John Grabowski

The impact of impulsivity on cocaine use and retention in treatment.

To determine whether impulsivity was related to severity of drug use and treatment outcome, 50 cocaine dependent subjects underwent baseline measures of severity of current cocaine use and the Barratt Impulsiveness Scale (BIS-11). The hypothesis of the study was that there would be a significant correlation between impulsivity and cocaine use severity. As predicted, there was a significant correlation between BIS-11 total scores and self-reported average daily cocaine use as well as cocaine withdrawal symptoms. A subset of 35 patients underwent a 12-week double-blind placebo controlled trial of buspirone and group therapy. Subjects with high baseline impulsivity remained in the study a significantly shorter period than did subjects with lower baseline impulsivity. This study shows that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment.

Dextroamphetamine for cocaine-dependence treatment : A double-blind randomized clinical trial

A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15-to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulantdependence treatment.

Motivational interviewing with cocaine-dependent patients: A pilot study

A brief motivational interviewing (MI) intervention was evaluated within the context of an outpatient, cocaine-detoxification program. MI was hypothesized to assist patients in completing the detoxification program and to improve outcomes during subsequent treatment. Participants (N = 105) were randomly assigned to MI or to detox-only conditions. Results indicated that although participants completed the detoxification program at equal rates, completers who received MI increased use of behavioral coping strategies and had fewer cocaine-positive urine samples on beginning the primary treatment. MI patients with lower initial motivation were more likely to complete detoxification.

Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: Two placebo-controlled, double-blind trials

Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.

Agonist-Like or Antagonist-Like Treatment for Cocaine Dependence with Methadone for Heroin Dependence: Two Double-Blind Randomized Clinical Trials

Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15–30 or 30–60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.

Diazepam use among methadone maintenance patients: Patterns and dosages

Methadone maintenance patients who use benzodiazepine drugs were interviewed about the dosage levels, patterns, frequency and motives for their use of these drugs. The sample was drawn from two treatment clinics, one in Baltimore (N = 12) and one in Philadelphia (N = 17). Benzodiazepine use was prevalent at both of these clinics - 65 -70% of maintenance patients had positive urinalysis tests during a single month. Ninety-three per cent of survey participants identified diazepam as the drug which they used most often. The median value of the usual daily dose was 40 - 45 mg; 31% reported usual daily doses between 70 and 300 mg and 62% had experience with doses of 100 mg and higher. The majority of the sample reported taking diazepam in a single daily dose within one hour of the time that they ingested their daily methadone; 72% of the sample indicated that diazepam boosts the effects obtained from the daily methadone dose. Another sample of addicts who reported extensive experience with both benzodiazepines and barbiturates indicated that diazepam increases the effects of methadone while barbiturates produce no change in the effects of methadone. Results of this study suggest that patterns and dosages of diazepam use among methadone maintenance patients are primarily abusive rather than therapeutic.

Retention, HIV risk, and illicit drug use during treatment: methadone dose and visit frequency.

OBJECTIVES This study examined two major methadone treatment factors, visit frequency and methadone dose, posited to be important in reducing intravenous drug use and human immunodeficiency virus (HIV) transmission. METHODS One hundred fifty opiate-dependent subjects randomly assigned to four groups received 50 or 80 mg of methadone and attended a clinic 2 or 5 days per week. RESULTS Survival analysis indicated higher dropout rates for groups having five vs two visits per week (Chi2[1]=7.76). Higher proportions of opiate-positive results on urine screens were associated with lower methadone doses (F[1,91]=4.74). CONCLUSIONS Receiving take-home doses early in treatment enhanced treatment retention. The 50-mg dose combined with five visits per week produced the worst outcome. Fewer visits enhanced retention at 50 mg, but opiate use rates were higher at this dose than they were for either 80-mg group. The HIV infection rate at entry was 9%. No subjects seroconverted during the study. Risk behaviors for acquired immunodeficiency syndrome declined over time regardless of group/dose assignment. These results have important implications for modification of regulatory and clinic policy changes.

Naltrexone and relapse prevention treatment for cocaine-dependent patients.

A double-blind, placebo-controlled clinical trial examining the joint action of naltrexone (NTX) in combination with relapse prevention (RP) therapy for the treatment of cocaine dependence was conducted. Eighty-five participants who achieved initial abstinence during the intake evaluation and detoxification phase of the study were randomized into 1 of 4 combined NTX (0 vs. 50 mg) by therapy (RP vs. Drug Counseling) experimental conditions for the 12-week outpatient treatment phase of the study. A random effects regression model to test for group differences on percentage of cocaine-positive urines indicated a significant time by medication by therapy interaction, suggesting less cocaine use over time among subjects receiving RP-50 mg than those in the other conditions. No differences were found for retention or time until first cocaine-positive urine. Naltrexone was well tolerated by participants, with acceptable rates of medication compliance observed. Treatment integrity measures confirmed successful manipulation of the psychotherapy. These results are consistent with the notion that substance use in dependent patients can be reduced with a combination of coping skills training and pharmacologic treatments.

Risperidone for the treatment of cocaine dependence: randomized, double-blind trial.

A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated. Risperidone, a 5-hydroxytryptamine and dopamine D2 antagonist, is an atypical antipsychotic and was a candidate medication for the treatment of cocaine dependence. One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Subjects initially received either placebo or 4 or 8 mg of risperidone, with a subsequent change to active doses of 2 mg and 4 mg. Subjects attended the clinic twice each week, provided urine samples, obtained medication, and underwent one behavioral therapy session per week. The study was terminated at the interim analysis. Retention was worse for the 4- and 8-mg active medication groups. Side effects were primarily associated with the 8-mg dose, although neither 2 mg nor 4 mg was well accepted by subjects. There was no reduction in cocaine use associated with risperidone. The results suggest that although antagonists might be a useful treatment approach, such as in the treatment of opiate dependence, risperidone is unlikely to find broad acceptance with the treatment-seeking population.

Fluoxetine treatment of cocaine-dependent patients with major depressive disorder

Sixty-eight male and female individuals with both DSM-IV diagnoses of cocaine dependence and major depressive disorder were randomly assigned to one of two medication conditions (placebo vs. 40 mg per day) as part of a double-blind, placebo-controlled clinical efficacy trial of fluoxetine for the treatment of this dual diagnosis. During the 12-week outpatient treatment phase all participants also received individual cognitive-behavioral psychotherapy targeting both cocaine use and depression. Depressive symptoms remitted as a function of time in treatment, with no significant medication effects found. Fewer cocaine positive urines were found during the first 6 weeks of treatment in the placebo group compared with the 40-mg group. Cocaine use and depressive symptoms during treatment were significantly correlated. The findings fail to support the role of fluoxetine for treatment of cocaine use and depression in dually-diagnosed patients.