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Introduction: The first-line treatment for opioid dependence is opioid agonist treatment (OAT) with oral opioids. However, in some cases, treatment with intravenous diacetylmorphine (IV-DAM) is indicated. Research on neurocognitive impairments and treatment effects of OAT - particularly with IV-DAM - on neurocognitive functioning, is scarce. The current study is the first to investigate the neurocognitive performance of individuals on OAT with IV-DAM. Using a prospective study design with two timepoints of measurement, the first aim was to assess the nature and extent of neurocognitive functioning in individuals with opioid dependence by comparing participants' neurocognitive performance with normative data of the general population on admission to treatment (baseline) and after an initial three-month period of OAT (study end). The second aim was to examine whether and to what extent neurocognitive performance would improve after three months on OAT. The third aim was to investigate whether, and if so, to what extent the treatment method (IV-DAM vs. oral opioids) would lead to higher neurocognitive improvements at study end. Methods: Forty-seven opioid-dependent individuals (baseline; 33 individuals at study end) participated in this study (mean age: 34.3 years; 27.7% female). Participants underwent neuropsychological testing with a battery of 12 tests covering different neurocognitive domains, including attention, memory, and executive functions. Results: Compared to normative data, opioid-dependent individuals showed impairments in almost every test both at baseline and at study end. At baseline, neurocognitive performance did not differ between individuals receiving IV-DAM or oral opioids for OAT. Compared to baseline, the neurocognitive performance did neither improve nor deteriorate after three months of treatment with neither IV-DAM nor oral opioids. However, a trend towards improvement was found for the memory domain. Discussion: Given that neurocognitive impairments should be considered in treatment planning and therapeutic interventions. Since a reduced cognitive performance may affect both the treatment outcome and the therapeutic relationship unfavorably, specific neurocognitive training at the beginning of treatment should be considered.

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OBJECTIVES: Chronic diseases are often associated with cycling in and out of treatment. We used data of a large opioid substitution treatment case register to (1) identify associated factors and (2) integrate retention and readmission into a model of overall participation over subsequent treatment episodes of various groups. STUDY DESIGN AND SETTING: Data of all 9,407 patients undergoing 26,545 methadone or buprenorphine substitution treatment episodes between 1992 and 2012 in the canton of Zurich, Switzerland, were analyzed. We used extended survival analysis to estimate the duration of, and time between, treatment episodes, with the number of episodes, gender, nationality, administration route, age at onset of first regular heroin use, and provider type as independent variables. A similar analysis was applied to estimate overall participation (the probability of being in treatment at a given day after first entry independent of current number of treatment episode) and to test for group differences. RESULTS: The time between treatment episodes shortened with the increasing number of episodes. Retention slightly increased after the first episode and then shortened for later treatment episodes. Effect sizes were generally rather weak (odds ratio ≤ 1.47). Effects were usually equal for all episodes, and if changing, weakened for later episodes. CONCLUSION: The complex process of leaving and entering treatment as well as the daily probability of being in treatment independent of treatment episode can be predicted by comprehensible statistical models applied to patient-period data sets.

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BACKGROUND: We have sought to identify ethnic- and gender-specific differences in HIV prevalence among heroin users receiving opioid maintenance treatment in the canton of Zurich, Switzerland. METHODS: We used a generalized linear model (GEE) to analyze data from the anonymized case register for all opioid maintenance treatments in the canton of Zurich. Patients who received either methadone or buprenorphine between 1991 and 2012 (n=11,422) were evaluated for gender (male vs. female), ethnic background (Swiss vs. non-Swiss), and lifetime method of drug use (ever injector vs. non-injector). We addressed missing data by multiple imputation. RESULTS: The overall prevalence of HIV among patients declined substantially from 33.7% in 1991 to 10.6% in 2012 in the complete dataset. In the imputed datasets, the respective prevalence dropped from 32.8% in 1991 to 9.7% in 2012. Non-injectors had a four to five times lower risk ratio (RR) compared to the reference group, 'Swiss males who ever injected'. In addition, we found a significantly higher risk ratio of HIV prevalence among females who had ever injected; this was true both for the complete dataset and the imputed dataset (Swiss RR 1.18 CI 95% 1.04-1.34, non-Swiss RR 1.58 CI 95% 1.18-2.12). CONCLUSION: In this population, gender, ethnic background, and lifetime method of drug use influenced the risk of being HIV positive. Different access to treatment and different characteristics of risk exposure among certain subgroups might explain these findings. In particular, the higher risk for women who inject drugs-especially for those with an immigrant background-warrants additional research. Further exploration should identify what factors deter women from using available HIV-prevention measures and whether and how these measures can be better adapted to high-risk groups.

