Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment

Background To compare the effects on quality of life (QOL) of oral methadone with sublingual buprenorphine. Methods We performed an open‐label, non‐randomized, two‐site (methadone–buprenorphine) study. During 6 months we assessed the quality of life status of 53 opioid‐dependent patients admitted to a methadone or buprenorphine maintenance programme using the German version (Berlin Quality of Life Profile) of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. Five hundred and thirty urine screening tests were carried out randomly to detect additional consumption. Results Sixty‐seven opioid‐dependent subjects (38 on methadone and 29 on buprenorphine) were enrolled in the study, and 53 completed it (30 subjects treated with buprenorphine and 23 subjects with racemic methadone). The subjects were comparable on all baseline measures. At the first follow‐up (week 8), the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.013) compared with the methadone group. Patients retained in the buprenorphine or methadone programme (week 24) showed no significant differences in all quality of life scores. At the end of the study period, the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.001) and cocaine (P = 0.018) compared with the methadone group. The outcome measures for withdrawal symptoms after 24 weeks of treatment with buprenorphine showed slight advantages in stomach cramps, fatigue or tiredness, feelings of coldness and heart pounding. Conclusions These results suggest that buprenorphine treatment is as effective as methadone regarding effects on quality of life and withdrawal symptoms. Buprenorphine has the potential to reduce the harm caused by drug abuse. Further research is needed to determine if buprenorphine is more effective than methadone in particular subgroups of patients.     

Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial

AIM: The aim of this study is to define the efficacy of dihydrocodeine as an alternative to methadone in the maintenance treatment of opiate dependence. DESIGN: A pragmatic open-label randomized controlled study of patients recommended for opiate maintenance treatment to test equivalence of the two treatment options with follow-up continuing for up to 42 months after recruitment. SETTING: Assessment at either Edinburgh's Community Drug Problem Service or at two general practitioner practices with specialist drug community psychiatric nurses, then with shared care follow-up. PARTICIPANTS: Two hundred and thirty-five subjects (168 male, 67 female) with opiate dependence syndrome were recruited. Subjects selected were suitable for opiate maintenance treatment. Routine treatment was offered throughout. INTERVENTION: Patients were randomized to receive either methadone mixture 1 mg/ml or dihydrocodeine, 30 mg or 60 mg tablets. MEASUREMENTS: The primary outcome measure was retention in treatment. Eight secondary outcomes included total illicit opiate use, reported crime, physical health, mental health, injecting drug use, overdoses, selling drugs and being in education or work. Measures were compared over 42 months follow-up. FINDINGS: There was no difference in groups for retention in treatment at follow-up and there was improvement in all secondary outcomes from baseline. No significant difference in outcomes was found between randomized groups over time. Compliance with randomized treatment differed by randomized group and was affected by experiences in custody during follow-up. Those randomized to dihydrocodeine were more likely to switch treatments. CONCLUSIONS: These results, combined with existing clinical experience, provide evidence that dihydrocodeine is a viable alternative to methadone as a maintenance treatment for opiate dependence. Indirect comparisons with other studies show dihydrocodeine (and methadone) to be superior to placebo.     

A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release

AIMS: This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. DESIGN: A three-group randomized controlled trial was conducted between September 2003 and June 2005. SETTING: A Baltimore pre-release prison. PARTICIPANTS: Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. INTERVENTION: Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). MEASUREMENTS: Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. FINDINGS: Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. CONCLUSIONS: Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.     

A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification

Aims   Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment.
Design   Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups.
Setting   Three psychiatric hospitals in Austria specializing in in-patient detoxification.
Participants   Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence.
Interventions   Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days.
Measurements   Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored.
Findings   Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n  = 102, methadone: n  = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): −12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated.
Conclusions   Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone.     

Physical and mental health in severe opioid-dependent patients within a randomized controlled maintenance treatment trial

