Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials. Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects. Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform. Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse. Contingency management and levodopa-carbidopa for cocaine treatment: a comparison of three behavioral targets. Psychotherapy and pharmacotherapy for ambulatory cocaine abusers. A pilot trial of olanzapine for the treatment of cocaine dependence. Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Pharmacological and behavioral treatments of cocaine dependence: controlled studies. Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study. A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments. High-dose naltrexone therapy for cocaine-alcohol dependence. A randomized placebo-controlled trial of gabapentin for cocaine dependence. A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence. Use of dopamine agonist pergolide in outpatient treatment of cocaine dependence. A pilot trial of topiramate for the treatment of cocaine dependence. Treatment responsivity of cocaine-dependent patients with antisocial personality disorder to cognitive-behavioral and contingency management interventions. Acupuncture for the treatment of cocaine addiction: a randomized controlled trial. Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic.
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. 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 dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities.
                A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan+cognitive behavioral therapy (CBT); or ClinMan+CBT+voucher-based reinforcement therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-min nurse-delivered ClinMan sessions. Weekly, 1-h CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models.
                Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations.
                This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment. 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. New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy. 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. 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. 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. 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 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. 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 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. In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals.
                The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment.
                Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants.
                When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment. This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT).
                Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission.
                Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data.
                Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group. The dopamine agonist pergolide was evaluated in the treatment of 42 men who manifested cocaine dependence in a single-blind, 4-week-long placebo-controlled study, during 1998-1999 in São Paulo, Brazil. The patients were randomly assigned to two groups: the first group received pergolide (0.05-0.2 mg per day) and the second group received placebo (one to four tablets per day). Urine toxicology screens were obtained. The groups were compared in terms of depressive symptoms, "craving," use of cocaine, side effects of medications, results of urine tests, and retention in treatment. At 3 months' follow-up, the participants were reassessed. No differences were found between the two groups. 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. 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. Auricular acupuncture is widely used to treat cocaine addiction in the United States and Europe. However, evidence from controlled studies regarding this treatment's effectiveness has been inconsistent.
                To investigate the effectiveness of auricular acupuncture as a treatment for cocaine addiction.
                Randomized, controlled, single-blind clinical trial conducted from November 1996 to April 1999.
                Six community-based clinics in the United States: 3 hospital-affiliated clinics and 3 methadone maintenance programs.
                Six hundred twenty cocaine-dependent adult patients (mean age, 38.8 years; 69.2% men); 412 used cocaine only and 208 used both opiates and cocaine and were receiving methadone maintenance.
                Patients were randomly assigned to receive auricular acupuncture (n = 222), a needle-insertion control condition (n = 203), or a relaxation control condition (n = 195). Treatments were offered 5 times weekly for 8 weeks. Concurrent drug counseling was also offered to patients in all conditions.
                Cocaine use during treatment and at the 3- and 6-month postrandomization follow-up based on urine toxicology screens; retention in treatment.
                Intent-to-treat analysis of urine samples showed a significant overall reduction in cocaine use (odds ratio, 1.40; 95% confidence interval, 1.11-1.74; P =.002) but no differences by treatment condition (P =.90 for acupuncture vs both control conditions). There were also no differences between the conditions in treatment retention (44%-46% for the full 8 weeks). Counseling sessions in all 3 conditions were poorly attended.
                Within the clinical context of this study, acupuncture was not more effective than a needle insertion or relaxation control in reducing cocaine use. Our study does not support the use of acupuncture as a stand-alone treatment for cocaine addiction or in contexts in which patients receive only minimal concurrent psychosocial treatment. Research will be needed to examine acupuncture's contribution to addiction treatment when provided in an ancillary role. In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.
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Current evidence from randomised controlled trials does not support the use of dopamine agonists for treating cocaine dependence. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment.Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention which was suggested by the previous Cochrane review (Soares 2003), is not supported by the results of this updated review.