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Introduction: We investigated the value of systematic client feedback in youth mental health and addiction care. In the present study, we examined whether a client feedback intervention would result in improved therapeutic alliance and treatment outcomes. Methods: Two hundred and four adolescents participated in the study using a – non-randomized – between-group A/B design. In the first study group, 127 patients were offered 4 months of treatment as usual (TAU), and in the second study group, 77 patients received the client feedback intervention as an add-on to TAU during 4 months. Results: Youths who received systematic client feedback in addition to TAU did not show better treatment outcomes or better alliance ratings after 4 months than youths receiving TAU only. Sensitivity analyses, in which we compared the more adherent patients of the second study group with patients receiving TAU, did not show significant beneficial effects of client feedback either. Also, the client feedback intervention did not result in lower rates of early treatment drop-out. Discussion/Conclusion: Our results cautiously suggest that client feedback does not have incremental effects on alliance and the treatment outcome for youth in mental health and addiction treatment. Moreover, our study highlights the challenges of implementing client feedback in clinical practice and the need for additional research addressing these challenges.

The therapeutic alliance is considered to play an important role in youth treatment. The commonly used versions of the Working Alliance Inventory (WAI) are based on Bordin’s three-dimensional alliance model. However, previous psychometric studies of the WAI did not find this three-dimensional structure in youth psychotherapy. These earlier findings may indicate different perceptions of the alliance by adolescent versus adult patients, but may also be due to methodological shortcomings. The current study aims to address previous study limitations by evaluating the factor structure of the most recent and refined version of the WAI in youth treatment and using multilevel analysis to address the hierarchical structure of the alliance data. We examined the psychometric properties of the youth (n = 203) and therapist (n = 62) versions of the short revised WAI in youth mental health and addiction care and tested the three multilevel models of alliance at start of treatment and 2-month follow-up. Our results suggests a two-factor model for youth and a three-dimensional model for their therapist at both time points. Since this is the first study that finds a best fit for a two-dimensional construct of alliance in youth, more research is needed to rule out whether the differences in alliance dimensions are due to measurement differences between the WAI-SR for youth and therapists or whether youth and their therapists truly differ in their perceptions of the concept of alliance.

Aim To explore whether combined interventions i.e. psychotherapeutic plus psychosocial interventions are more effective than monotherapies in the treatment of alcohol use disorders. Methods Systematic review of the results of randomized controlled trials that compared combined therapies with monotherapies (either pharmacotherapy or psychotherapy). Results The search resulted in 28 eligible studies. Data from these RCTs showed that 10 out of 19 RCTs (53%) demonstrated an added value of combined therapy (psychotherapy + pharmacotherapy) compared to psychotherapy only, whereas only three out of nine RCTs (33%) comparing combined therapy with pharmacotherapy showed a possible added value for combined therapy. Conclusions Pharmacotherapy is effective to treat AUD with or without psychotherapy and that psychotherapy can best be offered in combination with pharmacotherapy.

Background: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.Objectives: We compared mental health outcomes between different opioid agonis...

Vadim Yuferov,1,* Eduardo R Butelman,1,* Matthew Randesi,1 Wim van den Brink,2 Peter Blanken,3 Jan M van Ree,4 Mary Jeanne Kreek1 1Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, 10065, USA; 2Amsterdam University Medical Centers, Location Academic Medical Center, Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands; 3Parnassia Addiction Research Centre, The Hague, The Netherlands; 4Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands*These authors contributed equally to this workCorrespondence: Eduardo R ButelmanLaboratory on the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USATel +1 212 327-8490Fax +1 212 327-8574Email butelme@rockefeller.eduIntroduction: A functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity. We hypothesize that SLC6A4 variants are associated with cocaine exposure in subjects with an opioid dependence diagnosis (OD), and also in non-dependent opioid users (NOD). Other single nucleotide polymorphisms (SNPs) of SLC6A4 may also be likewise associated.Materials and Methods: This study determined whether variants of the SLC6A4 promoter repeats and two intronic SNPs, rs16965628 and rs2066713, are associated with categorical diagnoses of opioid dependence (DSM-IV criteria) and with dimensional aspects of cocaine use, in a Caucasian cohort (n=591). Three groups of subjects were examined: (1) 276 subjects with opioid dependence diagnosis (OD); (2) 163 subjects who had used opioids for non-medical reasons but never had an opioid dependence diagnosis (NOD); (3) 152 healthy controls (HC).Results: Aside from high exposure to heroin in the OD group, relatively high exposure to cocaine was detected in both OD and NOD groups. The SERT repeat genotype (classified as “long-long” [LL] versus ”short-long” plus “short-short” [SL+SS]) was not associated with categorical opioid dependence diagnoses. A nominally significant association was identified with the [SL+SS] genotype of SLC6A4 and cocaine KMSK scores ≥“cutpoint” for a cocaine dependence diagnosis (p=0.026). The [SL+SS] genotype was associated with more rapid cocaine escalation than the LL genotype. No significant associations of rs16965628 and rs2066713 SNPs were found overall.Conclusion: The functional SERT promoter tandem repeat genotype may be associated to heavy cocaine exposure and more rapid escalation of cocaine use, in persons with and without opioid dependence diagnosis.Keywords: cocaine, serotonin transporter, SLC6A4, KMSK scale, escalation

