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.     

Slow-release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence

AIMS: To evaluate slow-release oral morphine (SROM) as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. DESIGN: Open-label crossover study. SETTING: Out-patient methadone maintenance programme. PARTICIPANTS: Eighteen methadone maintenance patients. Intervention Participants were transferred from methadone to SROM (once-daily Kapanol trade mark ) for approximately 6 weeks before resuming methadone maintenance. MEASUREMENTS: Patient outcomes were assessed (1) during the transition between medications (dose requirements, withdrawal severity) and (2) after at least 4 weeks on a stable dose of each drug (treatment preference, patient ratings of treatment efficacy and acceptability, drug use, health, depression and sleep). FINDINGS: Transfer from methadone to SROM was associated with relatively mild withdrawal for the first 5 days; the final mean SROM : methadone dose ratio was 4.6 : 1. Compared to methadone, SROM was associated with improved social functioning, weight loss, fewer and less troublesome side-effects, greater drug liking, reduced heroin craving, an enhanced sense of feeling 'normal' and similar outcomes for unsanctioned drug use, depression and health. The majority of subjects preferred SROM (78%) over methadone (22%). CONCLUSIONS: These findings provide justification for further evaluation of SROM as a maintenance pharmacotherapy for opioid dependence.     

Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients

Aims To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet. Design Patients were randomized to receive buprenorphine or methadone over a 13‐week treatment period in a double‐blind, double‐dummy trial. Setting Three methadone clinics in Australia. Participants Four hundred and five opioid‐dependent patients seeking treatment. Intervention Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1–6, patients were dosed daily. From weeks 7–13, buprenorphine patients received double their week 6 dose on alternate days. Measurements Retention in treatment, and illicit opioid use as determined by urinalysis. Self‐reported drug use, psychological functioning, HIV‐risk behaviour, general health and subjective ratings were secondary outcomes. Findings Intention‐to‐treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13‐week period (Wald χ² = 4.371, df = 1, P = 0.037), but not separately for the single‐day or alternate‐day dosing phases. There were no significant between‐group differences in morphine‐positive urines, or in self‐reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate‐day dosing were maintained in alternate‐day dosing. Conclusions Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too‐slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.     

Switching between methadone and morphine for maintenance treatment of opioid dependence: impact on pain sensitivity and mood status

Methadone maintenance is associated with hyperalgesia and elevated mood disturbance-effects opposite to those induced by acute opioid administration, which may undermine outcomes during substitution therapy. This study examined the impact of switching between methadone and slow-release morphine on pain sensitivity and mood status in 14 methadone maintenance patients using an open-label crossover design. Pain responses were nearly identical for each drug. Patients reporting inadequate withdrawal suppression on methadone showed greater mood stability when transferred to morphine, but overall mood disturbance levels did not differ between drugs. Hyperalgesia and mood disturbance cannot be resolved by changing from methadone to morphine maintenance.     

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.     

Detection of illicit opioid and cocaine use in methadone maintenance treatment.

Urine toxicology is the gold standard for estimating the prevalence of illicit drug use in methadone maintenance treatment (MMT). The frequency of urine testing may be crucial for establishing accurate use rates. Infrequent testing may lead programs to undercount active drug users and to target interventions too narrowly. This study compared results from frequent testing (twice per week) versus less frequent testing of 166 patients at four MMT programs. As part of a research study, all patients were tested by research staff for opioid and cocaine use twice per week on a fixed schedule for 10 weeks. During the same period, the four MMT programs tested the patients according to their standard protocols, approximately weekly (one program) or every 3-4 weeks (three programs). The research tests identified approximately 50% more illicit opioid users and 70% more cocaine users than the less frequent program tests. Patients who were drug positive according to the research tests but drug negative according to the program tests tended to be infrequent users. The data suggest that standard urine testing practices in MMT programs may result in underestimates of the prevalence of opioid and cocaine use. More frequent testing, even for time-limited periods, should produce more accurate depictions of drug use prevalence and help indicate the direction of interventions.     

Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial

Aims. To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels . Design. Patients were randomized to four dosage groups and treated double-blind . Setting. Twelve outpatient opiate maintenance treatment centers throughout the United States . Participants. Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment . Intervention. Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session . Measurement. Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events . Findings. Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids . Conclusions. The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.     

Ventricular arrhythmias in patients treated with methadone for opioid dependence

Purpose  

Over the last decade, there has been a significant rise in reported cases of methadone induced QT prolongation (QTP) and Torsades de Pointes (TdP) in patients treated for opioid dependence. Optimal management of these patients is challenging.     

Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment

Maintenance therapy with methadone or buprenorphine‐based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine‐based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients. (Am J Addict 2010;00:1–12)     

Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review

AIMS: To determine the efficacy of naltrexone in reducing illicit opioid use and the potential moderating role of treatment retention. DESIGN: First, randomized controlled trials (RCTs) comparing the regimens of treatment using the opioid antagonist, naltrexone, with controls were analysed by meta-analysis for treatment effect with regard to a range of outcome criteria. The degree of heterogeneity was also determined. The moderating effect of other interventions during naltrexone maintenance was then estimated, particularly with regard to their effect on treatment retention. PARTICIPANTS: Fifteen studies involving 1,071 patients were found. MEASUREMENTS: All available outcomes were analysed in 10 studies of naltrexone versus control (seven placebo) and six studies of randomized psychosocial/psychopharmacological interventions. FINDINGS: Significant heterogeneity was found in the efficacy of naltrexone. Level of retention in treatment was found to be a moderator, explaining most of the heterogeneity found. Overall, naltrexone was significantly better than control conditions in reducing the number of opioid-positive urines. This effect was only present in the high retention subgroup for differences in retention. Contingency management (CM) increased retention and naltrexone use, resulting in a reduced number of opioid-positive urines. CONCLUSION: Retention is important to the effect of naltrexone in treating opioid dependence. Contingency management is a promising method of increasing retention.     

Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients

ABSTRACT

Background: Benzodiazepine use disorders are a common clinical problem among methadone maintenance treatment patients and have adverse effects on clinical outcomes. Objectives: To evaluate gabapentin for the outpatient treatment of benzodiazepine abuse or dependence in methadone maintenance patients. Methods: Participants (n = 19) using benzodiazepines at least 4 days per week were enrolled into an 8-week randomized double-blind placebo-controlled outpatient pilot trial. All participants received a manual-guided supportive psychotherapy aimed to promote abstinence. Study medication was titrated over a 2-week period to a maximum dose of gabapentin 1200 mg or placebo three times a day. Benzodiazepine use was assessed using urine toxicology confirmed self-report. Benzodiazepines were not provided as part of study participation; participants were provided guidance to gradually reduce benzodiazepine intake. Results: Sixteen participants had post-randomization data for analysis. Retention at week eight was 50%. The mean dose of gabapentin achieved by titration was 2666 mg/day (SD = ± 1446). There were no significant between group differences on benzodiazepine use outcomes (amount benzodiazepine per day [Mann-Whitney U = 27, p = 0.745], abstinent days per week [U = 28, p = 0.811]) and Clinical Instrument Withdrawal Assessment (CIWA)-benzodiazepines scale (U = 29.0, p = 0.913). One participant in the gabapentin group discontinued study medication because of peripheral edema. Two participants in the placebo group requested admission for inpatient detoxification treatment. Conclusion: In outpatient methadone-maintained patients with benzodiazepine use disorder, gabapentin did significantly decrease benzodiazepine use relative to placebo. The small sample recruited for this trial may have limited the ability to detect a group difference.     

Optional versus mandatory psychotherapy in methadone maintenance

Treatment outcomes of 23 methadone maintenance patients who were offered optional psychotherapy were compared with those of 31 methadone maintenance patients who received mandatory psychotherapy. There were no statistically significant differences in pretreatment characteristics between the optional group and the mandatory group. Patients in the optional group received less than half as many hours of therapy as patients in the mandatory group. Differences between the two groups in retention, employment, illicit drug use, and arrests were nonsignificant during a 1-year study period. The findings were compatible with those of most previous studies of the effectiveness of psychotherapy in methadone maintenance, which suggest that outcomes with or without psychotherapy do not differ significantly.