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. Retention in a low-threshold methadone maintenance program. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. Baclofen for maintenance treatment of opioid dependence: a randomized double-blind placebo-controlled clinical trial [ISRCTN32121581]. Predictors of patient retention in a newly established methadone maintenance treatment programme. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. A controlled trial of buprenorphine treatment for opioid dependence.
Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment.
                Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups.
                Three psychiatric hospitals in Austria specializing in in-patient detoxification.
                Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence.
                Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days.
                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.
                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.
                Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone. In 370 opioid-dependent patients included consecutively in a low-threshold methadone maintenance program, the effect of different variables on the retention rate was assessed. The variables included the patients' age, sex, family situation, employment status, length of heroin use, current route of drug consumption, previous treatments, current consumption of cocaine, alcohol and benzodiazepines, needle sharing, HIV serostatus and methadone dose. The retention rate after 2 years of methadone maintenance was 72%. Dose of methadone > 80 mg/day, age > 30 years, living with family or stable partner and non-current use of alcohol were significant predictive variables for retention. 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.
                Patients were randomized to four dosage groups and treated double-blind.
                Twelve outpatient opiate maintenance treatment centers throughout the United States.
                Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment.
                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.
                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.
                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.
                The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy. Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance.
                Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period.
                Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted.
                Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage. The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence.
                We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids.
                The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes.
                Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283 [ClinicalTrials.gov].).
                Copyright 2006 Massachusetts Medical Society. Results of preclinical studies suggest that the GABA(B) receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence.
                A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory.
                Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different.
                The results support further study of baclofen in the maintenance treatment of opioid dependence. To identify predictors of patient retention in methadone maintenance.
                Prospective study.
                Methadone maintenance treatment programme newly established in Geneva, Switzerland.
                All patients who initiated treatment between February 1991 and January 1995.
                Baseline patient characteristics, dose of methadone, year of enrollment and retention in treatment.
                Overall, 111 patients contributed 164.4 person-years of follow-up. The retention rate was 84% after 12 months. In multivariate analysis, the risk of dropping out was significantly higher for patients who had been using opioids for < or = 7 years (relative hazard (RH) 3.0, 95% confidence interval (CI) 1.2-7.4), and for patients who had no stable income at baseline (RH 3.3, 95% CI 1.2-9.1). Dropouts were less frequent at the highest doses of methadone (65-110 mg/day, RH 1.0) than at middle doses (45-60 mg/day, RH 2.0, 95% CI 0.7-5.5) but, quite unexpectedly, dropouts were least likely at the lowest doses (15-40 mg/day, RH 0.5, 95% CI 0.1-1.8). Dropouts were more likely among patients who enrolled in the first (RH 6.2, 95% CI 2.3-16.7) and second (RH 1.9, 95% CI 0.6-5.6) years of the programme, compared with subsequent years (RH 1.0).
                Patients who have a long history of drug use and who have a stable income were more likely to stay in methadone maintenance treatment. Independent of patient characteristics, retention improved dramatically in the first years of programme functioning, suggesting that patient retention is a sensitive indicator of programme performance. With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients. To assess the efficacy of buprenorphine for short-term maintenance/detoxification.
                A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase.
                Outpatient facilities at the Addiction Research Center, Baltimore, Md.
                One hundred sixty-two volunteers seeking treatment for opioid dependence.
                In addition to the medication, counseling using a relapse prevention model was offered but not required.
                Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence.
                Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups.
                Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.
The present review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance because only three studies meeting our inclusion criteria have been identified. Two studies suggested a possible reduction of opioid use in people taking SROM. In another study, the use of SROM was associated with fewer depressive symptoms. Retention in treatment was not significantly different among compared interventions while the adverse effects were more frequent with the people given SROM.