Aim: Heroin addiction is a chronic, relapsing disease that has genetic and environmental, including drug-induced, contributions. Stress influences the development of addictions. This study was conducted to determine if variants in stress-related genes are associated with opioid dependence (OD). Patients & methods: One hundred and twenty variants in 26 genes were analyzed in 597 Dutch subjects. Patients included 281 OD in methadone maintenance with or without heroin-assisted treatment and 316 controls. Results: Twelve SNPs in seven genes showed a nominally significant association with OD. Experiment-wise significant associations (p < 0.05) were found for three SNP pairs, through an interaction effect: NPY1R/ GAL rs4691910/rs1893679, NPY1R/ GAL rs4691910/rs3136541 and GALR1/GAL rs9807208/rs3136541. Conclusion: This study lends more evidence to previous reports of association of stress-related variants with heroin dependence.

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.

ObjectiveThere is a dearth of high-quality systematic evidence on the impact of opioid substitution medications on mental health. We compared mental health outcomes between opioid medications and placebo/waitlist, and between different opioids.MethodsThis systematic review and meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with a placebo/waitlist in substitution treatment of patients with opioid use disorder, and reported at least one mental health outcome on a span of more than 1-month post baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. Primary outcomes were comparison of depressive symptoms and overall mental health between opioids and placebo/waitlist. Random effects model was used for all the meta-analysis.ResultsNineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%)= −0.61 (−1.20, −0.11)), DAM (−1.40 (−2.70, −0.23)), and methadone (−1.20 (−2.30, −0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (−0.23 (−0.34, −0.13)).ConclusionsIt appears that opioid medications improve mental health independent of psychosocial services. Potential contribution of other factors needs to be further investigated.

We investigated the potential role of first-session therapeutic alliance ratings to serve as an early marker of treatment outcome in youth mental health and addiction treatment. The present study is among the first to incorporate both a youths’ and a therapists’ perspective of the therapeutic alliance in order to maximize predictive value of the alliance for treatment outcome. One hundred and twenty-seven adolescents participated in a multi-site prospective naturalistic clinical cohort study, with assessments at baseline and at 4 months post-baseline. Main outcome measure was favorable or unfavorable treatment outcome status at 4-month follow-up. Early therapeutic alliance had a medium and robust association with treatment outcome for youth’ (b = 1.29) and therapist’ (b = 1.12) perspectives and treatment setting. Based on the two alliance perspectives four subgroups were distinguished. Incorporating the alliance-ratings from both perspectives provided a stronger predictor of treatment outcome than using one perspective. Youth with a strong alliance according to both perspectives had an eightfold odds of favorable treatment outcome compared with youth with a weak alliance according to both perspectives. The association between therapeutic alliance and treatment outcome in youth mental health and addiction treatment may be substantially stronger than earlier assumed when both a youths’ and therapists’ perspective on alliance is considered.

The dynorphin/kappa opioid receptor (Dyn/KOR) system is involved in reward processing and dysphoria/anhedonia. Exposure to mu-opioid receptor agonists such as heroin increases expression of the prodynorphin gene (PDYN) in the brain. In this study in a Caucasian cohort, we examined the association of the functional PDYN 68-bp repeat polymorphism with opioid use disorders. In this case-control study, 554 subjects with Caucasian ancestry (142 healthy controls, 153 opioid-exposed, but never opioid dependent, NOD, and 259 with an opioid dependence diagnosis, OD) were examined for association of the PDYN 68-bp repeats with the diagnosis of opioid dependence (DSM-IV criteria), with a dimensional measure of heroin exposure (KMSK scale), and age trajectory parameters of heroin use (age of heroin first use, and age of onset of heaviest use). The PDYN 68-bp repeat genotype (classified as: “short-short” [SS], “long-long” [LL], and “short-long” [SL], based on the number of repeats) was not associated with categorical opioid dependence diagnoses. However, the LL genotype was associated with later age of first heroin use than the SS + SL genotype (19 versus 18 years; p < 0.01). This was also confirmed by a significant positive correlation between the number of repeats and the age of first use of heroin, in volunteers with OD (Spearman r = 0.16; p = 0.01). This suggests that the functional PDYN 68-bp repeat genotype is associated with the age of first use of heroin in Caucasians diagnosed with opioid dependence.

