Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial. Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects. Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence. Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Psychotherapy and pharmacotherapy for ambulatory cocaine abusers. Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse. Pharmacological and behavioral treatments of cocaine dependence: controlled studies. Treatment responsivity of cocaine-dependent patients with antisocial personality disorder to cognitive-behavioral and contingency management interventions. A randomized, double-blind, placebo-controlled study of ritanserin pharmacotherapy for cocaine dependence. Antisocial personality disorder as a prognostic factor for pharmacotherapy of cocaine dependence. Nefazodone treatment of cocaine dependence with comorbid depressive symptoms. Relapse prevention treatment for cocaine dependence: group vs. individual format. A randomized controlled study of the effectiveness of intensive outpatient treatment for cocaine dependence. Achieving cocaine abstinence with a behavioral approach. Double-blind comparison of carbamazepine and placebo for treatment of cocaine dependence. Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial. High-dose naltrexone therapy for cocaine-alcohol dependence. Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine. Citalopram combined with behavioral therapy reduces cocaine use: a double-blind, placebo-controlled trial. A pilot trial of olanzapine for the treatment of cocaine dependence. Treatment of cocaine-alcohol dependence with naltrexone and relapse prevention therapy. Group counseling versus individualized relapse prevention aftercare following intensive outpatient treatment for cocaine dependence: initial results. Desipramine treatment for cocaine dependence. Role of antisocial personality disorder. A pilot trial of topiramate for the treatment of cocaine dependence. Changes in cocaine use after entry to methadone treatment. Imipramine treatment of cocaine abuse: possible boundaries of efficacy. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Safety and efficacy of L-tryptophan and behavioral incentives for treatment of cocaine dependence: a randomized clinical trial. A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments. A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms. Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials. Effects of combined fluoxetine and counseling in the outpatient treatment of cocaine abusers.
The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders.
                This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial.
                Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p < 0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening.
                Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use. This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients.
                Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month.
                Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed.
                Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence. This study evaluated the efficacy of cognitive-behavioral therapy (CBT) and 12-step facilitation (12SF) in treating cocaine abuse. Participants (N = 128) were randomly assigned to treatment conditions and assessed at baseline and at Weeks 4, 8, 12, and 26. Treatment lasted for 12 weeks. It was hypothesized that participants treated with CBT would be significantly more likely to achieve abstinence from cocaine than participants treated with 12SF. A series of patient-treatment matching hypotheses was also proposed. Across 2 different outcome variables, it was found that participants in CBT were significantly more likely to achieve abstinence than participants in 12SF. In addition, some support for matching hypotheses was found, suggesting that both psychotherapies may be differentially effective for identified subgroups of persons that abuse cocaine. The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence.
                A multi-arm, modified blinded, placebo-controlled design was used.
                The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).
                Participants met criteria for cocaine dependence during a 2-week screening period.
                Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.
                Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.
                None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated.
                This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups. 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. 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. At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers.
                One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment.
                First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management.
