1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients. Double-blind randomized trial of buprenorphine and methadone in opiate dependence. A controlled trial of buprenorphine treatment for opioid dependence. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Buprenorphine: a controlled clinical trial in the treatment of opioid dependence. Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants. Feasibility of buprenorphine and methadone maintenance programmes among users of home made opioids in Ukraine. Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users. Buprenorphine treatment for opioid dependence: the relative efficacy of daily, twice and thrice weekly dosing. Buprenorphine versus methadone maintenance for opioid dependence. A placebo-controlled study of high dose buprenorphine in opiate dependents waiting for medication-assisted rehabilitation in Oslo, Norway. Prognostic factors in Buprenorphine- versus methadone-maintained patients. Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Randomized clinical trial to compare the effects of methadone and buprenorphine on the immune system in drug abusers. Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects. Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine.
The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.
                40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.
                1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio 58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.
                The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin. The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts. To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks.
                Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study.
                Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna.
                Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment.
                Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase.
                Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis.
                The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04).
                The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol. Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use.
                A total of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report.
                There were significant effects of maintenance treatment on rates of illicit opioid use, but no significant differences in treatment retention or the rates of cocaine use. The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments.
                The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use, but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use. 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 aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment. This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages. 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. 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. 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.
                Patients were randomized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind, double-dummy trial.
                Three methadone clinics in Australia.
                Four hundred and five opioid-dependent patients seeking treatment.
                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.
                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.
                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 chi 2 = 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.
                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. This study compared the efficacy of buprenorphine and methadone in the treatment of opioid dependence.
                Participants (N = 164) were relatively treatment-naive, opioid-dependent applicants to a 26-week treatment program who were randomly assigned to either methadone or buprenorphine treatment. Dosing was double-blind and double-dummy. Patients were stabilized on a regimen of either methadone, 50 mg, or buprenorphine, 8 mg, with dose changes possible through week 16 of treatment. Urine samples were collected three times a week, and weekly counseling was provided.
                Buprenorphine (mean dose = 8.9 mg/day) and methadone (mean dose = 54 mg/day) were equally effective in sustaining retention in treatment, compliance with medication, and counseling regimens. In both groups, 56% of patients remained in treatment through the 16-week flexible dosing period. Overall opioid-positive urine sample rates were 55% and 47% for buprenorphine and methadone groups, respectively; cocaine-positive urine sample rates were 70% and 58%. Evidence was obtained for the effectiveness of dose increases in suppressing opioid, but not cocaine, use among those who received dose increases.
                The results of this study provide further support for the utility of buprenorphine as a new medication in the treatment of opioid dependence and demonstrate efficacy equivalent to that of methadone when used during a clinically guided flexible dosing procedure. Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence. With use of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version ("Berlin Quality of Life Profile") of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p < or = 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p < or = 0.002), muscular tension (p < or = 0.027), general pain (p < or = 0.001), feelings of coldness (p < or = 0.000), heart pounding (p < or = 0.008), runny eyes (p < or = 0.047), and aggressions (p < or = 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buprenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p < or = 0.019), finances (p < or = 0.014), mental health (p < or = 0.010), and overall satisfaction (p < or = 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatment for heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effects on quality of life and physical symptoms. Opioid substitution therapy (OST) in the Ukraine was not provided until 2004. Methadone maintenance therapy only became available in May 2008. Injecting drug users in Ukraine are predominantly injecting self-made opioid solution ('Shirka'). A feasibility study on buprenorphine and methadone maintenance treatment was conducted in 2008.
                A total of 331 opioid dependent patients were given buprenorphine (n=191) or methadone (n=140) as a substitute, and a survey of substance use, HIV transmission risks, and legal and social status was conducted at baseline and at six months follow-up.
                Illegal substance use, illegal activities, incomes and HIV related transmission risks were highly reduced, whereas employment rates and psychiatric problems improved. Retention was comparatively high among the patients in buprenorphine (84.8%) and in methadone maintenance treatment (85.0%) after six months of treatment.
                These data show the successful implementation of OST in the Ukraine among drug users who were predominantly injectors of self-made opioid solutions. Continuing scale-up of OST in the Ukraine is therefore both feasible and highly recommended.
