Peter Blanken

Heroin-assisted Treatment (HAT) a Decade Later: A Brief Update on Science and Politics

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.

Cue Exposure Therapy for the Treatment of Opiate Addiction: Results of a Randomized Controlled Clinical Trial

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.

Treatment of adolescents with a cannabis use disorder: Main findings of a randomized controlled trial comparing multidimensional family therapy and cognitive behavioral therapy in The Netherlands

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.

Outcome of long-term heroin-assisted treatment offered to chronic, treatment-resistant heroin addicts in the Netherlands.

AIMS To describe 4-year treatment retention and treatment response among chronic, treatment-resistant heroin-dependent patients offered long-term heroin-assisted treatment (HAT) in the Netherlands. DESIGN Observational cohort study. SETTING AND INTERVENTION Out-patient treatment in specialized heroin treatment centres in six cities in the Netherlands, with methadone plus injectable or inhalable heroin offered 7 days per week, three times per day. Prescription of methadone plus heroin was supplemented with individually tailored psychosocial and medical support. PARTICIPANTS Heroin-dependent patients who had responded positively to HAT in two randomized controlled trials and were eligible for long-term heroin-assisted treatment (n = 149). MEASUREMENTS Primary outcome measures were treatment retention after 4 years and treatment response on a dichotomous, multi-domain response index, comprising physical, mental and social health and illicit substance use. FINDINGS Four-year retention was 55.7% [95% confidence interval (CI): 47.6-63.8%]. TREATMENT Response was significantly better for patients continuing 4 years of HAT compared to patients who discontinued treatment: 90.4% versus 21.2% [difference 69.2%; odds ratio (OR) = 48.4, 95% CI: 17.6-159.1]. Continued HAT treatment was also associated with an increasing proportion of patients without health problems and who had stopped illicit drug and excessive alcohol use: from 12% after the first year to 25% after 4 years of HAT. CONCLUSIONS Long-term HAT is an effective treatment for chronic heroin addicts who have failed to benefit from methadone maintenance treatment. Four years of HAT is associated with stable physical, mental and social health and with absence of illicit heroin use and substantial reductions in cocaine use. HAT should be continued as long as there is no compelling reason to stop treatment.

Matching adolescents with a cannabis use disorder to multidimensional family therapy or cognitive behavioral therapy: Treatment effect moderators in a randomized controlled trial

BACKGROUND In a recent randomized controlled trial (Hendriks et al., 2011), multidimensional family therapy (MDFT) and cognitive behavioral therapy (CBT) were equally effective in reducing cannabis use in adolescents (13-18 years old) with a cannabis use disorder (n=109). In a secondary analysis of the trial data, we investigated which pretreatment patient characteristics differentially predicted treatment effect in MDFT and CBT, in order to generate hypotheses for future patient-treatment matching. METHODS The predictive value of twenty patient characteristics, in the area of demographic background, substance use, substance-related problems, delinquency, treatment history, psychopathology, family functioning and school or work related problems, was investigated in bivariate and subsequent multivariate linear regression analyses, with baseline to month 12 reductions in cannabis use days and smoked joints as dependent variables. RESULTS Older adolescents (17-18 years old) benefited considerably more from CBT, and younger adolescents considerably more from MDFT (p<0.01). Similarly, adolescents with a past year conduct or oppositional defiant disorder, and those with internalizing problems achieved considerably better results in MDFT, while those without these coexisting psychiatric problems benefited much more from CBT (p<0.01, and p=0.02, respectively). CONCLUSIONS The current study strongly suggests that age, disruptive behavior disorders and internalizing problems are important treatment effect moderators of MDFT and CBT in adolescents with a cannabis use disorder. If replicated, this finding suggests directions for future patient-treatment matching in adolescent substance abuse treatment.

Treatment of crack-cocaine dependence with topiramate: A randomized controlled feasibility trial in The Netherlands

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

Craving and illicit heroin use among patients in heroin-assisted treatment

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.

Cue exposure therapy for opiate dependent clients

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.

Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial

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.

Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence

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 Cloningers 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).