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Background and Aims: Sustained‐release (SR) formulations of dexamphetamine and mixed amphetamine salts have shown positive effects in the treatment of patients with a cocaine use disorder. We previously demonstrated the efficacy of SR‐dexamphetamine for patients with cocaine dependence in terms of cocaine use reductions. In this secondary analysis, we assessed whether SR‐dexamphetamine treatment also improves the health status of these patients. Design Multi‐centre randomized, double‐blind placebo‐controlled trial. Setting: Four supervised heroin‐assisted treatment (HAT) out‐patient clinics in the Netherlands. In HAT, methadone treatment‐refractory opioid‐dependent patients can self‐administer individually titrated doses of pharmaceutical grade diacetylmorphine, coprescribed with oral methadone. Participants: Seventy‐three cocaine‐dependent patients (90% males; average age = 48.7 years), participating in HAT for their treatment‐refractory comorbid opioid dependence. Interventions: Twelve weeks pharmacotherapy with once‐daily, supervised intake of two tablets of SR‐dexamphetamine (2 × 30 mg/day) or two identical placebo tablets. Measurements Assessment every 4 weeks: cocaine use (time‐line follow‐back), physical health (Maudsley Addiction Profile–Health Symptoms Scale), mental health (Brief Symptom Inventory) and illegal activities (Addiction Severity Index). Primary outcome was 'overall health', a dichotomous, multi‐domain response index based on physical health, mental health and social functioning. Findings Compared with placebo, SR‐dexamphetamine resulted in larger increases in the number of cocaine abstinent days (P = 0.004) and the proportion of overall health treatment responders (P = 0.045) from the 4 weeks preceding baseline to the final 4 weeks of treatment. While the number of cocaine abstinent days was not associated with overall health in the total study sample, it was positively associated with overall health among patients in poor overall health at the start of SR‐dexamphetamine treatment (n = 50), i.e. patients with the potential to improve on this multi‐domain response index (odds ratio = 1.076; 95% confidence interval = 1.025–1.130). Conclusions: SR‐dexamphetamine reduces cocaine use and may improve clinically relevant health‐related outcomes in patients with cocaine dependence who are participating in heroin‐assisted treatment for their comorbid heroin dependence. [ABSTRACT FROM AUTHOR]

Background: High impulsivity and attentional bias are common in cocaine-dependent patients and predict poor treatment outcomes. The pharmacological agent modafinil is studied for its cognitive-enhancing capacities and may therefore improve clinical outcomes in crack-cocaine dependent patients. In this study, we investigated first whether pre-treatment impulsivity and attentional bias predict treatment outcome; next whether the drug modafinil given as an add-on treatment to cognitive behavioural therapy (CBT) improves impulsivity and attentional bias; and last, whether changes in impulsivity and attentional bias are related to improvements in treatment outcome.Methods: Crack-cocaine dependent outpatients (n = 65) were randomised to 12 weeks CBT plus modafinil (400 mg/day) or only CBT. Self-reported impulsivity was assessed at baseline using the Barratt Impulsiveness Scale. At baseline and Week 12, we assessed inhibitory control as a behavioural measure of impulsivity, in terms of cognitive interference (Stroop task) and response inhibition ('stop-signal task'), and attentional bias with the addiction Stroop task. Clinical outcomes were CBT-retention and crack-cocaine use.Results: At baseline, self-reported impulsivity predicted better CBT-retention; low self-reported and behavioural impulsivity and attentional bias predicted less crack-cocaine use. Changes in cognitive performance were not modafinil-related, but most likely due to low adherence. Improvements in impulsivity or attentional bias were not associated with CBT-retention nor changes in crack-cocaine use.Conclusions: Baseline impulsivity and attentional bias predicted clinical outcomes in crack-cocaine dependent patients. There were no firm indications that modafinil reduced impulsivity nor attentional bias in this population. Future studies involving cognitive-enhancing medications should include strategies to optimise adherence, to be better able to evaluate their potential. [ABSTRACT FROM AUTHOR]

