Buprenorphine/naloxone treatment practices in Malaysia: Results of national surveys of physicians and patients.

OBJECTIVE: Medication assisted treatment with buprenorphine/naloxone (Bup/Nx), including prescribing and dispensing practices of general practitioners (GPs) in Malaysia and their patients' experiences with this treatment have not been systematically examined. The current study surveyed GPs providing Bup/Nx treatment and patients receiving office-based Bup/Nx treatment in Malaysia. METHODS: Two cross-sectional surveys of GPs (N=115) providing outpatient Bup/Nx maintenance treatment and of patients (N=253) currently receiving Bup/Nx treatment throughout peninsular Malaysia. RESULTS: Physicians prescribed Bup/Nx dosages in the range of 2-4mg daily for 70% of patients and conducted urine testing in the past month on approximately 16% of their patients. In the patient survey, 79% reported taking daily Bup/Nx doses of 2mg or less; 82% reported that no urine toxicology testing had been conducted on them in the past month, 36% had an opiate positive urine test at the time of the survey, 43% reported illicit opiate use, 15% reported injection of heroin and 22% reported injection of Bup/Nx in the past month. CONCLUSION: Low daily Bup/Nx doses, lack of behavioral monitoring or counseling, and high rates of continued drug use, including injection of drugs and medications during Bup/Nx treatment in Malaysia, indicate continuing problems with implementation and less than optimal treatment effectiveness. High cost of Bup/Nx in Malaysia may deter patients from seeking treatment and contribute to taking low Bup/Nx dosages. Improved training of physicians and establishing standards for Bup/Nx dosing, routine toxicology testing, and counseling may be needed to improve care and treatment response.

Impulsivity, cognitive function, and their relationship in heroin-dependent individuals.

There is mixed evidence concerning cognitive function and heroin dependence. In this study, abstinent heroin-dependent individuals (n = 86) and age- and sex-matched non-drug-using controls (n = 88) were compared on self-report measures of impulsivity and computerized assessments of cognitive function. Abstinent heroin-dependent individuals reported greater motor impulsivity and experience seeking and showed functional weaknesses in cognitive ability, including impulsivity and distractibility (d = 0.28 to 0.49), but not decision making or working memory. Self-reported impulsivity was uncorrelated with cognitive function. These results suggest underlying brain-related factors in heroin dependence and have implications for therapeutic intervention.

Behavioral drug and HIV risk reduction counseling (BDRC) in MMT programs in Wuhan, China: a pilot randomized clinical trial.

This pilot clinical trial evaluated whether the efficacy of methadone maintenance treatment (MMT) provided with limited psychosocial services is improved by the addition of manual-guided behavioral drug and HIV risk reduction counseling (BDRC). Heroin dependent individuals (n=37) enrolling in two MMT clinics in Wuhan, China, received standard MMT services, consisting of daily medication at the clinics and infrequent additional services on demand, and were randomly assigned to MMT only (n=17) or MMT with weekly individual BDRC (n=20) for 3 months. Participants were followed for six months from the time of enrollment (3 months active counseling phase and 3 months follow-up while treated with standard MMT). Primary outcome measures included reductions of HIV risk behaviors and illicit opiate use and treatment retention. Participants were 81% male; mean (SD) age 36.7 (7.2) years; there were no significant baseline differences between the two groups. Participants in MMT+BDRC achieved both greater reductions of HIV risk behaviors (p<0.01), as indicated by the scores on a short version of the AIDS Risk Inventory, and of illicit opiate use, as indicated by the proportions of opiate negative test results during the active phase of the study and the follow-up (p<0.001). 83.3% in the MMT+BDRC group and 76.2% in the standard MMT group were still actively participating in MMT at 6 months. Manual-guided behavioral drug and HIV risk reduction counseling is feasible to deliver by the trained MMT nursing personnel and appears to be a promising approach for improving the efficacy of standard MMT services in China.

Injection of buprenorphine and buprenorphine/naloxone tablets in Malaysia.

BACKGROUND: Buprenorphine maintenance is efficacious for treating opioid dependence, but problems with diversion and misuse of buprenorphine (BUP) may limit its acceptability and dissemination. The buprenorphine/naloxone combination tablet (BNX) was developed to reduce potential problems with diversion and abuse. This paper provides data regarding the characteristics of BUP injection drug users in Malaysia and preliminary data regarding the impact of withdrawing BUP and introducing BNX. BUP was introduced in 2002 and subsequently withdrawn from the Malaysian market in 2006. BNX was introduced in 2007. METHODS: A two wave survey of BUP IDUs was conducted shortly prior to BUP withdrawal from the Malaysian market (n=276) and six months after BNX was introduced (n=204). Six focus groups with BUP and/or BNX IDUs were also conducted shortly before the second wave. RESULTS: In addition to current BUP or BNX IDU, 96% of first wave participants and 97% second wave participants reported lifetime heroin IDU preceding the onset of their BUP/BNX IDU. Additionally, 58% of first and 64% of second wave survey participants reported current heroin IDU. Benzodiazepine abuse, often injected with BUP, was reported in both the surveys. Focus group participants reported that BNX was not as desirable as BUP, nonetheless, the results of the second wave survey suggest a continuing widespread BNX IDU, at least in Kuala Lumpur. CONCLUSIONS: In Malaysia, BUP and BNX IDU occur among heroin IDUs. The introduction of BNX and withdrawal of BUP may have helped to reduce, but did not eliminate the problems with diversion and abuse.

Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial.

This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight.

Methadone maintenance in primary care: a randomized controlled trial.

CONTEXT: Methadone maintenance is an effective treatment for opioid dependence, yet its use is restricted to federally licensed narcotic treatment programs (NTPs). Office-based care of stabilized methadone maintenance patients is a promising alternative but no data are available from controlled trials regarding this type of program. OBJECTIVE: To determine the feasibility and efficacy of office-based methadone maintenance by primary care physicians vs in an NTP for stable opioid-dependent patients. DESIGN: Six-month, randomized controlled open clinical trial conducted February 1999-March 2000. SETTING: Offices of 6 primary care internists and an NTP. PATIENTS: Forty-seven opioid-dependent patients who had been receiving methadone maintenance therapy in an NTP without evidence of illicit drug use for 1 year and without significant untreated psychiatric comorbidity were randomized; 1 patient refused to participate after treatment assignment to NTP. INTERVENTIONS: Patients were randomly assigned to receive office-based methadone maintenance from primary care physicians, who received specialized training in the care of opioid-dependent patients (n = 22), or usual care at an NTP (n = 24). MAIN OUTCOME MEASURES: Illicit drug use, clinical instability (persistent drug use), patient and clinician satisfaction, functional status, and use of health, legal, and social services, compared between the 2 groups. RESULTS: Eleven of 22 (50%; 95% confidence interval [CI], 29%-71%) patients in office-based care compared with 9 of 24 (38%; 95% CI, 21%-57%) of NTP patients had a self-report or urine toxicology test result indicating illicit opiate use (P =.39). Hair toxicology testing detected an additional 2 patients in each treatment group with evidence of illicit drug use, but this did not change the overall findings. Ongoing illicit drug use meeting criteria for clinical instability occurred in 4 of 22 (18%; 95% CI, 7%-39%) patients in office-based care compared with 5 of 24 (21%; 95% CI, 9%-41%) NTP patients (P =.82). Sixteen of the 22 (73%; 95% CI, 54%-92%) office-based patients compared with 3 of the 24 (13%; 95% CI, 0%-26%) NTP patients thought the quality of care was excellent (P =.001). There were no differences over time within or between groups in functional status or use of health, legal, or social services. CONCLUSIONS: Our results support the feasibility and efficacy of transferring stable opioid-dependent patients receiving methadone maintenance to primary care physicians' offices for continuing treatment and suggest guidelines for identifying patients and clinical monitoring.

Thrice-weekly versus daily buprenorphine maintenance.

BACKGROUND: Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. METHODS: After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use. RESULTS: There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%). CONCLUSIONS: At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial.

BACKGROUND: We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects. METHODS: Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks. RESULTS: Groups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo. CONCLUSIONS: This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

Community reinforcement approach for combined opioid and cocaine dependence. Patterns of engagement in alternate activities.

We compared outcomes for agonist-maintained patients with combined opioid and cocaine dependence who were treated in an earlier clinical trial with group drug counseling (DC; n = 57) or in a current trial with the Community Reinforcement Approach (CRA; n = 60). The association between engagement in nondrug-related activities and abstinence was also evaluated. There were no significant differences between the treatments in retention or drug use. The total number of hours and average hours per week engaged in nondrug-related activities was significantly higher for CRA-treated patients who achieved abstinence from opioids, cocaine, or both combined than for those who never achieved abstinence. Although CRA was not more effective overall than DC, the finding that engagement in reinforcing community activities unrelated to drug use (e.g., planned pleasurable events or parenting activities) was associated with abstinence suggests that the planning and reinforcement of specific nondrug-related social, vocational, and recreational activities is a crucial component of CRA.

Plasma concentrations of buprenorphine 24 to 72 hours after dosing.