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OBJECTIVES: Several studies have reported prolonged QTc intervals in patients under methadone maintenance treatment, including development of torsade-de-pointes arrhythmia and death. It is still not clear why some patients develop critical QTc extensions while others do not. METHODS: ECG findings in a convenience sample of 210 methadone-maintained heroin-dependent patients, taking HCV-infection status and methadone dosage into account simultaneously by means of a multiple linear regression model with QTc-interval as the dependent variable. RESULTS: Prolonged QTc-time is associated with hepatitis C infections (p = 0.005) and higher doses of racemic methadone (p = 0.012). CONCLUSION: Infection with hepatitis C increases the likelihood of critical QTc prolongation in patients in methadone maintenance treatment.

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BACKGROUND: Dependent cocaine users consistently display cognitive deficits but cognitive performance of recreational cocaine users has rarely been investigated. AIMS: To examine whether cognitive performance is impaired in relatively pure recreational and dependent cocaine users. METHOD: The cognitive performance of recreational (n = 68) and dependent cocaine users (n = 30) was compared with the performance of stimulant-naive controls (n = 68) employing an extensive neuropsychological test battery. Moreover, the impact of attention-deficit hyperactivity disorder (ADHD) symptoms, craving and early age at onset was analysed. RESULTS: Dependent cocaine users display broad cognitive impairments in the domains of attention, working memory, declarative memory and executive functions. The performance of recreational cocaine users in all four domains was intermediate between that of controls and dependent users and they displayed significant deficits foremost in the domains of attention and working memory. In addition, ADHD symptoms, craving and age at onset were important modulators of cognitive function in cocaine users. CONCLUSIONS: Cognitive deficits occur at a recreational and non-dependent level of cocaine use. Cocaine use and ADHD seem to have mutually aggravating effects on cognitive impairment.

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Over the past years a growing research effort has investigated the relation between cannabis use and schizophrenia at a neurobiological, epidemiological and clinical level. A number of systematic reviews and meta analyses have summarized the available evidence in the field. Conversely the patient's perception of the link between cannabis use and psychosis has been under investigation. Since patient's beliefs and attitudes strongly correlate with adherence to all forms of treatment, we conducted a systematic PUBMED database search for any English and German-language articles published until January 2012 that addressed patient's perception of a cannabis psychosis link. Six studies including psychotic subjects met inclusion criteria yielding a total sample of 97. The vast majority of patients with either schizophrenia or a recent psychosis disagreed with a causal link between cannabis use and their mental illness. We qualitatively reviewed the explanatory models underlying their views, which were multi-factorial, psychological, social, biological, esoteric and irrational factors. Most patient's believed that the temporal sequence of events did not clearly indicate a causal relationship for them. They thus discarded the hypothesis of a causal link between cannabis use and psychosis. Despite the heterogeneity of the included studies, findings are comparable and support the robustness of this review. Limitations and implications for clinicians and psychosis research are discussed.