                These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers. Motivational interviewing (MI) with personalized feedback, particularly related to biological markers of risk or harm, has been found effective for alcohol use disorders, but has not been fully investigated in cocaine use disorders. A randomized, controlled pilot study evaluating the feasibility and preliminary efficacy of a brief MI intervention using EEG/ERP graphical feedback for cocaine abusers was conducted. Treatment-seeking cocaine abusers (N = 31) were randomly assigned to a two-session MI intervention or a minimal control condition. All participants received EEG assessments at intake and post-treatment. Results indicated that the MI intervention was feasible and the subjective impact of the EEG feedback was positive. Significant group differences in percentage of cocaine positive urine screens across the study were found, favoring the MI group; 84.9% for the control group and 62.6% in the MI group, p < .05. Further research must determine the specific conditions under which MI is most appropriate and efficacious. The cocaine epidemic has stimulated novel treatments aimed at reducing relapse to this extremely addicting drug. After detoxification and standard treatment, former cocaine users continue to exhibit strong cocaine craving and physiological changes when presented with cocaine-related stimuli. Because these conditioned responses may increase the risk of relapse, a new treatment has been developed to extinguish such responses. The extinction process, consisting of repeated presentations of cocaine-related stimuli until the stimuli gradually lose their ability to evoke conditioned responses, is integrated into a comprehensive rehabilitation program. Cocaine dependence is often combined with opiate dependence. Desipramine has been added to methadone maintenance in an attempt to reduce dependence on both substances. Methadone impedes catabolism of desipramine so that relatively low doses of desipramine may produce antidepressant effects and possibly reduce the desire to use cocaine. Preliminary evidence from a placebo-controlled study of desipramine in combination with methadone suggests that desipramine produces significant improvements in psychological functioning, but its effects on reduction of cocaine use are less dramatic. This study compared the efficacy of 2 approaches for the treatment of cocaine dependence among methadone-maintained patients with and without antisocial personality disorder (ASPD). Patients were randomly assigned to 4 study conditions: cognitive-behavioral treatment (CBT), contingency management (CM), CBT with CM, or methadone maintenance. The Structural Clinical Interview for Mental Disorders-IV was administered to 108 patients to assess ASPD. A 2-way analysis of variance showed that patients with ASPD were more likely to abstain from cocaine use during treatment than patients without ASPD. The strong treatment effect for ASPD patients was primarily due to the CM condition. Regression analyses showed that ASPD remained significantly related to CM treatment responsivity while controlling for other factors. Eighty cocaine-dependent individuals enrolled in outpatient treatment took part in a randomized, double-blind, placebo-controlled trial of ritanserin, a 5-HT(2) antagonist, as an adjunct therapy. Participants attended an outpatient day hospital therapy program each day and received tablets containing placebo or 10 mg ritanserin for a 4-week period. Primary outcome measures included retention in treatment, urine drug tests, and self-reports of craving. Secondary outcome measures were depression scores on the Beck and Hamilton inventories, negative mood as measured by the Profile of Mood States, and life functioning as measured by the Addiction Severity Index. Although participants showed improvement over the 4 weeks, there were no group differences on any of the measures. These results fail to support the use of ritanserin as a complement to outpatient psychosocial therapy for cocaine dependence. Pharmacotherapy response was compared in 94 cocaine-abusing methadone patients with (n = 75) and without (n = 19) antisocial personality disorder (ASP), in a 12-week, randomized, double-blind trial using desipramine 150 mg daily (n = 30), amantadine 300 mg daily (n = 33), and placebo (n = 31). Retention was lower for the ASP group (ASP 9.6 weeks vs. non-ASP 11.2 weeks). During the first 2 weeks, there was no significant difference in the percentage of cocaine-free urines between the ASP vs. non-ASP patients (9% vs. 18%), but during the last 2 weeks, the non-ASP patients showed a significantly greater percentage of cocaine-free urines (30% vs. 7%). Placebo-treated patients in both groups demonstrated no significant difference in their urine toxicologies comparing the first to the last two weeks of treatment. However, the percentage of cocaine-free urines increased from 15% to 32% in medicated non-ASP patients, but showed no change in medicated ASP patients. Thus, antisocial personality disorder was a poor prognostic factor for treatment retention and continued cocaine abuse, and medication did not improve treatment outcome for the ASP patients, but did for the non-ASP patients. In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT(2A) receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use.
                An 8-week, double blind, placebo-controlled design was used.
                The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center.
                Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher.
                Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received individual counseling.
                Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning.
                Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use.
