RESUMO
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.
Assuntos
Comportamento Aditivo/psicologia , Saúde Mental/normas , Psicoterapia/métodos , Aliança Terapêutica , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Dextroanfetamina/administração & dosagem , Dependência de Heroína/reabilitação , Administração Oral , Adulto , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacocinética , Cromatografia Líquida , Estudos de Coortes , Preparações de Ação Retardada , Dextroanfetamina/efeitos adversos , Dextroanfetamina/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Cocaína Crack , Dextroanfetamina/administração & dosagem , Administração Oral , Estimulantes do Sistema Nervoso Central/efeitos adversos , Doença Crônica , Preparações de Ação Retardada , Dextroanfetamina/efeitos adversos , Método Duplo-Cego , Feminino , Dependência de Heroína/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Resultado do TratamentoRESUMO
BACKGROUND: Family therapy and family-based treatment has been commonly applied in children and adolescents in mental health care and has been proven to be effective. There is an increased interest in economic evaluations of these, often expensive, interventions. The aim of this systematic review is to summarize and evaluate the evidence on cost-effectiveness of family/family-based therapy for externalizing disorders, substance use disorders and delinquency. METHODS: A systematic literature search was performed in PubMed, Education Resource information Centre (ERIC), Psycinfo and Cochrane reviews including studies conducted after 1990 and before the first of August of 2013. Full economic evaluations investigating family/family-based interventions for adolescents between 10 and 20 years treated for substance use disorders, delinquency or externalizing disorders were included. RESULTS: Seven hundred thirty-one articles met the search criteria and 51 studies were initially selected. The final selection resulted in the inclusion of 11 studies. The quality of these studies was assessed. Within the identified studies, there was great variation in the specific type of family/family-based interventions and disorders. According to the outcomes of the checklists, the overall quality of the economic evaluations was low. Results varied by study. Due to the variations in setting, design and outcome it was not feasible to pool results using a meta-analysis. CONCLUSIONS: The quality of the identified economic evaluations of family/family-based therapy for treatment of externalizing disorders, adolescent substance use disorders and delinquency was insufficient to determine the cost-effectiveness. Although commonly applied, family/family-based therapy is costly and more research of higher quality is needed.
Assuntos
Comportamento do Adolescente/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/economia , Terapia Familiar/economia , Delinquência Juvenil/psicologia , Transtornos Relacionados ao Uso de Substâncias/economia , Adolescente , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/terapia , Análise Custo-Benefício , Humanos , Delinquência Juvenil/economia , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
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.
Assuntos
Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dextroanfetamina/uso terapêutico , Dependência de Heroína/complicações , Transtornos Relacionados ao Uso de Opioides/complicações , Adulto , Preparações de Ação Retardada/uso terapêutico , Dextroanfetamina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Países Baixos , Resultado do TratamentoRESUMO
BACKGROUND: Electronic health (eHealth) programs are often based on protocols developed for the original face-to-face therapies. However, in practice, therapists and patients may not always follow the original therapy protocols. This form of personalization may also interfere with the intended implementation and effects of eHealth interventions if designers do not take these practices into account. OBJECTIVE: The aim of this explorative study was to gain insights into the personalization practices of therapists and patients using cognitive behavioral therapy, one of the most commonly applied types of psychotherapy, in a youth addiction care center as a case context. METHODS: Focus group discussions were conducted asking therapists and patients to estimate the extent to which a therapy protocol was followed and about the type and reasons for personalization of a given therapy protocol. A total of 7 focus group sessions were organized involving therapists and patients. We used a commonly applied protocol for cognitive behavioral therapy as a therapy protocol example in youth mental health care. The first focus group discussions aimed at assessing the extent to which patients (N=5) or therapists (N=6) adapted the protocol. The second focus group discussions aimed at estimating the extent to which the therapy protocol is applied and personalized based on findings from the first focus groups to gain further qualitative insight into the reasons for personalization with groups of therapists and patients together (N=7). Qualitative data were analyzed using thematic analysis. RESULTS: Therapists used the protocol as a "toolbox" comprising different therapy tools, and personalized the protocol to enhance the therapeutic alliance and based on their therapy-provision experiences. Therapists estimated that they strictly follow 48% of the protocol, adapt 30%, and replace 22% by other nonprotocol therapeutic components. Patients personalized their own therapy to conform the assignments to their daily lives and routines, and to reduce their levels of stress and worry. Patients estimated that 29% of the provided therapy had been strictly followed by the therapist, 48% had been adjusted, and 23% had been replaced by other nonprotocol therapeutic components. CONCLUSIONS: A standard cognitive behavioral therapy protocol is not strictly and fully applied but is mainly personalized. Based on these results, the following recommendations for eHealth designers are proposed to enhance alignment of eHealth to therapeutic practice and implementation: (1) study and copy at least the applied parts of a protocol, (2) co-design eHealth with therapists and patients so they can allocate the components that should be open for user customization, and (3) investigate if components of the therapy protocol that are not applied should remain part of the eHealth applied. To best generate this information, we suggest that eHealth designers should collaborate with therapists, patients, protocol developers, and mental health care managers during the development process.
