Smoking cessation in methadone maintenance. 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. Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants. Evaluation of an alternative program for MMTP drop-outs: impact on treatment re-entry. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences. One year outcomes for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS). Promoting abstinence from cocaine and heroin with a methadone dose increase and a novel contingency. Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study.
To evaluate relapse prevention (relapse prevention) and contingency management (contingency management) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers.
                Experimental, 2 (relapse prevention)x2 (contingency management) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period, followed by randomization to 12 weeks of treatment, and 6- and 12-month follow-up visits.
                Three narcotic treatment centers in Los Angeles.
                One hundred and seventy-five participants who met all inclusion and no exclusion criteria.
                Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions: patch-only, relapse prevention + patch, contingency management + patch and relapse prevention + contingency management + patch.
                Thrice weekly samples of breath (analyzed for carbon monoxide) and urine (analyzed for metabolites of opiates and cocaine) and weekly self-reported numbers of cigarettes smoked.
                Participants (73.1%) completed 12 weeks of treatment. During treatment, those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies (F3,4680=6.3, P=0.0003), with no similar effect observed for relapse prevention. At follow-up evaluations, there were no significant differences between conditions. Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria (F1,2054=14.38, P=0.0002; F1,2419=16.52, P<0.0001).
                Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence, although long-term effects are not generally maintained. Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment. 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. 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. Retention in a Methadone Maintenance Treatment Program (MMTP) is predictive of abstaining from heroin and has other benefits. Many individuals leave treatment before they experience these positive outcomes.
                This research project targeted MMTP drop-outs with an intervention designed to assist them in returning to drug treatment.
                Subjects who had left MMTP within the prior 12 months were randomly assigned to intervention or comparison groups. The 3-month long intervention consisted of street outreach, cognitive behavioral groups, and individual counseling. Data were analyzed for 175 subjects who were out of treatment at baseline and who returned for a 6-month follow-up interview (Intervention group, N=111; Comparison group, N=64).
                A total of 87% of subjects assigned to the intervention condition participated in at least one component. Intervention subjects who attended two or more cognitive behavioral group sessions were more likely than those who attended 0-1 sessions or those in the comparison group to have returned to treatment during the 6 month follow up time period (72 vs. 53 vs. 50%, respectively, P<0.05, chi square test).
                MMTP drop-outs need not be lost to the drug treatment system if special efforts are made to engage them in interventions developed to encourage treatment re-entry. 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. The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p < 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p < 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA. To determine 1 year outcomes for drug use, criminality, psychopathology and injection-related health problems in those entering treatment for heroin dependence in Australia.
                Longitudinal prospective cohort study.
                Seven hundred and forty five individuals entering treatment (methadone/buprenorphine maintenance therapy; detoxification; residential rehabilitation) and 80 heroin users not seeking treatment.
                Sydney, Melbourne and Adelaide, Australia.
                A total of 657 individuals were re-interviewed at 1 year, 80% of the original sample. There were substantial reductions in heroin and other drug use across all three treatment modalities. The majority of those who had entered treatment were heroin abstinent at 1 year (maintenance therapy 65%, detoxification 52%, residential rehabilitation 63%) compared to 25% of the non-treatment sample. The reduction in heroin use among the treatment samples was paralleled by reductions in poly drug use. There were also substantial reductions in risk-taking, crime and injection-related health problems across all treatment groups, and less marked reductions among the non-treatment group. Psychopathology was dramatically reduced among the treatment modalities, while remaining stable among the non-treatment group. Positive outcomes at 1 year were associated with a greater number of cumulative treatment days experienced over the 1 year follow-up period ('treatment dose') and fewer treatment episodes undertaken in that time ('treatment stability').
                At 1 year, there were impressive reductions in drug use, criminality, psychopathology and injection-related health problems following treatment exposure. The positive findings were associated with a greater "dose" of treatment, and with more treatment stability over the follow-up period. To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 x 3 (dosexcontingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100mg/day, double-blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or "split"). The "split" contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was "split" between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required. Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospective study. Primary outcomes were patient preference for opioid and pain control while physical, cognitive and role functioning were secondary outcomes. The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period. During switching and a one-week dose titration period, patients were given additional methadone if required. During dose titration one patient experienced sedation requiring naloxone. Four patients were switched back to morphine due to poor pain control, drowsiness or sweating. Seven patients preferred long-term (>nine months) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved. This study brings novel information on the long-term consequences for pain control, health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain.
Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long-
acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.