Summary 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.

Heroine op medisch voorschrift (HMV) is een effectieve behandeling voor methadonresistente opiaatverslaafden, maar hun bijkomend cocainegebruik blijft vaak problematisch. In een gerandomiseerd, dubbelblind, placebogecontroleerd onderzoek bestudeerden de auteurs de acceptatie, effectiviteit en veiligheid van 60 mg dexamfetamine met vertraagde afgifte (‘slow-release’; SR) als substitutie voor crackcocaine bij deze groep HMV-patienten. Gedurende twaalf weken ontvingen deelnemers dagelijks, parallel aan hun behandeling met heroine en methadon, 60 mg dexamfetamine SR of een identiek lijkende placebo. Er werden 111 patienten van vier HMV-units gescreend voor deelname, van wie er 73 instroomden in het onderzoek: 38 naar de dexamfetaminegroep en 35 naar de controlegroep. Vergeleken met een placebo verminderde inname van dexamfetamine SR het aantal dagen cocainegebruik. Op dagen dat er toch gebruikt werd, beperkte de dexamfetamine SR het aantal momenten van gebruik. De bijwerkingen waren meestal mild en van voorbijgaande aard. De auteurs concluderen dat dexamfetamine SR een goed geaccepteerde, effectieve en veilige behandeling is voor chronische cocaineafhankelijkheid bij patienten die HMV krijgen. Toekomstig onderzoek zou zich moeten richten op een bredere groep patienten met verslaving aan cocaine of andere stimulantia, die minder strikt behandeld worden dan bij HMV.

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.

Background Offering financial incentives is an effective intervention for improving adherence in patients taking antipsychotic depot medication. We assessed whether patients’ motivation for treatment might be reduced after receiving financial rewards. Methods This study was part of Money for Medication, a multicentre, open-label, randomised controlled trial, which demonstrated the positive effects of financial incentives on antipsychotic depot compliance. Three mental healthcare institutions in Dutch secondary psychiatric care services participated. Eligible patients were aged 18–65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. For 12 months, patients were randomly assigned either to treatment as usual (control group) or to treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group). They were followed up for 6 months, during which time no monetary rewards were offered for taking antipsychotic medication. To assess treatment motivation after 0, 12 and 18 months, interviews were conducted using a supplement to the Health of the Nation Outcome Scales (HoNOS) and the Treatment Entry Questionnaire (TEQ). Results Patients were randomly assigned to the intervention (n = 84) or the control group (n = 85). After 12 months, HoNOS motivation scores were available for 131 patients (78%). Ninety-one percent of the patients had no or mild motivational problems for overall treatment; over time, there were no significant differences between the intervention and control groups. TEQ data was available for a subgroup of patients (n = 61), and showed no significant differences over time between the intervention and control groups for external motivation (β = 0.37 95% CI: -2.49 – 3.23, p = 0.799); introjected motivation (β = − 2.39 95% CI: -6.22 – 1.44, p = 0.222); and identified motivation (β = − 0.91 95% CI: -4.42 – 2.61, p = 0.613). After the 6-month follow-up period, results for the HoNOS and TEQ scores remained comparable. Conclusions Offering financial incentives for taking antipsychotic depot medication does not reduce patients’ motivation for treatment. Trial registration Netherlands Trial registration, number NTR2350.

Network theory, as a theoretical and methodological framework, is energizing many research fields, among which clinical psychology and psychiatry. Fundamental to the network theory of psychopathology is the role of specific symptoms and their interactions. Current statistical tools, however, fail to fully capture this constitutional property. We propose community detection tools as a means to evaluate the complex network structure of psychopathology, free from its original boundaries of distinct disorders. Unique to this approach is that symptoms can belong to multiple communities. Using a large community sample and spanning a broad range of symptoms (Symptom Checklist-90-Revised), we identified 18 communities of interconnected symptoms. The differential role of symptoms within and between communities offers a framework to study the clinical concepts of comorbidity, heterogeneity and hallmark symptoms. Symptoms with many and strong connections within a community, defined as stabilizing symptoms, could be thought of as the core of a community, whereas symptoms that belong to multiple communities, defined as communicating symptoms, facilitate the communication between problem areas. We propose that defining symptoms on their stabilizing and/or communicating role within and across communities accelerates our understanding of these clinical phenomena, central to research and treatment of psychopathology.