                These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels. To investigate the role of treatment modality in relapse prevention treatment, 32 cocaine-dependent subjects were randomly assigned by cohorts to group-based relapse prevention (G-RP) or individually based RP (I-RP). The two RP formats were identical in content, consisting of 12 outpatient treatment sessions over a 2-month period immediately following hospitalization. The proportion of subjects providing cocaine-free urines at the end of RP treatment did not differ between formats; however, G-RP subjects reported using cocaine on significantly fewer days during treatment, and experiencing fewer cocaine-related problems than did I-RP subjects. Follow-up data collected at 12 and 24 weeks' posttreatment revealed no significant differences between RP formats on any cocaine-use outcome measures. Regardless of therapy format. RP treatment was related to statistically significant and sustained improvements in other areas of psychosocial functioning, including addiction severity, coping, and craving for cocaine. The overall findings suggest that the efficacy of relapse prevention training is not limited by therapy format. A randomized controlled study design was used to compare the effectiveness of intensive outpatient treatment with individual outpatient counseling and a combination of individual and group outpatient counseling for cocaine-dependent patients.
                Volunteers for this study were recruited from among first admissions to an inner-city, public-sector outpatient substance abuse clinic. In-treatment, end-of-treatment, and nine-month follow-up assessments were compared for participants randomly assigned for 12 weeks to one of three treatment modalities--weekly individual outpatient counseling, weekly individual counseling plus one weekly group session, or a newly designed intensive group treatment program consisting of three hours of group treatment three days a week.
                Patients who completed the intensive program showed significant improvement from intake to end-of-treatment scores on the Addiction Severity Index, the Beck Depression Inventory, and the Symptom Checklist. At nine-month follow-up, patients who had remained in treatment longer had fewer drug problems, a smaller proportion of positive urine drug screening tests, a better employment status, and fewer psychological problems compared with patients who left treatment earlier. Patients who remained in treatment were also more likely to be attending self-help meetings, continuing in outpatient treatment, or attending school. However, for the 447 patients randomly assigned to the three conditions, there were no significant differences between treatment modalities on any of the variables at nine-month follow-up. The new intensive treatment program was not shown to be superior to more traditional treatment programs. The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals.
                The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens.
                Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group.
                This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence. This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of 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 randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence. We conducted a pilot study (N = 22) comparing the efficacy of desipramine and amantadine for treatment of cocaine dependence in methadone maintenance clients. The study which lasted 12 weeks, was double-blind, randomly assigned, and placebo-controlled. Subjects met DSM-III-R criteria for active cocaine dependence. All three groups' cocaine use, craving, and depressive symptoms declined significantly, but intergroup differences were not significant. Clients receiving desipramine were significantly more likely to remain in treatment and to be cocaine free at study completion. The results emphasize the importance of delivering comprehensive services to the cocaine user in methadone treatment. Further evaluations of these two medications as adjuncts in the treatment of cocaine dependence are needed. Cocaine dependence continues to be a significant problem in the United States, without any approved pharmacotherapy. Promising findings from preclinical research on the effects of cocaine on serotonin lead to examination of selective serotonin reuptake inhibitors (SSRIs) as potential treatments for cocaine dependence with mixed results, possibly due to drug interactions or specifics of concomitant behavioral therapy. The purpose of this study was to examine whether the SSRI citalopram would reduce cocaine positive urines in a 12-week, double-blind placebo-controlled trial. Seventy-six cocaine dependent patients received either citalopram 20 mg per day or placebo along with cognitive behavioral therapy (CBT) and contingency management (CM). Citalopram treated subjects showed a significant reduction in cocaine-positive urines during treatment compared to placebo treated subjects. No differences were noted in retention between the two groups. Side effects reported for citalopram were mild, with none leading to discontinuation of study drug. Results of this study support further examination of citalopram in combination with behavioral therapy as a treatment for cocaine dependence. Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving.
                This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index.
                Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure.
