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.

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.

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.

Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cocaine-abusing parturients undergoing cesarean section. A cohort study.

BACKGROUND: Cocaine use in the United States is prevalent among pregnant women from inner city neighborhoods. To determine the anesthetic implications of cocaine use in parturients undergoing cesarean section delivery, the authors conducted a cohort study. METHODS: One thousand nine hundred seven women presenting for prenatal care were interviewed regarding substance abuse. Urine was analyzed for benzoylecgonine, tetrahydracannabinol, benzodiazepines, and opioids. Next all parturients who underwent cesarean section delivery were identified and their records reviewed for anesthetic and obstetric outcomes. RESULTS: Among the 51 women who were classified as cocaine abusers, the most frequent reasons for cesarean section were fetal distress (48%) and abruptio placenta (21%). In a multivariate model, cocaine abuse before delivery was shown to be an independent predictor of preoperative diastolic hypertension (F = 10.6, P = 0.01). Similarly, univariate analysis showed that immediately after intubation, diastolic blood pressure was significantly higher among parturients who used cocaine (99 +/- 13 mmHg v. 87 +/- 18 mmHg; P = 0.02). In contrast, epidural anesthesia was associated with hypotension significantly more often among cocaine-abusing parturients (44% vs. 10%; P = 0.04). A higher rate of perioperative wheezing was reported among patients who abused cocaine (16% vs. 6%; relative risk = 2.7); this finding, however, did not persist in multivariate analysis. Operative blood loss was similar in all groups (P = NS), and no ventricular dysrhythmias or cerebrovascular or coronary ischemic episodes were reported in any of the parturients. CONCLUSIONS: Although cocaine-abusing parturients are at higher risk for interim peripartum events such as hypertension, hypotension, and wheezing episodes, there is no significant increase in rates of maternal morbidity or death.

Thrombocytopenia in pregnant women who use cocaine.

OBJECTIVE: Our purpose was to determine the prevalence of cocaine-associated thrombocytopenia. STUDY DESIGN: This cohort study was conducted in an inner-city prenatal center. A total of 1907 patients were screened by the Mother's Project, which is an intervention project for inner-city cocaine-abusing parturients. Platelet counts were grouped by illicit drug usage. RESULTS: Platelet counts were available in 37% (709) of subjects; there were no differences between subjects with available platelet counts and those without on illicit drug use or other demographic measures. Five groups were defined: drug-free group (n = 331), cocaine group (n = 104), cocaine and opiates group (n = 11), opiates group (n = 18), and other-drug group (n = 236). Nineteen subjects had a low platelet count (< 150 x 10(9)/L). The medical records of all subjects with a low platelet count were reviewed for any medical condition known to be associated with thrombocytopenia, and two subjects were excluded. The rate of thrombocytopenia in the drug-free group was 1.5%, whereas the rate in the cocaine group was 6.7% (relative risk 4.4, p < 0.05). Because of the reported association of thrombocytopenia with seropositive human immunodeficiency virus status, seropositive women were excluded from the analysis. Even after human immunodeficiency virus status adjustments for the estimated rate, the cocaine-using group continued to have a significantly higher rate of thrombocytopenia (5.4% to 7.2% vs 1.23% to 1.26%, p < 0.05 to p < 0.005). CONCLUSIONS: These results indicate that cocaine use is an independent risk factor for thrombocytopenia in an inner-city parturient population.

Buprenorphine: dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans.

Fifteen subjects dependent on both opioids and cocaine completed an ascending and tapering schedule of buprenorphine dosing, with maintenance for 21 days at each dose of buprenorphine (4, 8, 12, 16 mg sublingual daily) during both ascending and tapering phases. Higher doses of buprenorphine led to greater reductions in opioid use: 64.7% of subjects were opioid abstinent for 3 weeks at the 16-mg dose compared to 27.3% at the 4-mg ascending dose. The proportion of cocaine-positive urine toxicologies was significantly lower during buprenorphine tapering (12 mg, 8 mg, 4 mg) compared to ascending doses up to 8 mg, with intermediate results at 12 mg and 16 mg during the ascending phase (F value = 6.6, df = 8,813, p < 0.001). Self-reported days, times, and quantity of cocaine used per week showed a similar pattern of intermediate reductions at the 12-mg and 16-mg dose during the ascending phase and significantly reduced values during the descending schedule. There were no significant buprenorphine dose effects on cocaine euphoria. This study indicates that buprenorphine dose has a significant and substantial impact on opioid use and a significant but less robust impact on cocaine use, with higher doses and longer time on buprenorphine leading to attenuated cocaine use.

Personality dysfunction in depressed adolescents.

The personality characteristics of 35 consecutively assessed adolescents who met the DSM-III criteria for a current depressive disorder were assessed using independent structured interviews and paper and pencil measures. Sixty-five percent of the sample met the criteria for an Axis II personality disorder. The single most common diagnosis was borderline personality disorder (30%). Depressed adolescents with a concurrent personality disorder were less self-confident, displayed more neuroticism, and were emotionally reliant on others. They also demonstrated greater cognitive distortion. Teenagers who present with a depressive disorder warrant a comprehensive personality assessment. The combination of affective and personality disorder in such patients is associated with attitudes and interpersonal problems which should be therapeutically addressed in addition to symptomatic treatment of the depressed mood. Clinicians should be aware that depressed adolescents with personality disorder may be more likely to make a suicide attempt.