RESUMO
OBJECTIVES: Using Ecological Momentary Assessment we aimed to describe the time course of temptation episodes in alcohol-dependent outpatients in a real-life setting. We also examined whether affective and motivational variables were cross-sectionally and prospectively associated with temptation episodes. Additionally, we tested whether outpatients who drank against treatment goals (i.e., "lapsers") differed in craving, affect, and motivation from abstainers. METHODS: Participants were 43 alcohol-dependent outpatients (13 female). Using personal digital assistants (PDAs), patients were signaled to complete three random assessments per day for 4 weeks. They were also instructed to complete a temptation assessment whenever they experienced the temptation to drink alcohol. RESULTS: The number of temptation assessments declined over time and did not differ between lapsers and abstainers. Overall, craving was generally higher in lapsers (nâ¯=â¯14) than abstainers (nâ¯=â¯27). In lapsers, but not abstainers, abstinence motivation was lower at temptation assessments vs. random assessments. Across all patients, negative affect was prospectively associated with entry of temptation assessments later the same day. There were no significant effects for positive affect. CONCLUSIONS: In alcohol-dependent outpatients attempting to remain abstinent, negative affect is cross-sectionally associated with entry of temptation assessments. There is more evidence that negative affect precipitates temptations than vice versa. Professionals should be watchful of outpatients who report generally high levels of craving, and who report more negative affect and lower abstinence motivation, when tempted.
Assuntos
Afeto , Abstinência de Álcool/psicologia , Alcoolismo/psicologia , Motivação , Pacientes Ambulatoriais/psicologia , Adulto , Fissura , Avaliação Momentânea Ecológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: To evaluate whether rivastigmine, an achetylcholinesterase inhibitor (AChEl), may be effective in restoring memory in Wernicke-Korsakoff's syndrome (WKS). METHODS: Five patients treated with rivastigmine for a period of 6 months were compared with five matched control patients, who received 6 months' conventional treatment, but without rivastigmine. Memory tests were administered at baseline and after 6 months. RESULTS: Slight improvements were observed in both rivastigmine and control patients, but no significant differences in improvements were found between the study groups. CONCLUSION: Treatment with rivastigmine may not be effective in restoring memory in WKS patients.
Assuntos
Síndrome de Korsakoff/tratamento farmacológico , Síndrome de Korsakoff/psicologia , Fenilcarbamatos/uso terapêutico , Adulto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/psicologia , Esquema de Medicação , Humanos , Síndrome de Korsakoff/complicações , Masculino , Transtornos da Memória/complicações , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , RivastigminaRESUMO
AIMS: Previous studies have shown that abstinent heroin addicts exhibit an attentional bias to heroin-related stimuli. It has been suggested that attentional bias may represent a vulnerability to relapse into drug use. In the present study, the predictive value of pre-treatment attentional bias on relapse was examined in a population of abstinent heroin addicts. Further, the effect of cue exposure therapy (CET) on attentional bias was studied. DESIGN: Participants were assigned randomly to receive nine sessions of CET or placebo psychotherapy. SETTING: An in-patient drug abuse treatment setting. PARTICIPANTS: Abstinent heroin-dependent patients. MEASUREMENTS: Participants completed the emotional Stroop task both before and after completing treatment. FINDINGS: Pre-treatment attentional bias predicted relapse at 3-month follow-up, even when controlling for self-reported cravings at the test session. Further, attentional bias was reduced in both groups after therapy, independent of treatment condition. CONCLUSIONS: Attentional bias may tap an important component of drug dependence as it is a predictor of opiate relapse. However, CET does not specifically reduce attentional bias.
Assuntos
Atenção , Dependência de Heroína/psicologia , Sinais (Psicologia) , Feminino , Dependência de Heroína/reabilitação , Humanos , Masculino , Países Baixos , Recidiva , Risco , Estresse Psicológico/etiologiaRESUMO
A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to creatinine clearance. After heroin administration, the reaction time was significantly prolonged with 28+/-5.3 msec. in injecting and 13+/-4.9 msec. in inhaling patients. Cardiovascular changes were only mild after heroin administration. Craving-scores declined immediately after heroin administration in both administration groups. Subjective heroin effect was rated more positively in heroin inhaling than in injecting patients, despite the lower C(max) levels following heroin inhalation. In both groups, in this blinded study heroin dose increments were more appreciated than dose reductions. Increments of 50% of the regular heroin dose did not cause any serious side effect.