Objective Offering a financial incentive (‘Money for Medication’) is effective in improving adherence to treatment with depot antipsychotic medications. We investigated the cost-effectiveness in terms of medical costs and judicial expenses of using financial incentives to improve adherence. The effects of financial incentives on depot medication adherence were evaluated in a randomised controlled trial. Patients in the intervention group received €30 a month over 12 months if antipsychotic depot medication was accepted. The control group received mental health care as usual. For 133 patients outcomes were calculated based on self-reported service use and delinquent behaviour and expressed as standard unit costs to value resource use. Results The financial incentive resulted in higher average costs related to mental health care (€449.6 versus €355.7). and lower medical costs related to other healthcare services (€52.0 versus €78.4). Relevant differences in social costs related to delinquent behaviour were not found. Although wide confidence intervals indicate uncertainty, incremental cost-effectiveness ratio’s (ICER) indicate that it costs €2080 for achieving a 20% increase in adherence or €3332 for achieving over 80% adherence. In sum, offering money as financial incentive for increasing compliance did not lead to an overall cost reduction as compared to care as usual. Trial registration NTR2350, 01 June 2010

Introduction Research has shown that sustained-release (SR) dexamphetamine is a promising agonist treatment for cocaine dependence. However, little is known about the pharmacokinetics (PKs) of SR oral dexamphetamine. This study examined the PKs of a new SR dexamphetamine formulation in cocaine plus heroin-dependent patients currently in heroin-assisted treatment. Methods The study was designed as an open-label PK study in 2 cohorts: n = 5 with once daily 60 mg and n = 7 with once daily 30 mg SR oral dexamphetamine. Five days of blood plasma dexamphetamine concentrations measured with liquid chromatography–mass spectrometry with PK parameter estimates using noncompartmental analysis. Results Twelve cocaine-dependent plus heroin-dependent patients in heroin-assisted treatment were included. The initial cohort 1 dose of 60 mg once daily was adjusted to 30 mg after mild to moderate adverse events. After oral administration, tmax values (coefficient of variation %) were 6.0 (17.0%) and 6.3 (16.3%) hours and t1/2 were 11 (24.6%) and 12 (25.4%) hours for 60 mg and 30 mg SR dexamphetamine, respectively. At steady state, CSSmax values were reached at 100 (27.5%) ng/mL and 58.4 (14.4%) ng/mL, whereas CSSmin values were 39.5 (38.9%) ng/mL and 21.8 (19.8%) ng/mL for 60 mg and 30 mg, respectively. Conclusions The investigated SR formulation of dexamphetamine showed favorable slow-release characteristics in cocaine and heroin-dependent patients. A dose-proportional steady-state concentration was achieved within 3 days. These findings support the suitability of the SR formulation in the treatment of cocaine dependence.

Background A randomized controlled trial ‘Money for Medication’(M4M) was conducted in which patients were offered financial incentives for taking antipsychotic depot medication. This study assessed the attitudes and ethical considerations of patients and clinicians who participated in this trial. Methods Three mental healthcare institutions in secondary psychiatric care in the Netherlands participated in this study. Patients (n = 169), 18–65 years, diagnosed with schizophrenia, schizoaffective disorder or another psychotic disorder who had been prescribed antipsychotic depot medication, were randomly assigned to receive 12 months of either treatment as usual plus a financial reward for each depot of medication received (intervention group) or treatment as usual alone (control group). Structured questionnaires were administered after the 12-month intervention period. Data were available for 133 patients (69 control and 64 intervention) and for 97 clinicians. Results Patients (88%) and clinicians (81%) indicated that financial incentives were a good approach to improve medication adherence. Ethical concerns were categorized according to the four-principles approach (autonomy, beneficence, non-maleficence, and justice). Patients and clinicians alike mentioned various advantages of M4M in clinical practice, such as increased medication adherence and improved illness insight; but also disadvantages such as reduced intrinsic motivation, loss of autonomy and feelings of dependence. Conclusions Overall, patients evaluated financial incentives as an effective method of improving medication adherence and were willing to accept this reward during clinical treatment. Clinicians were also positive about the use of this intervention in daily practice. Ethical concerns are discussed in terms of patient autonomy, beneficence, non-maleficence and justice. We conclude that this intervention is ethically acceptable under certain conditions, and that further research is necessary to clarify issues of benefit, motivation and the preferred size and duration of the incentive. Trial registration Nederlands Trial Register, number NTR2350. Electronic supplementary material The online version of this article (10.1186/s12888-017-1485-x) contains supplementary material, which is available to authorized users.

