Replacement medication for cocaine dependence: methylphenidate. Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence. Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Effects of oral methamphetamine on cocaine use: a randomized, double-blind, placebo-controlled trial. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial. Mazindol treatment for cocaine dependence. A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Mazindol for relapse prevention to cocaine abuse in methadone-maintained patients. Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Bupropion hydrochloride versus placebo, in combination with cognitive behavioral therapy, for the treatment of cocaine abuse/dependence.
Agonists, or "replacement medications," are useful adjuncts in treatment of opiate and nicotine dependence. They have not been systematically examined in cocaine dependence. Results of early open trials with methylphenidate for treatment of cocaine dependence were equivocal. Twenty-four cocaine-dependent subjects were enrolled in an 11-week double-blind, placebo-controlled study of methylphenidate. Assignment was random. Intake included a 2-day human laboratory procedure in which subjects received initial doses of methylphenidate or placebo. Subjects attended the clinic Monday through Friday and received oral doses of methylphenidate (5 mg plus 20-mg sustained release) or placebo at 8:00 a.m., with afternoon and weekend take-home doses (20 mg sustained-release or placebo) provided in Medication Events Monitoring System bottles to monitor compliance. Clinic visits included therapy sessions, electrocardiograms, self-report measures, and twice-weekly urine screens. The two groups were equivalent in terms of retention (methylphenidate 48% and placebo 42%) and had similar cocaine use outcomes (40% benzoylecgonine-positive urine screens). There were no significant adverse effects. The doses were sufficient to permit detection of psychoactive effects ("stimulant," "more energy") and side effects ("jitteriness," "eating less") without increased "craving." Additional medications with different effects profiles are being studied to further evaluate the replacement model in cocaine dependence. Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Selegiline is an irreversible selective inhibitor of monoamine oxidase type B (MAO-B) which may affect cocaine addiction through several potential mechanisms. In this study, selegiline transdermal system (STS) was compared to placebo as a treatment for cocaine dependence. This multi-site, double-blind trial of 300 subjects with cocaine dependence assessed the efficacy of selegiline using subject self-reported cocaine use substantiated by urine benzoylecgonine (BE) as the primary outcome measure. Analysis of the data did not show a significant effect for selegiline over placebo. This study does not support a role for selegiline in treating cocaine dependence. The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models. The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p=.91). The majority of the PBO group and the MPH group reported >30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p=.44). Using a combined outcome measure (>30% reduction in ADHD symptoms and CGI <3), the response rates were similar for both groups (28% PBO versus 30% MPH; p=.83). Longitudinal analyses of the urine toxicology data using generalized estimating equations, revealed a decrease in the probability of cocaine positive urine samples during the trial for the MPH group compared to the PBO group (p=.001). Further analysis suggested that for the MPH group, ADHD treatment responders, based on a semi structured clinical interview, were more likely to have a reduction in cocaine use compared to the non-ADHD responders. Although sustained-release MPH did not show superiority over PBO in treating ADHD symptoms, this trial provides some evidence that improvement in ADHD symptoms (clinician rated) among those patients receiving MPH, but not placebo, was associated with a reduction in cocaine use. No medication is currently approved for the treatment of cocaine dependence, but several preclinical and clinical reports suggest agonist-like medications, e.g., amphetamine analogues, may be a productive strategy for medication development.
                This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence.
                A randomized, double-blind, placebo-controlled study served to evaluate three treatment conditions in 82 cocaine-dependent individuals: (1) placebo (0mg, 6x/day; n=27), (2) immediate release (IR) methamphetamine (5mg, 6x/day; n=30), (3) sustained release (SR) methamphetamine (30 mg first pill, 1x/day; 0mg 5x/day; n=25). The study employed a sequential, two-phase design (i.e., 4 weeks of medication and counseling followed by 4 weeks of medication/counseling plus a contingency management procedure).
                Both preparation forms of methamphetamine were well-tolerated, with similar retention to placebo (0mg, 33%; 30 mg IR, 30%, 30 mg SR, 32%). Methamphetamine SR was associated with decreased sleep and increased weight loss. Medication adherence rates were high for the first dose of the day (95%), while adherence for subsequent capsules was lower. Those in the SR condition exhibited consistently lower rates of cocaine-positive urine samples (0mg, 60%; 30 mg IR, 66%; 30 mg SR, 29%), p<0.0001, and reported the greatest reduction in craving for cocaine, p<0.05.
                SR methamphetamine significantly reduced cocaine use and craving. Additional research is warranted to develop and evaluate agonist-like medications that may effectively treat cocaine dependence. Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25-63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence. 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 psychostimulant-dependence treatment. This double-blind placebo-controlled treatment study tested the efficacy of mazindol in currently cocaine-dependent out-patients. Forty-three patients were randomized to mazindol (2 mg QD) vs. placebo treatment for 6 weeks. All patients received weekly group counseling. Patients improved with respect to objective (urine toxicology) and subjective (self-report of times used, dollars spent, craving, etc.) measures. There was no response difference between patients treated with mazindol and those who received placebo. We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study. Outcome measures included cocaine use, level of depression, and psychosocial functioning. Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry. The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed. We conducted a double-blind, randomized clinical trial of mazindol (n = 37) for the prevention of relapse to cocaine abuse in methadone-maintained patients who were in the "action" stage of change, i.e., had a history of cocaine dependence but who had been abstinent for at least 2 weeks prior to entry into the study. Eight-one percent of subjects completed the 12-week course of treatment. Overall, cocaine use during the study was comparatively low-17% of the urine screens submitted were positive for cocaine metabolite. Differences between the mazindol and placebo groups of rates of relapse, number of days to relapse, and cocaine use did not reach statistical significance, but were in the direction of a treatment effect. Results suggest that stage of abstinence initiation may be a potentially useful category to employ as an independent variable in future pharmacotherapy trials for the treatment of cocaine addiction in this patient population. To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data.
                Double-blind randomized placebo-controlled trial.
                Thirty cocaine-dependent injecting drug users.
                Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks.
                Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data.
                Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group.
                A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted. No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy.
                To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals.
                This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB).
                Outpatient clinic at the Veterans Affairs Connecticut Healthcare System.
                A total of 106 opiate-dependent, cocaine-abusing individuals.
                All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study.
                Thrice-weekly urine toxicologic test results for cocaine and heroin.
                Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use.
                These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone. In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, we found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment. Bupropion hydrochloride is a dopamine and norepinephrine reuptake inhibitor which may be an effective treatment for cocaine dependence due to its ability to reverse deficits in dopaminergic functioning that occur in chronic cocaine users. We performed a randomized, double-blind, placebo controlled trial comparing outpatient treatment with bupropion (N = 37) and placebo (N = 33) in combination with standard cognitive behavioral therapy. There were no statistically significant differences between bupropion and placebo in treatment outcomes, including aggregate measures of urine drug screen results (Joint Probability Index at 16 weeks: 0.43 for bupropion and 0.38 for placebo), treatment retention, cocaine craving ratings, and assessments of depressive symptoms. The failure to find an effect for bupropion relative to placebo, when combined with standard cognitive behavioral therapy, dampens enthusiasm for future development of bupropion as a cocaine pharmacotherapy.
This review found mixed results, therefore evidence of the efficacy of psychostimulants for cocaine dependence is inconclusive. Nevertheless promising results exist for methadone maintained dual heroin-cocaine addicts and for some specific drugs such as dexamphetamine and bupropion.