                The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome. This study evaluates whether patients with cocaine-alcohol dependence might benefit from naltrexone (NTX) pharmacotherapy when delivered in conjunction with psychotherapy. Eighty outpatients meeting DSM-IV criteria for alcohol and cocaine dependence were randomly assigned to receive NTX (placebo or 50 mg/d) combined with psychotherapy (Relapse Prevention [RP] or Drug Counseling [DC]) for twelve weeks. It was hypothesized that the skills training focus of RP therapy, in combination with NTX 50 mg/d, would produce greater reductions in cocaine and alcohol use. Outcome measures included self- and objective reports of substance use, treatment retention, medication compliance, and adverse effects. During the first four weeks of treatment, the percentage of cocaine-positive urine screens was significantly lower for those receiving RP therapy (22%) than those receiving DC (47%); however, this difference subsequently diminished. No medication effects were found. All groups reported less alcohol use at the end of treatment. Treatment retention was the same among the groups, with about 33% of the subjects completing all twelve weeks of treatment. The active medication group showed better medication compliance, while the number of adverse events was low overall and not significantly different by group. In conclusion, NTX at 50 mg/d did not reduce cocaine or alcohol use. These findings stand in contrast to previously reported positive findings for NTX and RP in patients with a single diagnosis of cocaine dependence. Ninety-eight male cocaine-dependent patients who completed an intensive outpatient program (IOP) were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP) aftercare. Heavier cocaine and alcohol use during IOP and low self-efficacy predicted more cocaine use during the treatment phase of the study, whereas lifetime diagnoses of alcohol dependence, major depression, and any anxiety disorder predicted less cocaine use. Rates of complete abstinence during the 6-month study period were higher in STND than RP, whereas RP was more effective in limiting the extent of cocaine use in those who used during Months 1-3. Matching analyses indicated patients who failed to achieve remission from cocaine dependence during IOP and those with a commitment to absolute abstinence did better in RP than in STND, whereas patients with other abstinence goals did better in STND than RP. Several differences in experiences before cocaine use and "near-miss" episodes were also identified. As a test of the efficacy of desipramine (DMI) in the treatment of cocaine dependence, 59 cocaine-dependent males, maintained on methadone for the treatment of opiate dependence, completed a 12-week, random-assignment, placebo-controlled trial of this medication. At the end of treatment, there were no overall differences between the placebo and DMI groups on a range of outcome measures, including urine toxicology tests. However, an interaction between psychiatric diagnosis and outcome was seen when the sample was divided into those with (51%) and those without (49%) antisocial personality disorder (ASP). Patients with ASP made few gains with either DMI or placebo. Those without ASP made a number of gains with DMI but not placebo, particularly in the areas of psychiatric symptoms, legal status, and family problems. DMI had a significant effect on the psychiatric symptoms and personal adjustment problems, but not the cocaine use, of non-antisocial cocaine abusers. The negative influence of ASP that has been seen in studies of psychosocial therapies for substance-use disorders may also apply to pharmacological therapies. Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.
                The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).
                Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05).
                Topiramate may be effective for the treatment of cocaine dependence. A cohort sample of 93 addicts admitted to methadone maintenance in four clinics was followed-up for one year to determine change, and predictors of change, in cocaine use. Any use of cocaine in the preceding month decreased from 84% of subjects at admission to 66% at follow-up, and mean days of cocaine use per month for those still using decreased from 16 days to 9 days. Any drug injection in the preceding month decreased from 100% of subjects at admission to 39% at follow-up, among those remaining in the program. Continuance/cessation of cocaine use was not associated with program retention, but cocaine users were more likely to be administratively discharged. Reported symptoms of depression and speedballing at admission were significant predictors of continuance/cessation of cocaine use at follow-up. State-of-the-art cocaine abuse treatment, with attention to treatment of depression, would enhance the value of methadone maintenance for patients with dual heroin/cocaine addiction. A 12-week placebo-controlled, randomized clinical trial was undertaken to evaluate imipramine as a treatment for cocaine abuse, and to examine whether its effect may be limited to subgroups defined by route of use or by diagnosis of depression. One-hundred thirteen patients were randomized, stratified by route of use and depression. All patients received weekly individual counseling. Compared to placebo the imipramine group showed greater reductions in cocaine craving, cocaine euphoria, and depression, but the effect of imipramine on cocaine