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INTRODUCTION: Stimulant medication improves hyperactivity, inattention, and impulsivity in both pediatric and adult populations with Attention Deficit Hyperactivity Disorder (ADHD). However, data regarding the optimal dosage in adults is still limited. CASE PRESENTATION: We report the case of a 38-year-old Caucasian patient who was diagnosed with Attention Deficit Hyperactivity Disorder when he was nine years old. He then received up to 10 mg methylphenidate (Ritalin®) and 20 mg sustained-release methylphenidate (Ritalin SR®) daily. When he was 13, his medication was changed to desipramine (Norpramin®), and both Ritalin® and Ritalin SR® were discontinued; and at age 18, when he developed obsessive-compulsive symptoms, his medication was changed to clomipramine (Anafranil®) 75 mg daily. Still suffering from inattention and hyperactivity, the patient began college when he was 19, but did not receive stimulant medication until three years later, when Ritalin® 60 mg daily was re-established. During the 14 months that followed, he began to use Ritalin® excessively, both orally and rectally, in dosages from 4800-6000 mg daily. Four years ago, he was referred to our outpatient service, where his Attention Deficit Hyperactivity Disorder was re-evaluated. At that point, the patient's daily Ritalin® dosage was reduced to 200 mg daily orally, but he still experienced pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage was raised again. The patient's plasma levels consistently remained between 60-187 nmol/l-within the recommended range-and signs of his obsessive-compulsive symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378 mg extended-release methylphenidate (Concerta®), his symptoms of Attention Deficit Hyperactivity Disorder have improved dramatically and no further use of methylphenidate has been recorded during the 24 months preceding this report. CONCLUSIONS: Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in this adult patient, who also manifested a co-occurring obsessive compulsive disorder, dramatically improved only after application of a higher-than-normal dose of methylphenidate. We therefore suggest that clinicians consider these findings in relation to their adherence to current therapeutic guidelines.

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INTRODUCTION AND AIMS: Risk factors for osteoporosis are prevalent in chronic heroin users who often start using opiates in their late teens. This study was the first to evaluate bone mineral density (BMD) in relatively young heroin-dependent patients on injectable heroin maintenance. DESIGN AND METHODS: Using cross-sectional design, BMD was assessed in a convenience sample of 19 patients (mean age ± SD = 33.9 ± 5.4; 13 men) prescribed injectable diacetylmorphine for heroin dependence. BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry. Substance use and menstrual history, psychopathology and risk factors for low BMD were assessed by questionnaire-based interviews. RESULTS: According to World Health Organisation criteria almost three-quarters (74%) of the sample had osteopenia (n = 11) or osteoporosis (n = 3) at one or more sites of measurement. All patients showed multiple risk factors for bone loss, with pack-years of tobacco use and years of heroin use reaching marginally significant associations with spine Z-scores. Moreover, BMD Z-scores correlated significantly negatively with increasing age at all sites, indicating that the older the patient, the greater the BMD deviation from an age-controlled population. DISCUSSION AND CONCLUSIONS: Prolonged heroin dependence appears to be associated with lower-than-normal bone mass already at early age and these individuals might be at greater risk for fracture with advancing age. The negative correlation of age-adjusted Z-scores with increasing age suggests factors other than age for low BMD in this population (e.g. smoking, heroin use). Prospective studies are warranted to determine the necessity for diagnostic and preventive measures.

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BACKGROUND: There has been a considerable amount of debate among the research community whether cannabis use may cause schizophrenia and whether cannabis use of patients with schizophrenia is associated with earlier and more frequent relapses. Considering that studies exploring patients' view on controversial topics have contributed to our understanding of important clinical issues, it is surprising how little these views have been explored to add to our understanding of the link between cannabis and psychosis. The present study was designed to elucidate whether patients with schizophrenia who use cannabis believe that its use has caused their schizophrenia and to explore these patients other beliefs and perceptions about the effects of the drug. METHODS: We recruited ten consecutive patients fulfilling criteria for paranoid schizophrenia and for a harmful use of/dependence from cannabis (ICD-10 F20.0 + F12.1 or F12.2) from the in- and outpatient clinic of the Psychiatric University Hospital Zurich. They were interviewed using qualitative methodology. Furthermore, information on amount, frequency, and effects of use was obtained. A grounded theory approach to data analysis was taken to evaluate findings. RESULTS: None of the patients described a causal link between the use of cannabis and their schizophrenia. Disease models included upbringing under difficult circumstances (5) or use of substances other than cannabis (e. g. hallucinogens, 3). Two patients gave other reasons. Four patients considered cannabis a therapeutic aid and reported that positive effects (reduction of anxiety and tension) prevailed over its possible disadvantages (exacerbation of positive symptoms). CONCLUSIONS: Patients with schizophrenia did not establish a causal link between schizophrenia and the use of cannabis. We suggest that clinicians consider our findings in their work with patients suffering from these co-occurring disorders. Withholding treatment or excluding patients from certain treatment settings like day-care facilities or in patient care because of their use of cannabis, may cause additional harm to this already heavily burdened patient group.

