; 5 of them continued to use soft drugs and/or alcohol. There was a statistically significant relation between heroin abstinence and therapeutic method (chi-square=16.4236, p<0.001; Fisher's exact test=14.246, p<0.001). CONCLUSION: Treating heroin addiction in a therapeutic community may be a better treatment modality than methadone or hospital therapy.

Adult↗