Provision of financial incentives is a promising intervention for improving adherence in patients taking antipsychotic medication. We aimed to assess the effectiveness of this intervention for improving adherence to antipsychotic depot medication in patients with psychotic disorders, irrespective of their previous compliance.We did this multicentre, open-label, randomised controlled trial at three mental health-care institutions in secondary psychiatric care services in the Netherlands. Eligible patients were aged 18-65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. Patients were randomly assigned (1:1), via computer-generated randomisation with a block size of four, to receive 12 months of either treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group) or treatment as usual alone (control group). Randomisation was stratified by treatment site and suspected prognostic factors: sex, comorbid substance-use disorder (absent vs present), and compliance with antipsychotic medication in the 4 months before baseline (50% vs ≥50%). Patients, clinicians, interviewers, and research assistants were masked to group allocation before, but not after, group assignment. The primary outcome was the Medication Possession Ratio (MPR), defined as the number of depots of antipsychotic medication received divided by the total number of depots of antipsychotic medication prescribed during the 12 month intervention period. Patients were followed up for 6 months, during which time no monetary rewards were offered for taking antipsychotic medication. We did analysis by intention to treat. This trial is registered with the Nederlands Trial Register, number NTR2350.Between May 21, 2010, and Oct 15, 2014, we randomly assigned 169 patients to the intervention group (n=84) or the control group (n=85). Primary outcome data were available for 155 (92%) patients. At baseline, the mean MPR was 76·0% (SD 28·2%) in the intervention group versus 77·9% (28·5%) in the control group. At 12 months, the mean MPR was higher in the intervention group (94·3% [SD 11·3%]) than in the control group (80·3% [19·1%]), with an adjusted difference of 14·9% (95% CI 8·9-20·9%; p0·0001). This difference was maintained throughout the 6 month follow-up period: mean MPR of 86·6% (SD 22·2%) in the intervention group versus 76·0% (22·7%) in the control group (adjusted difference 6·5%, 95% CI 2·0-10·9; p=0·047).Financial incentives are an effective way of improving adherence to antipsychotic depot medication among patients with psychotic disorders. Further research is needed to study the long-term effects of this intervention.Dual Diagnosis Center.

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 (200 mg/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.

Background Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. Aims This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. Methods Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. Results Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. Conclusions Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness).

Aims: Age of onset is an important criterion to distinguish subgroups of alcohol-dependent patients. This study investigated physical and mental health and social functioning of older inpatients with early (age Methods: In a specialized detoxification ward for older patients in The Hague, the Netherlands, 157 older alcohol-dependent inpatients (38% women, mean age 62.7 ± 6.5) were interviewed with the European version of the Addiction Severity Index. Results: As a group, older alcohol-dependent patients had substantial physical, mental and social problems, which were largely independent of the age of onset of alcohol dependence. Patients with early-onset alcohol dependence had more chronic medical problems and more suicidal thoughts than patients with late-onset alcohol dependence. The very-late-onset group did not significantly differ from the other two groups in any of the variables under study. Conclusions: Despite previous studies showing more favourable outcomes for the (very) late-onset compared to the early-onset alcohol-dependent group, their comorbid (mental) health and social problems are in many respects similar, and require careful assessment and treatment. This may be crucial for successful treatment and improving quality of life in these patients.

This book provides an up-to-date, comprehensive treatment of the variables and processes of microclimate and local climate, including radiation balance and energy balance. It describes and explains the climate within the lower atmosphere and upper soil, the region critical to life on Earth. Topics that are covered include not only the physical processes that affect microclimate, but also biological processes that affect vegetation and animals, including people. A geographic tour of the microclimates of the major ecosystems around the world is included. All major biomes and surface types, including urban areas, are examined, and the effects of climate change on microclimate are described. This book is invaluable for advanced students and researchers in climatology in departments of environmental science, geography, meteorology, agricultural science, and forestry.

Ernst L Noordraven,1,2 André I Wierdsma,2 Peter Blanken,3 Anthony F T Bloemendaal,1 Cornelis L Mulder2,4 1Dual Diagnosis Centre (CDP), Parnassia Psychiatric Institute, the Hague, 2Department of Psychiatry, Erasmus University Medical Center, Rotterdam, 3Parnassia Addiction Research Centre (PARC), Parnassia Psychiatric Institute, the Hague, 4Bavo-Europoort Mental Health Care, Parnassia Psychiatric Institute, Rotterdam, the Netherlands Background: Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Methods: Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Results: Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Conclusion: Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed. Keywords: noncompliance, psychotic disorder, illness insight, motivation, depot medication, schizophrenia

Aims To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use. Design Multi-center, open-label, parallel group, randomized controlled trial. Setting Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006–January 2011. Participants 214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use. Interventions Routine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT + CM and HAT-only, respectively. Measurements Primary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response. Findings In an intention-to-treat analysis, HAT + CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B) = 2.34, 95%-CI: 1.70–3.23; p

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 wer...