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INTRODUCTION AND AIMS: To explore the combined effects of street-level law enforcement and substitution treatment programs on drug-related mortality, taking into account prevalence of heroin use and changes in injecting behaviour. DESIGN AND METHODS: Time trend analysis using annual police reports and case register data of opioid substitution treatments in Switzerland, 1975-2007. RESULTS: Drug-related mortality increased during times of more intense street-level law enforcement [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.15-1.51], and the number of drug-related deaths predicted the number of heroin possession offences 2 years later (r = 0.97, P < 0.001). Substitution treatment had a protective effect on drug-related mortality (OR 0.23, 95% CI 0.18-0.30). Surprisingly, the number of drug-related deaths was substantially biased by an oscillation period of 14 years (OR 1.24, 95% CI 1.17-1.32). DISCUSSION AND CONCLUSIONS: Our analysis revealed that the amount of police resources allocated to law enforcement was determined rationally, however, on biased grounds and with untoward consequences. Substitution treatment of heroin users reduced drug-related mortality in the long run, but different factors masked its impact for several years. Therefore, the introduction-or the expansion-of opioid substitution treatment programs should not be promoted with the argument of an immediate reduction of drug-related deaths in a country.

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Some patients on steady-state methadone occasionally crave for extra opioids for different reasons (eg, cue-elicited craving, stress). This study examined the acute-on-chronic effects on heroin craving, mood, and opioid-like symptoms of a single, extra half-dose on top of the patient's prescribed daily methadone dosage. A randomized, double-blind, placebo-controlled, counterbalanced crossover design was used to test the safety of this practice and the hypotheses that extra methadone would reduce heroin craving and improve mood, with greater responses in lower-dose (20-60 mg/d) as compared with higher-dose patients (80-120 mg/d). Fourteen stabilized methadone-maintained volunteers of each dose group were examined predrug and postdrug on 2 separate days using a range of self-report measures (Heroin Craving Questionnaire, visual analogs, Befindlichkeits-Skala, Short Opiate Withdrawal Scale, and Opioid Agonist Scale). Additionally, patients' expectations and guesses regarding treatment were assessed predrug and postdrug, respectively. No adverse effects occurred after extra methadone. Participants could not reliably distinguish between extra methadone and placebo. Repeated-measures analyses of variance showed no effects of extra methadone on heroin craving and opioid agonist effects. However, extra methadone improved mood on the Befindlichkeits-Skala (F1/24 = 4.71, P = 0.04), with marginally greater effects in lower-dose patients ((F1/24 = 2.94, P = 0.099). A single 50% extra methadone dose is most likely safe in patients on stable methadone doses of 20 to 120 mg/d and may improve patients' mood. Extra methadone may constitute an important factor in the attractiveness of maintenance treatment and may enhance treatment outcome.

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There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in- or out-patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist.

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According to the so-called telescoping effect, there is a gender-specific course of alcohol dependence with women starting alcohol use later than men and having a faster development of harmful consequences. There are inconsistent data regarding a telescoping effect in opiate dependence. In each of six European centres, 100 opiate addicts were investigated by a structured interview (mainly the EuropASI and CIDI) at admission to various kinds of treatment (TREAT project). In a secondary analysis of the TREAT data, women and men were compared regarding age at onset of heroin use and the current severity of addiction. In addition, a comparison of female (n = 140) and male (n = 140) addicts matched for age and study centre were carried out. Eventually, multiple logistic and linear regressions were done with the interaction term of gender and time of regular consumption as predictor for the severity of dependence, besides, other sociodemographic variables. There was no difference between genders regarding the age at onset of regular heroin consumption. Up to 4 years of regular consumption, there are gender-specific differences in the course of opiate dependence, e.g. a faster progression of legal problems in men and social problems in women. There were no differences in the severity of dependence other than more economic problems for women. A telescoping effect could only partially be observed in this large sample of opiate addicts. A gender-specific course was limited to the first years of consumption, and included domains with a faster progression for men. It has to be assumed that opiate dependence is a rapidly developing disorder with early chronification. Afterwards, only individual courses with influences of the national treatment system were observed.