use was less clear. A favorable response, defined as at least 3 consecutive, urine-confirmed, cocaine-free weeks was achieved by 19% (11/59) of patients on imipramine compared to 7% (4/54) on placebo (P < 0.09). The imipramine effect was greater among nasal users--33% (9/27) response on imipramine vs. 5% (1/22) on placebo (P < 0.02). Response was also more frequent, but not significantly so, among depressed users on imipramine (26%, 10/38) than on placebo (13%, 4/31) (P < 0.19). Response rates were low in intravenous and freebase users and those without depression. Considered together with the literature on desipramine, these data suggest tricyclic antidepressants are not promising as a mainstay of treatment for unselected cocaine abusers. However, tricyclics may be useful for selected cocaine abusers with comorbid depression or intranasal use, or in conjunction with a more potent psychosocial intervention. 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. 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. L-tryptophan(ie, tryptophan)has shown promise as a pharmacotherapy in cocaine addiction treatment. Abstinent contingent voucher incentives have shown efficacy in abstinence initiation and maintenance for treatment of cocaine dependence. The present study evaluated these two approaches singly and in combination in a relapse prevention+treatment design. A double-blind, parallel-group, placebo-controlled design was used. Cocaine-dependent patients(N=199) were stratified and randomized to one of four groups: tryptophan+contingent vouchers, tryptophan+non-contingent vouchers, placebo+contingent vouchers, and placebo+non-contingent vouchers. The study included residential stabilization (4-9 days), where patients achieved initial cocaine abstinence; outpatient treatment evaluation(16 weeks), where patients received medication, vouchers, and urine testing thrice weekly; and disposition. Main outcomes were retention in treatment, urinalysis, self-reported drug use, and self-reported side effects. Tryptophan did not significantly prevent relapse to cocaine use or attenuate cocaine use after relapse. Contingent vouchers significantly increased the time to cocaine relapse and produced less cocaine use relative to non-contingent vouchers. Results demonstrate the sensitivity of this methodology for detecting decreases in cocaine use, as evidenced by significant changes of the contingent voucher conditions; this suggests that tryptophan's lack of efficacy was not due to model insensitivity for detecting significant differences in cocaine use. This study also showed that contingent vouchers were effective in the novel experimental model of relapse prevention. To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.
                A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.
                This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.
                Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures.
                The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.
                Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.
                Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.
                The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment. This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms.
                Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence.
                In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups.
                In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo. The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use.
                The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence.
                In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies.
                L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood.
                These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed. Three methods of analysis were used to determine the effects of the combination of counseling with fluoxetine (20, 40, or 60 mg) and "active" placebo (diphenhydramine, 12.5 mg) randomly assigned. Forty-five cocaine-only dependent subjects were treated as outpatients with "interpersonal" counseling, medication, and drug use monitoring three times per week for up to 12 weeks. Treatment effects were analyzed: first, by comparing the three original assignments and placebo; second, by comparing the placebo group to fluoxetine subjects with detectable fluoxetine/norfluoxetine blood levels and those with no detectable medication blood level; third, by examining relapse prevention versus use cessation through stratifying the subjects into four groups according to fluoxetine or placebo assignment and initial urine cocaine positivity or negativity. All three analyses showed improvement on some measures over time regardless of group assignment. The 60-mg fluoxetine group showed least effectiveness, the group with detectable blood levels had less cravings, and the fluoxetine subjects who were abstinent at the start of treatment were somewhat less likely to avoid relapse than those on placebo.
At the current stage of evidence data do not support the efficacy of antidepressants in the treatment of cocaine abuse/dependence. Partially positive results obtained on secondary outcome measures, such as depression severity, do not seem to be associated with an effect on direct indicators of cocaine abuse/dependence. Antidepressants cannot be considered a mainstay of treatment for unselected cocaine abusers/dependents.