Aims To evaluate physical and mental health and compare treatment outcomes in opiate‐dependent patients substituted either with heroin or methadone. Design Twelve‐month open‐label randomized controlled trial. Setting Out‐patient substitution clinics in seven German cities. Participants A total of 1015 opiate‐dependent individuals. Measurements Opiate Treatment Index–Health Scale Score (OTI), Body Mass Index (BMI), serology for infectious diseases such as hepatitis B, C and human immunodeficiency virus as well as tuberculosis, Karnofsky Performance Scale (KPS), electrocardiogram (ECG), echocardiogram, Symptom Checklist 90‐R (SCL‐90‐R), Global Assessment of Functioning (GAF), Modular System for Quality of Life and study medication‐related serious adverse events (SAE). Findings Improvements were found in both heroin and methadone substituted patients regarding OTI, BMI, KPS, SCL‐90‐R, and GAF, but they were more pronounced for the heroin group (analysis of variance, all P = 0.000). The frequency of pathological echocardiograms decreased in the heroin group and increased in the methadone group (χ² test, <0.05). Markers for infectious diseases and frequencies of pathological ECGs did not differ between baseline and 12 months, or between treatment groups. Study medication‐related serious adverse events, all of which were treated successfully, occurred 2.5 times more often in the heroin group. The majority of heroin‐related SAEs (41 of 58) occurred within a few minutes of the injections. Conclusions The integration of severe injection drug users either in methadone or heroin‐assisted maintenance treatment has positive effects on most physical and mental change‐sensitive variables, with heroin showing superior results. Due to medication‐related adverse events, patients should be observed for 15 minutes after a heroin injection.     

Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study

AIMS: To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. DESIGN: Randomized, double-dummy, double-blind, flexible-dosing comparison study. SETTING: Addiction Clinic at the Medical University of Vienna, Austria. PARTICIPANTS: Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group). INTERVENTION: Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos. MEASUREMENTS: Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration. FINDINGS: There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days). CONCLUSION: This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.     

Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: results from a population-based retrospective cohort study

Aims To identify dose‐tapering strategies associated with sustained success following methadone maintenance treatment (MMT). Design Population‐based retrospective cohort study. Setting Linked administrative medication dispensation data from British Columbia, Canada. Participants From 25 545 completed MMT episodes, 14 602 of which initiated a taper, 4183 individuals (accounting for 4917 MMT episodes) from 1996 to 2006 met study inclusion criteria. Measurements The primary outcome was sustained successful taper, defined as a daily dose ≤5 mg per day in the final week of the treatment episode and no treatment re‐entry, opioid‐related hospitalization or mortality within 18 months following episode completion. Findings The overall rate of sustained success was 13% among episodes meeting inclusion criteria (646 of 4917), 4.4% (646 of 14 602) among all episodes initiating a taper and 2.5% (646 of 25 545) among all completed episodes in the data set. The results of our multivariate logistic regression analyses suggested that longer tapers had substantially higher odds of success [12–52 weeks versus <12 weeks: odds ratio (OR): 3.58; 95% confidence interval (CI): 2.76–4.65; >52 weeks versus <12 weeks: OR: 6.68; 95% CI: 5.13–8.70], regardless of how early in the treatment episode the taper was initiated, and a more gradual, stepped tapering schedule, with dose decreases scheduled in only 25–50% of the weeks of the taper, provided the highest odds of sustained success (versus <25%: OR: 1.61; 95% CI: 1.22–2.14). Conclusions The majority of patients attempting to taper from methadone maintenance treatment will not succeed. Success is enhanced by gradual dose reductions interspersed with periods of stabilization. These results can inform the development of a more refined guideline for future clinical practice.     

Melatonin for perceived sleep disturbances associated with benzodiazepine withdrawal among patients in methadone maintenance treatment: a double-blind randomized clinical trial

AIMS: To evaluate the effectiveness of melatonin in attenuating sleep difficulties during benzodiazepine (BDZ) withdrawal. DESIGN: Double-blind cross-over control study. SETTING: Methadone maintenance treatment clinic. PARTICIPANTS: Eighty patients enrolled at a community methadone maintenance clinic recruited to a BDZ withdrawal programme. INTERVENTION: Melatonin (5 mg/day) or placebo: 6 weeks one arm, 1 week washout, 6 weeks other arm. MEASUREMENTS: Urine BDZ; self-reported Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiologic Studies Depression (CES-D) questionnaires administered at baseline, and at 6, 7 and 13 weeks. FINDINGS: Sixty-one patients (77.5% in the 'melatonin first' condition and 75% in the 'placebo first' condition) completed 6 weeks of treatment, showing a similar BDZ discontinuation rate of 11/31 and 11/30, respectively. PSQI scores were significantly lower (indicating better sleep quality) in the 22 patients who discontinued BDZ (8.9 +/- 0.9) than in 39 with urine BDZ (11.2 +/- 0.7, P = 0.04). Sleep quality in patients who continued abusing BDZ improved more in the 'melatonin first' group than in the 'placebo first' group, with no differences in sleep quality improvement in patients who stopped BDZ. CONCLUSION Most improvement in sleep quality was attributed to BDZ discontinuation. Although melatonin did not enhance BDZ discontinuation, it improved sleep quality, especially in patients who did not stop BDZ.     