Assuntos
Analgésicos Opioides/farmacocinética , Heroína/farmacocinética , Transtornos Relacionados ao Uso de Opioides/metabolismo , Administração por Inalação , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Heroína/administração & dosagem , Heroína/uso terapêutico , Humanos , Injeções Intravenosas , Masculino , Metadona/farmacocinética , Metadona/uso terapêutico , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/psicologia , Transtornos Relacionados ao Uso de Opioides/reabilitação , Tempo de Reação/efeitos dos fármacosRESUMO
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.
Assuntos
Atenção/efeitos dos fármacos , Viés de Atenção/efeitos dos fármacos , Compostos Benzidrílicos/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína Crack/efeitos adversos , Comportamento Impulsivo/efeitos dos fármacos , Comportamento Aditivo/tratamento farmacológico , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Nootrópicos/uso terapêutico , Teste de Stroop , Resultado do TratamentoRESUMO
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<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant. CONCLUSIONS: Contingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use. The trial has been registered in The Netherlands National Trial Register under clinical trial registration number NTR4728.
Assuntos
Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Dependência de Heroína/tratamento farmacológico , Heroína/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Países Baixos , Fatores de Tempo , Resultado do TratamentoRESUMO
In preparation for a trial on co-prescription of inhalable heroin and methadone, two methods for inhalation of heroin/caffeine tablets were compared: the commonly used method of 'chasing the dragon' and a standardised procedure for inhalation of volatilised heroin, using a heating device. Five male addicts inhaled a tablet of smokable heroin daily for 5 days, alternating the inhalation method. Plasma concentrations of heroin, 6-acetylmorphine, morphine and morphine-3- and -6-glucuronide were determined using a liquid chromatography method with tandem mass spectrometric detection. The exposure to heroin and its metabolites (expressed as areas under the concentration-time curve) was significantly lower after smoking via the heating device than after 'chasing the dragon': heroin 80% and 6-acetylmorphine 73% lower (p < 0.05). Maximal concentrations of heroin and 6-acetylmorphine were also 80% and 70% lower (p < 0.05) after using the heating device. 'Chasing the dragon' is a more efficient inhalation method than inhalation via the heating device.
Assuntos
Heroína/administração & dosagem , Heroína/farmacocinética , Entorpecentes/administração & dosagem , Entorpecentes/farmacocinética , Administração por Inalação , Adulto , Cafeína/administração & dosagem , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Meia-Vida , Dependência de Heroína/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , FumaçaRESUMO
AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data. SETTING: Methadone maintenance programmes and heroin treatment centres in six cities in the Netherlands. PARTICIPANTS: Four hundred and thirty heroin addicts. INTERVENTION: Methadone plus injectable heroin or methadone plus inhalable heroin compared to methadone alone prescribed over 12 months: heroin maximum 1000 mg per day, methadone maximum 150 mg per day. MAIN OUTCOME MEASURE: Dichotomous, multi-domain response index, including validated indicators of physical health, mental status and social functioning. FINDINGS: Data of the inhalable and injectable heroin trials were pooled. Intention-to-treat analysis showed that treatment with medically prescribed heroin plus methadone was significantly more effective (51.8% response) than standard methadone maintenance treatment (28.7%) (95% CI of response difference: 14.1-32.2%). Multivariate logistic regression analyses showed that only one of all baseline characteristics was predictive of a differential treatment effect: patients who had previously participated in abstinence-orientated treatment responded significantly better to heroin-assisted treatment than to methadone treatment (61% versus 24%), while patients without experience in abstinence-orientated treatment did equally well in heroin-assisted or methadone maintenance treatment (39% and 38%, respectively). CONCLUSIONS: The effect of heroin-assisted treatment is not dependent on clinical characteristics, with the exception of previous abstinence-orientated treatment: medical prescription of heroin is most effective for those patients who have previously participated in abstinence-orientated treatment.
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Dependência de Heroína/reabilitação , Heroína/administração & dosagem , Metadona/administração & dosagem , Entorpecentes/administração & dosagem , Administração por Inalação , Adulto , Resistência a Medicamentos , Feminino , Humanos , Injeções , Modelos Logísticos , Masculino , Países Baixos , Cooperação do Paciente , Análise de RegressãoRESUMO
The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.
