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.

Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine.

In a double-blind, placebo-controlled 12-week randomized clinical trial, we compared amantadine hydrochloride (300 mg/d; n = 33), desipramine hydrochloride (150 mg/d; n = 30), and placebo (n = 31) in the treatment of cocaine-abusing methadone-maintained patients. Treatment retention and medication compliance were excellent, with more than 75% of the patients completing the full 12-week trial. Although reported cocaine abuse was significantly lower in the medicated groups compared with the placebo group at week 4, this difference became nonsignificant at week 8, and no difference was found in cocaine-free urine samples. Future studies of amantadine and desipramine treatment in these patients should consider alternatives to methadone hydrochloride, such as buprenorphine hydrochloride, and the selection of more homogeneous patient subgroups, such as depressed cocaine abusers.

Naltrexone and coping skills therapy for alcohol dependence. A controlled study.

Ninety-seven alcohol-dependent patients were treated for 12 weeks in a double-blind, placebo-controlled study evaluating naltrexone and two manual guided psychotherapies in the treatment of alcohol dependence. Patients were randomized to receive either naltrexone or placebo and either coping skills/relapse prevention therapy or a supportive therapy designed to support the patient's own efforts at abstinence without teaching specific coping skills. Naltrexone proved superior to placebo in measures of drinking and alcohol-related problems, including abstention rates, number of drinking days, relapse, and severity of alcohol-related problems. Medication interacted with the type of psychotherapy received. The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy. For those patients who initiated drinking, however, patients who received naltrexone and coping skills therapy were the least likely to relapse.

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.

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.

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.

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.

Organic affective illness associated with lead intoxication.

Psychiatrists treating patients with depression or nonspecific somatic complaints seldom think of lead intoxication as a possible cause. Because occupational exposure to lead is so common, these disturbances may often be associated with lead intoxication. To facilitate earlier clinical recognition and proper treatment among the many individuals at risk, the authors describe four cases of organic affective disturbance associated with lead intoxication, review the neuropsychiatric disturbances that have been reported with chronic exposure to lead, and report the results of their experience evaluating the psychiatric aspects of lead intoxication among individuals exposed in their work.

Occupation-induced posttraumatic stress disorders.

The authors describe a variant of posttraumatic stress disorder that presents as a somatoform disorder. Applying clearly specified diagnostic criteria, they found that seven of 21 patients who were severely disabled by medically unexplained symptoms following occupational exposure to toxic substances had atypical posttraumatic stress disorder, while three patients had typical posttraumatic stress disorder and the remainder suffered from somatoform disorders. Analysis of these cases revealed specific exposure factors and personality characteristics that favor the development of atypical posttraumatic stress disorder. The authors discuss the theoretical, clinical, and therapeutic advantages of this diagnosis.

Human immunodeficiency virus infection in intravenous drug users: a model for primary care.

PURPOSE: Intravenous drug users (IVDUs) often encounter barriers to primary care. To improve access, we developed a primary care clinic--Central Medical Unit (CMU)--for substance abusers in drug treatment. We report outcomes for services offered to IVDUs with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: During 1990, 24% (120 of 509) of IVDUs eligible for CMU were HIV positive. Diagnostic therapeutic and preventive goals for IVDUs with HIV infection were evaluated for acceptance and compliance by chart review for these 120 patients. RESULTS: On admission, 65% (78 of 120) of patients reported having no source of primary care, 64% (77 of 120) were male, and 77% (92 of 120) were in methadone maintenance. All were screened for tuberculosis, syphilis, and hepatitis; 94% (15 of 16) of eligible patients accepted tuberculosis prophylaxis and 83% (5 of 6) accepted syphilis treatment, but only 36% (5 of 14) accepted hepatitis B vaccine. Of those who accepted therapy, 87% (13 of 15) were compliant with tuberculosis prophylaxis, and 100% (5 of 5) were compliant with syphilis treatment. Influenza vaccine was accepted by 49% (59 of 120) and pneumococcal vaccine by 81% (97 of 120). Ninety-eight percent (118 of 120) accepted T-cell testing: 61% had T-helper counts less than 500/mm3 and 25% were less than 200/mm3. Of those eligible, 89% (70 of 79) accepted antiretroviral therapy, and 100% (35 of 35) accepted Pneumocystis carinii pneumonia prophylaxis. Six-month compliance rates for these therapies were 84% (59 of 70) and 77% (27 of 35), respectively. CONCLUSION: By offering primary care services with drug treatment, the CMU model may be an effective way of providing access to primary care for HIV-infected IVDUs and for facilitating compliance.

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.

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.

Naltrexone, relapse prevention, and supportive therapy with alcoholics: an analysis of patient treatment matching.

Alcohol-dependent patients (N = 97) were randomly assigned to receive either naltrexone or placebo and either relapse prevention therapy or supportive therapy. The present report explored the hypothesis that patients could be matched to the above treatments on the basis of specific pretreatment characteristics. Treatment matching variables explored included craving, alcohol dependence severity, and cognitive measures of learning and memory. Results of linear regression analyses tentatively suggest that patients experiencing higher levels of craving and poorer cognitive functioning may derive the greatest benefit from naltrexone versus placebo. For psychotherapy, lower levels of verbal learning were associated with poorer drinking outcomes for relapse prevention therapy but not for supportive therapy. Conversely, higher levels of verbal learning were associated with better outcomes for relapse prevention therapy but not for supportive therapy.

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.

Matching services to needs. Vocational services for substance abusers.

Problems with employment are common among individuals with substance use disorders, yet comprehensive vocational services are not generally available to them, and vocational interventions are often not matched to their specific needs. This article describes the wide range of vocational problems found among individuals with substance use disorders and the elements of a recently funded vocational program for patients in outpatient and residential drug and alcohol treatment programs. Data are presented describing program activity and documenting program effectiveness for the first 2 years of operation of the program. Three case histories are presented to illustrate the types of services delivered and the matching of services delivered to specific, identified client needs (see Case Histories).

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.

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.

Decline in intravenous drug use among treatment-seeking opiate users.

Opiate users seeking treatment during similar time periods in 1986 (n = 60) and 1988 (n = 82) did not differ significantly with regard to demographic factors, length of addiction, use of cocaine, history of alcohol problems, or indices of depression. In 1988, however, users reported significantly lower rates of current intravenous drug use than was reported in 1986: 39% in 1988, compared to 14% in 1986, reported not currently using IV (chi 2(1, N = 142) = 11.302, p < .001). For the combined periods, current IV users (n = 102) did not differ significantly from those who were not currently using IV (n = 40) with regard to demographic factors, size of habit, history of alcohol problems, or indices of depression. Current IV users had used opiates longer (mean 11.3 years versus 8.4 years; t(1, 65) = 2.20, p < .03), and there was a trend for cocaine use to be associated with current IV administration. For the smaller subset of those who survived waiting lists of between 1 to 4 months from the time of intake to program admission and physical examination (n = 81), 35% (6/17) of those who were not IV drug users at the time of clinic intake reported resuming or initiating IV drug use by the time of program admission. The validity of self-reports of not using IV at the time of program admission was assessed by comparison of self-report with findings of track marks on physical examination: inconsistencies were detected in 11% (1/9) of those whose self-reports indicated no current IV use.

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.