Background: Heroin-assisted treatment is effective for methadone treatment-refractory heroin-dependent patients, but continued comorbid cocaine dependence remains problematic. Sustained-release dexamfetamine is a promising agonist pharmacotherapy for cocaine dependence and we aimed to assess its acceptance, efficacy, and safety.Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, patients who were treatment-refractory, as indicated by at least two earlier failed treatments aimed at reducing or abstaining from cocaine use, and who regularly (≥8 days/month) used crack-cocaine were enrolled from four heroin-assisted treatment centres in the Netherlands. Eligible patients were randomly assigned (1:1) to receive either 12 weeks of daily, supervised prescription of 60 mg/day oral sustained-release dexamfetamine or placebo in addition to co-prescribed methadone and diacetylmorphine. Randomisation was done by the collaborating pharmacist, using a computer-generated random number sequence with stratification by treatment centre in blocks of four per stratum. Randomisation was masked to patients, staff, and researchers throughout the study. The primary outcome was the number of self-reported days of cocaine use during study treatment, assessed every 4 weeks. Primary and safety analyses were done in the intention-to-treat population. The study was registered with the European Union Drug Regulating Authorities Clinical Trials (EUdraCT 2013-004024-11) and with The Netherlands Trial Register (NTR2576).Findings: Between Aug 8, 2014, and Feb 27, 2015, 111 patients were assessed for eligibility, of whom 73 were enrolled and randomised; 38 patients were assigned to the sustained-release dexamfetamine group and 35 to the placebo group. Sustained-release dexamfetamine treatment resulted in significantly fewer days of cocaine use than placebo treatment (mean 44·9 days [SD 29·4] vs 60·6 days [24·3], respectively [95% CI of difference 3·1-28·4]; p=0·031; Cohen's standardised effect size d=0·58). One or more adverse events were reported by 28 (74%) patients in the dexamfetamine group and by 16 (46%) patients in the placebo group. Most adverse events were transient and well-tolerated.Interpretation: Sustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management.Funding: Netherlands Organisation for Health Research and Development. [ABSTRACT FROM AUTHOR]

The article discusses the results of an open-label randomised controlled feasibility study of modafinil use for crack-cocaine dependence treatment in the Netherlands. It says that patients were randomised to receive cognitive behavioural therapy (CBT) plus modafinil. Results showed that modafinil did not improve CBT treatment retention.

Abstract: Background: Crack-cocaine dependence is a complex disorder with limited treatment options. Topiramate is one of the promising medications with reported reductions in cocaine use and craving in former studies. The present study evaluated the acceptance and effectiveness of topiramate as an add-on to cognitive behavioral therapy (CBT) in crack-cocaine dependent patients. Methods: Seventy-four crack-cocaine dependent outpatients participated in an open-label, randomized feasibility trial. They were randomized to receive either 12-week CBT plus topiramate (200mg/day) or 12-week CBT only. The primary outcome measure was treatment retention. Secondary outcomes included medication adherence, safety, cocaine and other substance use, health, social functioning, and patient satisfaction. Results: Adherence to topiramate treatment was low. In the intent-to-treat analyses, topiramate neither improved treatment retention nor reduced cocaine and other substance use. Post hoc, exploratory analyses suggested a moderation effect of comorbid opioid dependence, with a significant effect of topiramate on cocaine use reduction only in crack-cocaine dependent patients with comorbid opioid dependence. Conclusions: Topiramate was safe and well-tolerated in this sample of crack-cocaine dependent patients, but efficacy was not supported probably due to low acceptance of the treatment. Given the equivocal results of previous studies and the negative findings in our study, the potential of topiramate in the treatment of cocaine dependence seems limited. [Copyright &y& Elsevier]

The co-occurrence of severe mental illness (SMI) and substance use disorder (SUD) in dual diagnosis patients is common and associated with negative treatment outcomes. Therefore, integrated treatments, combining proven effective mental health and substance abuse interventions, have emerged. However, evidence about the effectiveness of integrated outpatient versus inpatient treatment for dual diagnosis patients from randomised controlled trials is lacking. The aim of the paper is to determine whether integrated outpatient treatment for patients with SMI and SUD is more effective than integrated inpatient treatment. Three months of post-treatment hospitalisation, problem drug use and psychiatric status were assessed in 82 patients with SMI and SUD in a randomised controlled trial (RCT) comparing five months of integrated inpatient treatment (n = 40) with five-months integrated outpatient treatment (n = 42) following a shared one-month inpatient stabilisation phase. No significant differences in outcomes were found between the two treatment conditions using intention-to-treat analyses. However, considerable crossover of patients between treatment conditions occurred. This crossover occurred significantly more in the outpatient treatment group, where patients remained in inpatient treatment longer than the intended one month stabilisation phase. As a consequence, actual time in inpatient treatment did not differ between the study groups. Post hoc analyses showed that baseline patient characteristics did not predict actual time in inpatient treatment. Due to considerable crossover of study participants, we were unable to answer our study question regarding the comparative effectiveness of inpatient versus outpatient treatment. This raises serious questions regarding the feasibility of RCTs investigating inpatient versus outpatient integrated treatment in patients with SMI and co-occurring SUD. [ABSTRACT FROM AUTHOR]