Assuntos
Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Heroína/farmacocinética , Entorpecentes/farmacocinética , Teobromina/farmacocinética , Teofilina/farmacocinética , Administração por Inalação , Administração Oral , Disponibilidade Biológica , Combinação de Medicamentos , Interações Medicamentosas , Meia-Vida , Dependência de Heroína/tratamento farmacológico , Humanos , Injeções Intravenosas , Metadona/farmacologia , PopulaçãoRESUMO
A low association between self-reported craving and physiological measures of craving is often found. Social desirability might influence this relation between subjective and physiological reactivity. Subjects were seventy-six in-patient abstinent heroin abusers. Social desirability, general craving scores and difference scores of physiological and subjective heroin craving, measured after exposure to a neutral and heroin cue were assessed. Cue reactivity, both subjective and physiological was found to be enhanced after exposure to a heroin-related cue. In line with earlier studies, a modest relation was found between subjective and physiological cue reactivity. Contrary to earlier research, however, high social desirability scores were associated with lower craving scores, but not with physiological scores. It can be concluded that, among other subject-related variables, social desirability influences self-reported craving but does not influence physiological reactivity in a clinical population. No significant moderation effect of social desirability on the relation between subjective and physiological reactivity was found.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Dependência de Heroína , Desejabilidade Social , Adulto , Sinais (Psicologia) , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etnologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Etnicidade , Feminino , Dependência de Heroína/diagnóstico , Dependência de Heroína/etnologia , Dependência de Heroína/psicologia , Humanos , Masculino , Marrocos/etnologia , Países Baixos/epidemiologia , Inquéritos e QuestionáriosRESUMO
RATIONALE: Recent studies provide evidence for specific aspects of cue processing in addictive disorders. OBJECTIVE: The present study employs event related potentials (ERPs) to investigate heroin related visual information processing. METHODS: Neutral and heroin related pictures were presented to 19 male abstinent heroin dependent patients and 14 male healthy controls. RESULTS: Patients exhibited larger slow positive wave (SPW) components of the ERP on heroin related pictures than on neutral pictures. Within healthy control subjects there was no difference on the SPW between neutral and heroin pictures. Within heroin dependent patients, mean SPW response to heroin pictures was correlated with post-experiment craving. CONCLUSION: This study provides neurophysiological evidence that information processing of drug-related information is abnormal in heroin dependent patients. The results provide further evidence for the cognitive and neurobiological accounts of substance dependence such as the incentive-sensitization theory.
Assuntos
Transtornos Cognitivos/etiologia , Sinais (Psicologia) , Dependência de Heroína/fisiopatologia , Processos Mentais , Comportamento Aditivo , Eletroencefalografia , Eletroculografia , Potenciais Evocados Visuais/fisiologia , Heroína/farmacologia , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologiaRESUMO
RATIONALE: Motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. OBJECTIVE: The present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional system is involved employing event-related potential (ERP) measurements. METHODS: Cocaine-addicted subjects and healthy controls were exposed to neutral and cocaine-related pictures whilst ERPs were recorded simultaneously over frontal, parietal and midline sites. RESULTS: Patients exhibited ERP amplitude discrepancies between neutral and cocaine-related pictures for N300, late slow positive wave (LSPW) and sustained slow positive wave (SSPW), whilst this effect was absent in control subjects. Differences in neutral and cocaine cue-evoked ERP waves were also found at left frontal sites for LSPW and SSPW in the patient group only. No group-specific cue-evoked ERP amplitudes were observed at parietal and midline sites. CONCLUSION: The findings confirm the assumption that cocaine cues induce motivational relevance in cocaine-dependent individuals. It is possible that exposure to cocaine cues triggers an appetitive emotional system since left frontal sites are assumed to be involved in processing positive emotional-laden stimuli. The present study provides evidence that the sensitivity of ERP correlates for cocaine cues may be an indicator of motivational and emotional processes in drug-dependent individuals.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína , Sinais (Psicologia) , Potenciais Evocados/fisiologia , Motivação , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Transtornos Relacionados ao Uso de Cocaína/psicologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Drug and alcohol dependence are associated with enhanced attention for drug-related stimuli. This cognitive processing bias has been suggested to be related to craving and to represent one of the core mechanisms of addition. The present study tests the hypothesis that enhanced attention for heroin cues is mediated by the dopaminergic system using haloperidol as dopamine antagonist. In a double blind, randomized crossover design, 17 detoxified heroin dependent patients received a single oral dose of haloperidol 2 mg and placebo. Patients performed an Emotional Stroop Task to assess the cognitive processing of drug cues under both conditions. In addition, self-reported craving was assessed. In the haloperidol condition, patients performed better on the Emotional Stroop Task than in the placebo condition. However, no effect of haloperidol on subjective craving was found. These findings provide preliminary indications that attentional bias in heroin dependent humans is mediated by dopaminergic mechanisms.