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.
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.
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.