                Copyright 2009 Elsevier B.V. All rights reserved. This study compared the efficacy of buprenorphine to methadone for decreasing cocaine use in patients with combined opioid and cocaine use. Participants (n = 51) were enrolled in a 26-week treatment program and randomly assigned to either buprenorphine or methadone. Dosing was double-blind and double-dummy. Patients were stabilized on either 8 mg sublingual buprenorphine or 50 mg oral methadone, with dose increases given in response to continued illicit cocaine use or opioid use through week 16 of treatment. Maximum doses possible were 16 mg buprenorphine and 90 mg methadone. Average doses achieved were 11.2 mg buprenorphine and 66.6 mg methadone; 49% of the patients received the maximum doses possible. Urine samples were collected three times per week, and there was no significant difference in the rate of cocaine positive urines for the intent-to-treat sample (69% for buprenorphine versus 63% for methadone). For patients who remained in treatment through the flexible dosing period (n = 28), there were significant decreases in cocaine positive urines over time (P < 0.01), but no significant differences between groups or group x time effects. Buprenorphine and methadone were equally effective on measures of treatment retention, urine results for opioids, and compliance with attendance and counseling. These results demonstrate no selective efficacy of either buprenorphine or methadone in attenuating cocaine use in this population, but do provide further support for the equivalent efficacy of buprenorphine and methadone in the treatment of opioid dependence. This randomized clinical trial evaluated the relative efficacy of three buprenorphine dosing schedules. Opioid-dependent adults were randomly assigned to receive buprenorphine seven, 3 or 2 days per week for 24 weeks. Daily maintenance doses were 4, 8, 10, or 12 mg of the sublingual buprenorphine solution. Participants who attended the clinic daily received a maintenance dose of buprenorphine daily. Participants who attended the clinic thrice weekly received double their maintenance dose on Monday and Wednesday, followed by a triple dose on Friday. Participants who attended the clinic twice weekly received quadruple their maintenance dose of buprenorphine on Monday and triple their maintenance dose on Friday. Results demonstrated that all dosing regimens were of comparable efficacy in promoting treatment retention, opioid and cocaine abstinence, and reductions in HIV risk behavior (especially as related to drug use) and severity of life problems. Predictor analyses identified sub-populations of opioid-dependent individuals that may have a more positive treatment outcome under each buprenorphine dosing condition. Less-than-daily dosing schedules may provide the opportunity for treatment programs to serve a greater number of opioid-dependent patients and reduce the risk of medication diversion, which may, in turn, have a positive impact on community support of science-based treatment for opioid-dependence. Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS) To evaluate whether buprenorphine. even without additional control and psychosocial treatment and support, alleviates the problems faced by patients waiting for medication assisted rehabilitation (MAR).
                A randomized, double-blind, 12-week study of Subutex versus placebo without additional support as an interim therapy.
                One hundred and six patients, 70 males and 36 females, waiting for MAR in Oslo. The average age was 38 years with an average history of heroin use of 20 years. Fifty-five patients were assigned to buprenorphine and 51 to a placebo.
                Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday.
                Retention, compliance, self-reported drug-abuse, wellbeing and mental health.
                The average number of days of participation was significantly higher in the buprenorphine group, 42 (median: 29) compared to 14 (median: 11) for the placebo group (P < 0.001). The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group. The buprenorphine group had a larger decrease in reported opioid use (p < 0.001) and in reported use of other drugs, tablets and alcohol abuse (p < 0.01). The group also showed a stronger increase in wellbeing (p < 0.01) and life satisfaction (p < 0.05). None of the participants died.
                The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention, self-reported use of drugs and wellbeing. However, the patients had difficulties in remaining in treatment over time without psychosocial support. This study a) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment. Eighty male and 36 female patients were randomly assigned to daily sublingual buprenorphine (4 or 12 mg) or oral methadone (20 or 65 mg). Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use. Rates of abstinence from illicit opioids were significantly higher for females, within the buprenorphine 4-mg group, females also had significantly better retention, lower rates of opioid-positive urine samples, and higher rates of abstinence from illicit opioids. Lifetime sedative dependence was associated with significantly better retention, decreased rates of cocaine-positive urine samples, and increased rates of cocaine abstinence; among buprenorphine- but not methadone-maintained patients, it was also associated with increased rates of abstinence from illicit opioids. Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence.
                Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance.
                Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study.
                Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome. Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol, cocaine and nicotine dependent populations. The purpose of the present study was to assess the early (1-2 week) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population. The study used a parallel-group design with a behavioral choice component to compare buprenorphine (a mu-opioid partial agonist) to placebo for the treatment of opioid dependence. Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence. Patients were randomly assigned to placebo (n = 60) or 2 mg (n = 60) or 8 mg (n = 30) daily sublingual buprenorphine. All doses were administered double-blind. On days 6-13 all patients could request a dose change, knowing that their new dose would be randomly chosen from the remaining 2 alternatives. Compared to placebo, patients given buprenorphine (independent of dose) showed greater time on initial dose, requested fewer dose changes, used less illicit opioids (assessed by urinalysis), and rated dose adequacy higher. These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence. Buprenorphine may be a useful alternative option to methadone in addicts. Opioids can produce severe changes in the immune system.
                The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance.
                We studied 62 randomized outpatients for a period of 12 months. Subjects (55 males and 7 females; mean age 25+/-4 years; average history of heroin abuse being 2 years) on maintenance treatment were assigned in two groups (A and B). Methadone chloride (medium dose 100 mg/day) was administered to group A, whereas group B received sublingual buprenorphine (32.40+/-2.8 mg/day). Urine toxicological screening, plasma levels of TNF-alpha interleukin-1, interleukin-beta, lymphocyte CD14 and a self-rating depression questionnaire were measured.
                Urine screening was negative for opiates in 17.6% of group A and in 10.7% of group B (p<0.001; r = 0.62). Depression score was 62+/-2 in group A and 55+/-3 in group B (p < 0.01). Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences (p > 0.05) between the two groups.
                The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients. The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin. Furthermore, our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression. The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic. Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.
Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivererd at adequate dosages.