BACKGROUND: This study evaluated plasma buprenorphine concentrations 24-72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg/70 kg to 44 mg/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms. METHODS: Opiate dependent subjects (n = 10) were maintained in an outpatient clinic for two 3-week periods at each of three thrice-weekly buprenorphine dose schedules (providing a weekly total buprenorphine dose of 64, 84 and 112 mg) and for 1 week of a daily buprenorphine dose of 16 mg/70 kg. Plasma samples were obtained 24, 48 and 72 h following administration of buprenorphine. Urine samples were also collected and opiate withdrawal symptoms, agonist effects and the use of heroin, cocaine, alcohol and other drugs, were assessed. RESULTS: Plasma levels showed a wide range of intra- and inter-subject variability. Nonetheless, higher doses of buprenorphine resulted in higher plasma concentrations at each time point and plasma concentration decreased with time. There were no significant differences in heroin use across dosing. Rates of withdrawal symptoms were low and did not differ across dosing schedules. CONCLUSIONS: In the two highest dose schedules, plasma levels 72 h following the administration of the highest dose and at 48 h after the lower dose, were comparable to plasma concentrations at 24 h following daily administration of 16 mg/70 kg of buprenorphine.

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. RESULTS: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. CONCLUSIONS: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Assessment of HIV risk.

Based on the review of existing instruments and analysis of problems encountered in clinical and research practice with one of the most commonly used assessment instruments, the RAB, this paper proposes a number of solutions aimed at improving validity, and efficiency of assessment of HIV risk in drug abusing populations. Briefly, five domains of assessment are discussed: intravenous drug use, high-risk sexual behaviors, knowledge of HIV transmission and methods of prevention, psychological aspects of behavioral change, and epidemiological factors of HIV transmission. The paper discusses also changes in format, scope, and context, as well as scoring procedures that may improve discriminability and sensitivity to detect change of a comprehensive HIV risk assessment instrument. Finally, a process of developing an HIV risk assessment instrument, the ARI-I, which is based on the proposed recommendations and which incorporates methodological improvements discussed in the paper is briefly described.

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic.

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use. SUBJECTS AND METHODS: Opioid-dependent patients were randomly assigned to receive thrice weekly buprenorphine maintenance in a primary care clinic that was affiliated with a drug treatment program (n = 23) or in a traditional drug treatment program (n = 23) in a 12-week clinical trial. Primary outcomes were retention in treatment and urine toxicology for opioids; secondary outcomes were opioid withdrawal symptoms and toxicology for cocaine. RESULTS: Retention during the 12-week study was higher in the primary care setting (78%, 18 of 23) than in the drug treatment setting (52%, 12 of 23; P = 0.06). Patients admitted to primary care had lower rates of opioid use based on overall urine toxicology (63% versus 85%, P < 0.01) and were more likely to achieve 3 or more consecutive weeks of abstinence (43% versus 13%, P = 0.02). Cocaine use was similar in both settings. CONCLUSIONS: Buprenorphine maintenance is an effective treatment for heroin dependence in a primary care setting.

Types of abuse and cocaine use in pregnant women.

Previous research has found an association between childhood and adult physical and sexual abuse and substance abuse, but has not examined or compared specific dimensions of the abuse experience, such as its age of onset or the type, severity, or frequency. Women receiving perinatal care (N = 1189) at an inner-city hospital clinic were systematically questioned about their lifetime and current cocaine use and experiences of abuse. We found an association between a history of abuse in childhood and lifetime and current cocaine use, as well as physical and sexual abuse during childhood and pregnancy. There was no difference in the rates of cocaine use between women whose onset of abuse was in childhood versus adulthood. Childhood sexual abuse (alone or in combination with physical abuse) was more associated with lifetime cocaine use than was physical abuse alone. Cocaine use was related to the severity, but not the frequency of abuse.

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally cocaine-exposed children are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Furthermore, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly when such children are also exposed to the chaotic environmental conditions often characterizing substance-abusing families.

Prognostic factors in Buprenorphine- versus methadone-maintained patients.

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.

When is less treatment better? The role of social anxiety in matching methadone patients to psychosocial treatments.

In response to a need to match drug users to the most appropriate and cost-effective level of care, it was hypothesized the socially anxious methadone-maintained patients would attain greater benefit from coping skills training provided in the context of a low-intensity enhanced standard methadone maintenance intervention (E-STD) than in the context of a high-intensity, socially demanding day treatment program (DTP). Social anxiety was assessed in 307 methadone-maintained patients using the Social Anxiety and Distress Scale prior to randomization to either E-STD or DTP. The hypothesis was supported: Socially anxious patients were drug free longer during treatment, were more likely to be abstinent at treatment completion, and had greater reductions in HIV risk behaviors if assigned to the lower intensity intervention, which was provided at 1/3 the cost of the DTP.

Three methods of opioid detoxification in a primary care setting. A randomized trial.

BACKGROUND: Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients. OBJECTIVE: To compare three pharmacologic protocols for opioid detoxification in a primary care setting. DESIGN: Randomized, double-blind clinical trial with random assignment to treatment protocols. SETTING: A free-standing primary care clinic affiliated with drug treatment programs. PATIENTS: 162 heroin-dependent patients. INTERVENTIONS: Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine. MEASUREMENTS: Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms. RESULTS: Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone. CONCLUSIONS: Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.