A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia

Aims The present study aimed to compare the efficacy of levo‐alpha‐acetylmethadol (LAAM) and methadone, as measured by retention in treatment and heroin use, in a randomized trial conducted under naturalistic conditions. Setting This study is the first randomized trial comparing LAAM with methadone in the primary care setting. Participants were recruited through 29 medical practitioners working in specialist and generalist settings in Australia. Participants Existing methadone maintenance patients, aged 18 years and over and able to give informed consent, were randomized to receive either LAAM or methadone. A total of 93 patients participated. Intervention After being trained in the use of LAAM, existing methadone prescribers were then able to determine an individually tailored treatment regimen for each patient. The trial was an open‐label study. Methadone and LAAM dosing was supervised through local community pharmacies. Participation in ancillary services (e.g. counselling) was optional for all patients. The treatment period for the trial was 12 months. Measurements Baseline, 3‐, 6‐ and 12‐month interviews were conducted. Outcome measures were retention in treatment, self‐reported heroin use and serious adverse events. Findings There were no significant differences between LAAM and methadone on retention in treatment, nor heroin use. There was a trend for LAAM patients to have lower heroin use than methadone patients. Of the seven serious adverse events in the LAAM group, three were not drug‐related. There were two dosing errors. Conclusions This study demonstrates (a) the efficacy of LAAM as a treatment for heroin dependence, and (b) the capacity for LAAM to be effectively delivered in primary care settings by trained general practitioners and pharmacists. The next challenge is to resolve outstanding safety concerns with LAAM.     

Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT)

ABSTRACT

Background: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations. Objective: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT). Methods: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit. Results: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml^?1 mg^?1, respectively; p = 0.033]. Conclusion: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.     

Craving predicts opioid use in opioid-dependent patients initiating buprenorphine treatment: A longitudinal study

Background: Few studies have assessed associations between craving and subsequent opioid use. We prospectively evaluated the relative utility of two craving questionnaires to predict opioid use among opioid-dependent patients in outpatient treatment. Method: Opioid-dependent patients (n?=?147) initiating buprenorphine treatment were assessed every two weeks for 3 months. Craving was measured using the: (1) Desires for Drug Questionnaire (DDQ) and (2) Penn Alcohol-Craving Scale adapted for opioid craving (PCS). Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use. Craving assessed at time t was entered as a time-varying predictor of opioid use at time t?+?1. Results: Craving scores plateaued at approximately 2 weeks after initiation of buprenorphine. In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR?=?1.27, 95% CI 1.08; 1.49, p?p?p?>?0.05) or DDQ control (OR?=?0.97, 95%CI 0.85; 1.11, p?>?0.05) scores. Conclusion: Self-reported craving for opioids was modestly associated with subsequent relapse to opioid use among a cohort of patients treated with buprenorphine. Assessment of craving may provide clinical utility in predicting relapse among treated opioid-dependent patients.     

Buprenorphine in pregnant opioid-dependent women: first results of a prospective study

Aim To report results on the prospective follow‐up of 34 pregnant women exposed to buprenorphine maintenance for opiate dependence. Design and setting Prospective multicentre study: all pregnant women receiving buprenorphine as maintenance therapy were included as early as possible during their pregnancy. Participants The pregnant women were recruited from opiate maintenance therapy centres, general practitioner‐networks involved in addiction, maternity hospitals and centres for drug information during pregnancy. Measurements Women: drugs and medications consumed, medical and obstetrical events; offspring: withdrawal syndrome, malformation, neonatal disease. Findings The buprenorphine‐exposed pregnancies resulted in 31 live births, one stillbirth, one spontaneous abortion and one voluntary termination. A neonatal withdrawal syndrome was observed in 13 cases (41.9%) and eight of these babies required opiate treatment. Two neonates had a malformation: a premature ductus arteriosus stricture and a tragus appendix. Conclusion Taken together with other prospective studies, no alarming results were observed concerning pregnancy outcomes. However, further data from the comparative prospective study are required to determine whether buprenorphine can be considered as a good alternative to methadone treatment in pregnant women.