Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programs. Outcomes after methadone maintenance and methadone reduction treatments: two-year follow-up results from the National Treatment Outcome Research Study. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. Predictors of patient retention in a newly established methadone maintenance treatment programme. Prognostic factors in Buprenorphine- versus methadone-maintained patients. Correlates of retention on the South Australian Methadone Program 1981-91. Retention in methadone maintenance and heroin addicts' risk of death. Physicians' attitudes and retention of patients in their methadone maintenance programs. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Correction of error: Methadone dosage and retention of patients in maintenance treatment. Retention in a low-threshold methadone maintenance program. Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance. Proceedings: Efficacy and side effects of three widely different methadone doses. Methadyl acetate and methadone as maintenance treatments for heroin addicts. A veterans administration cooperative study. Dose-response effects of methadone in the treatment of opioid dependence. The relationship of methadone dose and other variables to outcomes of methadone maintenance. A controlled trial of buprenorphine treatment for opioid dependence. Methadone dosage, cocaine and opiate abuse. Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage.
The present study evaluates the effectiveness of low-threshold methadone maintenance in reducing overdose mortality. In a prospective cohort study conducted in Amsterdam, 498 Dutch injecting drug users (IDU) provided 1,969 person years of follow-up (1989-1995). Forty-four IDU died in this period, 15 due to illicit drug overdose. Compared to IDU not in maintenance, the adjusted relative risk for overdose mortality among those receiving 5-50 mg, 55-70 mg, and 75+ mg were 0.35, 0.13, and 0.11, respectively (p < .05). Also current injection use and HIV-seropositivity were independent predictors for overdose mortality. Whereas previous studies indicated effectiveness of methadone-assisted detoxification and high-dose maintenance programs in reducing mortality, the present study findings suggest that low-threshold maintenance programs also reduce overdose mortality, with higher dosages being most protective. This paper provides a detailed analysis of the 2-year outcomes for 351 drug misusers allocated on an intention-to-treat basis to methadone maintenance or methadone reduction treatments. Both groups showed substantial reductions in their use of illicit drugs and in other outcome areas. However, whereas most methadone maintenance patients received maintenance, only about one third of those allocated to methadone reduction received methadone reduction, and many actually received a form of methadone maintenance. Reduction patients were more likely to receive low doses of methadone, and were less likely to remain in treatment. For maintenance patients, higher doses and retention in treatment were both associated with improvements in illicit heroin use at 2 years. For the reduction patients, the more rapidly the methadone was reduced, the worse the heroin use outcomes. For patients in both treatment conditions, reductions in heroin use were associated with improvements in other outcome areas. The more severely dependent patients showed better outcomes in methadone maintenance. Methadone reduction treatment processes were associated with poor outcomes, and many patients who were allocated to methadone reduction treatment did not receive reduction treatment as intended. This calls into question the appropriateness of either the initial treatment planning process or the treatment delivery process, or both. A clearer distinction should be made between methadone maintenance and methadone reduction. Treatment goals should be made explicit both to the patient and to the clinical staff at the start of treatment. We suggest the need for a reappraisal of the goals and procedures of methadone reduction treatment. Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted.
                To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence.
                A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995.
                Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md.
                One hundred ninety-two eligible clinic patients.
                Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling.
                Opioid-positive urinalysis results and retention in treatment.
                By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification.
                Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use. 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. 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. To investigate correlates of retention on the South Australian Methadone Program during 1981-91.
                Retrospective study of a nonstratified random sample of 229 HIV-negative clients who received methadone between January 1981 and June 1991. Data were collected from clinical records of the 229 HIV-negative clients and also from the 40 clients known to be infected with HIV during the decade.
                Being HIV positive, receiving larger maximum doses of methadone, receiving methadone from a private pharmacy and enrolling later in the decade were all associated with longer retention times on the program.