The present study investigated the effects of added outpatient services aimed at reintegration assistance and prolonged aftercare on continuity of care and risk of re-hospitalization among patients suffering from both a severe mental illness and a substance use disorder. Administrative data on inpatient and outpatient care of all patients with at least one inpatient treatment episode at the treatment facility for dual diagnosis patients (CDP) of the Parnassia Bavo Psychiatric Institute in The Hague were analyzed (n = 616). The CDP began in 1996 as an inpatient service. In early 1999, the CDP was expanded by outpatient services. The time between discharge and readmission was estimated in a survival time analysis in connection with calendar year (1996–2006) and patient's characteristics. No consistent or substantial differences in the duration of first in-hospital stay at the CDP could be established. The time from admission to enrollment in an outpatient program decreased and the number of outpatient days ...

Aims: To investigate in heroin-assisted treatment (HAT) compared to methadone maintenance treatment (MMT): the course of heroin craving and illicit heroin use, their mutual association, and their association with multi-domain treatment response. Design: RCTs on the efficacy of 12 months co-prescribed injectable or inhalable HAT compared to 12 months continued oral MMT. Setting: Outpatient treatment in MMT- or specialized HAT-centers in the Netherlands. Participants: Chronic, treatment-refractory heroin dependent patients (n=73). Study parameters: General craving for heroin (Obsessive Compulsive Drug Use Scale): self-reported illicit heroin use; multi-domain treatment response in physical, mental and social health and illicit drug use. Findings: The course of heroin craving and illicit heroin use differed significantly, with strong reductions in HAT but not in MMT. General heroin craving was significantly related to illicit heroin use. Heroin craving was not and illicit heroin use was marginally related to multi-domain treatment response, but only in MMT and not in HAT. Conclusions: Heroin craving and illicit heroin use were significantly associated and both strongly decreased in HAT but not in MMT. Craving was not related to multi-domain treatment response and illicit heroin use was marginally related to treatment response in MMT, but not in HAT. The latter was probably due to the strong reduction in illicit heroin use in most patients in HAT and the small sample size of the sub-study. It is hypothesized that the strong reductions in craving for heroin in HAT are related to the stable availability of prescribed, pharmaceutical grade heroin. (C) 2011 Elsevier Ireland Ltd. All rights reserved

BACKGROUND: To meet the treatment needs of the growing number of adolescents who seek help for cannabis use problems, new or supplementary types of treatment are needed. We investigated whether multidimensional family therapy (MDFT) was more effective than cognitive behavioral therapy (CBT) in treatment-seeking adolescents with a DSM-IV cannabis use disorder in The Netherlands. METHODS: One hundred and nine adolescents participated in a randomized controlled trial, with study assessments at baseline and at 3, 6, 9 and 12 months following baseline. They were randomly assigned to receive either outpatient MDFT or CBT, both with a planned treatment duration of 5-6 months. Main outcome measures were cannabis use, delinquent behavior, treatment response and recovery at one-year follow-up, and treatment intensity and retention. RESULTS: MDFT was not found to be superior to CBT on any of the outcome measures. Adolescents in both treatments did show significant and clinically meaningful reductions in cannabis use and delinquency from baseline to one-year follow-up, with treatment effects in the moderate range. A substantial percentage of adolescents in both groups met the criteria for treatment response at month 12. Treatment intensity and retention was significantly higher in MDFT than in CBT. Post hoc subgroup analyses suggested that high problem severity subgroups at baseline may benefit more from MDFT than from CBT. CONCLUSIONS: The current study indicates that MDFT and CBT are equally effective in reducing cannabis use and delinquent behavior in adolescents with a cannabis use disorder in The Netherlands. Language: en

Since the initial Swiss heroin-assisted treatment (HAT) study conducted in the mid-1990s, several other jurisdictions in Europe and North America have implemented HAT trials. All of these studies embrace the same goal-investigating the utility of medical heroin prescribing for problematic opioid users-yet are distinct in various key details. This paper briefly reviews (initiated or completed) studies and their main parameters, including primary research objectives, design, target populations, outcome measures, current status and-where available-key results. We conclude this overview with some final observations on a decade of intensive HAT research in the jurisdictions examined, including the suggestion that there is a mounting onus on the realm of politics to translate the-largely positive-data from completed HAT science into corresponding policy and programming in order to expand effective treatment options for the high-risk population of illicit opioid users.

