Juliana Pakes

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.

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.

TREATMENT OF HEROIN DEPENDENCE WITH BUPRENORPHINE IN PRIMARY CARE

Buprenorphine is an effective treatment for heroin dependence. The feasibility and potential efficacy of buprenorphine with brief counseling in primary care is unknown. We enrolled 14 heroin dependent patients in a 13-week clinical trial using thrice weekly buprenorphine along with brief counseling in the primary care center of an urban medical center. Primary outcomes included urine toxicology and treatment retention. Opioid-positive urine toxicology tests reduced over the 13-week period from 95 to 25% (p<0.05). Eleven patients (79%) had greater than or equal to one week of opioid-free urine toxicologies. Nine patients (64%) had greater than or equal to three weeks of opioid-free urine toxicologies. Eleven patients (79%) were retained through the maintenance phase. We conclude that buprenorphine maintenance is feasible in a primary care setting.

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.

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.

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.

Linking Process and Outcome in the Community Reinforcement Approach for Treating Cocaine Dependence: A Preliminary Report

This preliminary study evaluated the relationship between therapy process variables (mechanistic processes and interpersonal processes), and treatment outcome (i.e., retention and cocaine abstinence) among 16 cocaine‐dependent pregnant or postpartum women treated with the Community Reinforcement Approach (CRA). Two new rating scales were developed for this purpose. The Mechanisms of Action Rating Scale (MARS) assesses five CRA mechanistic domains (Big Picture goals, functional analyses of behavior, nondrug‐related activities, skills training, and homework). The Interpersonal Variables Rating Scale (IVRS) measures three nonspecific or interpersonal dimensions of psychotherapy (i.e., empathy, response to resistance, and therapeutic alliance). These rating scales were used to rate one, early treatment, videotaped CRA session for each subject. Results indicated that: 1) sessions with patients who achieved three or more consecutive weeks of cocaine abstinence were rated significantly higher on therapist empathy and positive responses to resistance, and total IVRS scores (all of which indicate positive interpersonal processes); and 2) Big Picture goals, positive therapeutic alliance, and total IVRS scores were significantly and positively correlated with number of consecutive weeks of cocaine‐negative urine toxicology tests. Only MARS homework scores were significantly and positively associated with number of study weeks completed. Finally, the pattern of interrelationships among the MARS subdomains suggests the coherence of the multifaceted CRA treatment. The findings of this preliminary study suggest the importance of monitoring both mechanistic and interpersonal processes during CRA treatment of cocaine dependence.

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 Mothers 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.

Voucher Purchases in Contingency Management Interventions for Women with Cocaine Dependence

ObjectiveVoucher-based Contingency Management (CM) has been shown to be effective in treating cocaine dependence, but the relative impact of extensive voucher purchase guidelines has not been evaluated. Consequently, our objective was to investigate the effect of purchase guidelines on voucher purchases. MethodsWe evaluated voucher purchases made by 94 cocaine dependent women who were enrolled in a randomized clinical trial of the Community Reinforcement Approach (CRA) versus Twelve-Step Facilitation (TSF), where extensive purchase guidelines were only part of CRA. ResultsIn CRA, 70% of the purchases were consistent with the guidelines offered. The most frequent purchases were for social/recreational activities (30%), the participants child (non-basic needs; 17%), and household items (15%). There were no significant differences in percentages of purchases between CRA and TSF. Additionally, preliminary findings on the relationship between voucher purchase patterns and cocaine abstinence are presented. ConclusionThe findings suggest that extensive purchase guidelines may not be a critical aspect of voucher reward programs.