                This study supports the findings of previous studies, that maximum dose of methadone is crucial to retention in methadone programs, But even allowing for maximum dose, obtaining methadone from a private pharmacy was also strongly associated with retention on the program. The more 'humane' clinic policy later in the decade is likely to have increased retention and reduced illicit drug use also. A long-term follow-up was made of a cohort of 307 heroin addicts admitted into a high-dose, Australian methadone maintenance programme in the early 1970s. Using data from clinic records, official death records and methadone treatment histories, it was found that subjects were nearly three times as likely to die outside of methadone maintenance as in it (95% CI RR 1.45 to 5.61). Data were further analyzed using Cox regression to investigate the association of maximum daily methadone dose and a change in clinic policy with retention in maintenance treatment. It is estimated that subjects given a maximum daily dose of 80 mg were nearly twice as likely to be discharged during the first three years of maintenance as those given 120 mg (95% CI RR 1.3 to 2.2). The estimated median time in maintenance for subjects given a maximum dose of 120 mg was 1150 days while for 80 mg it was 660 days. It is further estimated that the change in clinic policy from abstinence to indefinite maintenance reduced to one-third subjects' risk of leaving after three years' of treatment (95% CI RR 0.19 to 0.54). It is concluded that, in order to minimize heroin addicts' risk of death, they should be offered indefinite, high-dose methadone maintenance. A study was undertaken to investigate the influence of methadone prescribers' commitment to abstinence-oriented policies on retention in their maintenance programs. Two hundred and eighty patients recently enrolled in single-person, private methadone programs were interviewed and followed for 8 years. The prescribing physicians' scores on an Abstinence Orientation Scale, derived from an independent sample of methadone program staff, were significantly associated with their patients' risk of premature discharge. The influence of program orientation on retention was greater the higher the maximum dose of methadone. More attention should be paid to the effect of staff attitudes and beliefs on the effectiveness of maintenance treatment. 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. nan 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. Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions.
                Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis).
                Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving.
                In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits. nan This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals. The starting sample consisted of 146 patients receiving low-dose methadone, 142 patients receiving methadyl acetate. Patients were first given 30 mg of both drugs, and doses were incremented by 10 mg/week until they stabilized at methadyl acetate, 80 mg three times a week, and methadone hydrochloride, 50 mg daily or 100 mg daily. Dosage was fixed for the balance of the 40-week treatment period. Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study. Relative efficacy was evaluated by illicit drug use, program retention and attendance, and global staff judgments. It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methoadone in terms of efficacy. Both methyadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study. To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue.
                A randomized, double-blind, placebo-controlled study.
                A methadone treatment research clinic.
                Participants (n = 247) were opioid-dependent patients with a high rate of cocaine use.
                All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day. Individual counseling and group therapy were included.
                Treatment retention and illicit drug use as determined by intensive urine monitoring.
                Retention was better for patients who remained on active medication. By treatment week 20, retention was 52.4% for the 50-mg, 41.5% for the 20-mg, and 21.0% for the 0-mg group (50 versus 0 and 20 versus 0, P < 0.05; 50 versus 20, P > 0.05). Only the 50-mg treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg and 0-mg groups, respectively; P < 0.05) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20- and 0-mg groups, respectively; P < 0.05).
                There is a dose-response effect for methadone treatment. Doses as low as 20 mg may improve retention but are inadequate for suppressing illicit drug use. The authors evaluated the relationship of methadone dose to retention in treatment and to urine tests for morphine and cocaine in a cohort of 610 opioid users admitted to methadone maintenance and followed for 1 year. Methadone dosing was flexible, with patient participation in dose decisions. The maximum dose during treatment ranged from 10 mg to 110 mg, with a mean of 52 mg. Higher doses were associated with increased retention through the dose range of 60 mg-69 mg. Dose was not related to the likelihood of a positive morphine test but was related to the likelihood of a positive cocaine test. In this study, with flexible dosing and patient participation in dose decisions, patients were retained on methadone about as well as was reported in a previous study with patients on a fixed dose of 80 mg. 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. nan Retention in treatment among 1503 heroin users attending public treatment centres in 1995 was studied. Three different treatments were considered: methadone maintenance, drug-free program and naltrexone. The retention rate after 1 year was 40% for patients in methadone maintenance, 18% in naltrexone and 15% in drug-free program. For patients in maintenance, methadone dosage and clinic policy were the most important factors for retention. Patients taking > or = 60 mg/day and 30-59 mg/day were respectively 70 and 50% more likely to remain in treatment than those receiving a < 30 mg daily dose. Patients in maintenance-oriented clinics were 30% more likely to remain in treatment than those in abstinence-oriented centres.