Objective: To determine the patterns of acquisitive crime during methadone maintenance treatment among chronic, treatment-resistant heroin users eligible for heroin assisted treatment in the Netherlands. Methods: We retrospectively assessed the type and number of illegal activities during 1 month of standard methadone maintenance treatment in 51 patients prior to the start of heroin assisted treatment. Data were collected using a semi-structured interview focussed on crime with special emphasis on property crime. Volume analyses consisted of frequencies and descriptives of mean numbers of offences per day and per type. Results: In a Dutch population of problematic drug users eligible for and prior to commencing heroin assisted treatment, 70% reported criminal activities and 50% reported acquisitive crimes. Offending took place on 20.5 days per month with on average 3.1 offences a day. Acquisitive crime consisted mainly of shoplifting (mean 12.8 days, 2.2 times/day) and theft of bicycles (mean 5.8 days, 2.4 times/day); theft from a vehicle and burglaries were committed less frequently. The majority of these patients (63%) reported to have started offending in order to acquire illicit drugs and alcohol. Conclusion: During methadone maintenance treatment, 50% of criminally active, problematic heroin users eligible for heroin assisted treatment reported acquisitive crime. Shoplifting, thefts and/or other property crimes were committed on average two to three times on a crime day. This study discusses that the detail provided by self-reported crime data can improve cost estimates in economic evaluations of heroin assisted treatment. © 2006 Elsevier Ireland Ltd. All rights reserved.

Background: Persistent cue reactivity to drug-related stimuli is a well-known phenomenon among abstinent drug users and has been found to be a predictor of relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by exposing abstinent drug users to conditioned drug-related stimuli while preventing their habitual response, i.e. drug use. Methods: 127 abstinent heroin-dependent Dutch inpatients were randomized to CET (n = 65; 55 completers) and placebo psychotherapy treatment (PPT) (n = 62; 59 completers). It was examined whether CET would lead to a decrease in drug-related cue reactivity (using mixed-design ANOVA) and subsequently to lower dropout and relapse rates (using logistic regression) compared to PPT. Results: Both groups responded with a similar decrease in self-reported cue reactivity (craving, mood). The CET group did show a significant decrease in physiological reactivity (skin conductance) compared to PPT. However, dropout and relapse rates were, contrary to our expectations, significantly higher in the CET group. Conclusions: This is the first randomized controlled trial showing that CET, compared to a non-specific psychotherapy, might increase dropout and relapse rates among abstinent heroin-dependent clients in a drug-free setting. Caution is warranted when applying CET in this specific context.

Background Crack-cocaine dependence is a serious disorder with no approved pharmacological treatment. Modafinil is a promising medication with increased cocaine abstinence and reduced craving in some previous studies. In the present study, we examined the acceptance, safety and potential benefits of modafinil as an add-on treatment to cognitive behavioural therapy (CBT) in crack-cocaine dependent patients. Methods Sixty-five crack-cocaine dependent outpatients participated in an open-label, randomised feasibility trial. Patients were randomised to receive either 12-week individual CBT plus 400 mg/day modafinil or 12-week individual CBT only. The primary outcome measure was CBT treatment retention. Secondary outcomes included modafinil adherence, tolerability and safety, use of cocaine and other substances, cocaine craving, health, social functioning and patient satisfaction. Results Modafinil adherence was low, with only 10% treatment completers. Intent-to-treat analyses showed that modafinil did not improve CBT treatment retention or any of the secondary cocaine-related outcomes. Both groups showed similar, large reductions in cocaine use during the study treatment. Post hoc exploratory analyses within the CBT plus modafinil group showed significantly larger baseline to week 12 reductions in cocaine use days in high (⩾ 8 weeks) modafinil adherent patients. Conclusions Acceptance and benefits of modafinil were not demonstrated in the present study. Since reduction in cocaine use was observed in high modafinil adherent patients, further research in the treatment of cocaine dependence, in which modafinil adherence is optimised, is warranted.

Objective: To evaluate the validity of the EuroQol (EQ-5D) in a population of chronic, treatment-resistant heroin-dependent patients. Methods: The EQ-5D is studied relative to the Maudsley Addiction Profile (MAP), the Symptom Checklist (SCL-90) and the European Addiction Severity Index (EuropASI) which were used to assess the participant’s physical functioning, mental health and social integration, respectively. Data were gathered from 430 patients participating in the Dutch heroin trials with an intended 12-month treatment period. The EQ-5D was used as a separate health outcome measure. Statistical analyses were conducted using Spearman’s and Pearson’s correlations. Results: The EQ-5D dimensions mobility, self-care and usual activities generally showed low correlations with relevant parameters of the MAPHSS, SCL-90 and EuropASI (r = 0.132–0.369). The EQ-5D dimension pain/discomfort showed low to moderate hypothesized correlations with all disease-specific measures ( r = 0.153–0.496). The EQ-5D dimension anxiety/depression showed moderate to high correlations with the SCL-90 (including the sum score) and some of the EuropASI parameters (r = 0.133–0.615). The EQ-5D utility scores were moderately correlated with the MAP-HSS (r = −0.468) and the SCL-90 (r = −0.491) total score and with response to treatment at month 12. Conclusion: The majority of hypothesized associations between the EQ-5D and the disease or domain-specific measures could be confirmed. The validity of the EQ-5D-based utility score appears to be suitable in the evaluation of chronic, heroin-dependent populations. © 2005 Elsevier Ireland Ltd. All rights reserved.

