Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse. A pilot trial of topiramate for the treatment of cocaine dependence. Psychotherapy and pharmacotherapy for ambulatory cocaine abusers. Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence. Pharmacological and behavioral treatments of cocaine dependence: controlled studies. Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Treatment responsivity of cocaine-dependent patients with antisocial personality disorder to cognitive-behavioral and contingency management interventions. Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects. Antisocial personality disorder as a prognostic factor for pharmacotherapy of cocaine dependence. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. High-dose naltrexone therapy for cocaine-alcohol dependence.
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. 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. 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. 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. 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. 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. 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 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. 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. 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. 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. 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.
Although caution is needed when assessing results from a limited number of small clinical trials at present there is no current evidence supporting the clinical use of anticonvulsants medications in the treatment of cocaine dependence. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, we need to improve the primary research in the field of addictions in order to make the best possible use out of a single study and to investigate the efficacy of other pharmacological agent.