Cue exposure therapy is seen as a potentially effective treatment for addictive disorders. Drug‐dependent clients are repeatedly exposed to drug‐related stimuli and prevented from using drugs in an attempt to reduce reactivity to these stimuli. The present article gives an overview of cue reactivity models on which cue exposure therapy is based. An example of cue exposure practice is given, with a focus on opiate addiction. It is concluded that the few controlled studies that have been done do not show support for cue exposure therapy as an effective treatment for addictive disorders.

There are an estimated several million crack-cocaine users globally; use is highest in the Americas. Most crack users are socio-economically marginalized (e.g., homeless), and feature elevated risks for morbidity (e.g., blood-borne viruses), mortality and crime/violence involvement, resulting in extensive burdens. No comprehensive reviews of evidence-based prevention and/or treatment interventions specifically for crack use exist. We conducted a comprehensive narrative overview of English-language studies on the efficacy of secondary prevention and treatment interventions for crack (cocaine) abuse/dependence. Literature searches (1990-2014) using pertinent keywords were conducted in main scientific databases. Titles/abstracts were reviewed for relevance, and full studies were included in the review if involving a primary prevention/treatment intervention study comprising a substantive crack user sample. Intervention outcomes considered included drug use, health risks/status (e.g., HIV or sexual risks) and select social outcome indicators. Targeted (e.g., behavioral/community-based) prevention measures show mixed and short-term effects on crack use/HIV risk outcomes. Material (e.g., safer crack use kit distribution) interventions also document modest efficacy in risk reduction; empirical assessments of environmental (e.g., drug consumption facilities) for crack smokers are not available. Diverse psycho-social treatment (including contingency management) interventions for crack abuse/dependence show some positive but also limited/short-term efficacy, yet likely constitute best currently available treatment options. Ancillary treatments show little effects but are understudied. Despite ample studies, pharmaco-therapeutic/immunotherapy treatment agents have not produced convincing evidence; select agents may hold potential combined with personalized approaches and/or psycho-social strategies. No comprehensively effective 'gold-standard' prevention/treatment interventions for crack abuse exist; concerted research towards improved interventions is urgently needed.

In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between ‘chasing the dragon’ and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.

Background Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Methods Genetic information from four subject groups was collected: non-dependent opioid users ( NOD ) [n = 163]; opioid-dependent ( OD ) patients in methadone maintenance treatment ( MMT ) [n = 143]; opioid-dependent MMT -resistant patients in heroin-assisted treatment ( HAT ) [n = 138]; and healthy controls with no history of opioid use ( HC ) [n = 153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD ; HC vs. OD ( MMT + HAT ); and NOD vs. OD ( MMT + HAT ). Results Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor ( OPRD1) intronic SNP rs2236861 with non-dependent opioid use ( HC vs . NOD ) remained significant after correction for multiple testing (OR = 0.032; p corrected = 0.015). This SNP exhibited a significant gene–gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR = 5.24; p corrected = 0.041) ( HC vs . NOD) . Conclusions This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.

Background/Aims: Crack users in the Netherlands are an ageing and diverse population with longstanding criminal careers. Our aim was to assess factors associated with current criminal involvement and specialization in selling drugs, property crime and violence. Method: A sample of 1,039 frequent crack users was recruited in three major Dutch cities, combining respondent-driven sampling with random institutional sampling. Bivariate and logistic regression analyses were performed to find factors associated with current criminality. Results: A total of 431 participants (41.5%) had engaged in crime in the past 30 days, mostly selling drugs (68.9%), followed by property crimes (34.4%) and a few cases of violent crime (9.7%). Younger age, homelessness, heavier patterns of use and a more prolific criminal justice history were associated with current criminality. Those receiving welfare benefits tended to be more likely to specialize only in selling drugs as opposed to (also) property crimes. Conclusion: Reducing drug use among criminally involved crack users and addressing their housing conditions could have a significant impact on reducing drug-related crime. Welfare benefits might act as protective factor against committing property crimes but not against the selling of drugs.

Na de start in 1998 van een eerste fase in Amsterdam en Rotterdam is in de loop van 2000 in zes gemeenten in Nederland, te weten de genoemde en Den Haag, Groningen, Heerlen en Utrecht, het onderzoek naar de effectiviteit van heroine op medisch voorschrift van start gegaan. In dit artikel wordt ingegaan op de achtergrond en onderzoeksopzet van dit multicenter onderzoek en worden enkele eerste ervaringen beschreven.