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BACKGROUND: Regional incidence trends in regular heroin use are important for assessing the effectiveness of drug policies and for forecasting potential future epidemics. METHODS: To estimate incidence trends we applied both the more traditional Reporting Delay Adjustment (RDA) method as well as the new and less data demanding General Inclusion Function (GIF) method. The latter describes the probability of an individual being in substitution treatment depending on time since the onset of heroin use. Data on year of birth, age at first regular heroin use and date of admission to and cessation of substitution treatment was available from 1997 to 2006 for 11 of the 26 regions (cantons) of Switzerland. For the remaining cantons, we used the number of patients in 5-year age group categories published in annual statistics between 1999 and 2006. RESULTS: Application of the RDA and GIF methods on data from the whole of Switzerland produced equivalent incidence trends. The GIF method revealed similar incidence trends in all of the Swiss cantons. Imputing a constant age of onset of 21 years resulted in almost equal trends to those obtained when real age of onset was used. The cantonal incidence estimates revealed that in the mid 80s there were high incidence rates in various regions distributed throughout all of the linguistic areas in Switzerland. During the following years these regional differences disappeared and the incidence of regular heroin use stabilized at a low level throughout the country. CONCLUSION: It has been demonstrated that even with incomplete data the GIF method allows to calculate accurate regional incidence trends.

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BACKGROUND: There still are concerns about unwanted effects of harm-reduction measures that may lead to an increasing number of new heroin users. Furthermore, it is thought that the admission of a substantial proportion of heroin users to methadone treatments reduces the demand on the heroin market and thus results in a lower price for street heroin. And finally, the intensity of police activity in the drug field may also affect prices for street heroin. METHODS: As incidence of regular heroin use over more than a decade is rarely known elsewhere, we examined the Zurich experience between 1980 and 2005 by triangulating published and unpublished data, concerning heroin price, heroin purity level, heroin seizures and drug offences. This time period encompasses the time before and after the introduction of low-threshold methadone treatment in 1991. RESULTS: We found a steep peak of heroin incidence in 1990. The street price of heroin already declined from 700 to 60 Swiss Francs during the 80s. The number of heroin consumptions possession offences reported by the police increased since 1991 and peaked in 1997, 2 years after the closure of the last open drug scene. CONCLUSION: The introduction of low-threshold methadone treatment has not resulted in lower heroin prices and the increased police activity during the 90s has not led to higher heroin prices, even though the higher police activity in the late 90s may have contributed to the prevention of a re-establishment of open drug scenes. In conclusion, we did not find a close relationship between street prices of heroin, police activity, and incidence of problematic heroin use.

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BACKGROUND: The intravenous administration of ketamine, an N-methyl-D-aspartate receptor antagonist, results in a great improvement of depression symptoms, but it is not clear for how long. This single-case trial was conducted to explore the duration of improvement and the effects of a second administration on the clinical outcome. METHODS: In an open label trial, a 55-year-old male patient with treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence received two intravenous infusions of 0.5 mg/kg ketamine over the course of 6 weeks. Depression severity was assessed by means of a weekly clinical interview, the 21-item Hamilton Depression Rating Scale (HDRS), and the 21-item Beck Depression Inventory (BDI). RESULTS: The first ketamine infusion lead to a pronounced improvement of symptoms, peaking on the second day post infusion (HDRS -56.6%, BDI -65.4%). Positive effects started fading by day 7, reaching baseline by day 35. The second infusion was less efficacious: HDRS and BDI were reduced by 43 and 35%, respectively, and returned to baseline by day 7. CONCLUSION: In this patient with a co-occurring substance use disorder, repeated administrations of ketamine produced positive results. Since the second application has been less efficacious, doses and schedule of administrations need to be further investigated.

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Several studies have found that symptom patterns of cannabis-using schizophrenia patients differ from those of nonusers. However, these investigations have mostly included patients treated with typical neuroleptics (TN). Since differing symptoms could also result from a TN-cannabis combination and might not be due to cannabis use per se, this study examined schizophrenia symptoms in a group of cannabis-using outpatients treated with atypical antipsychotics. Forty-two schizophrenia outpatients participated and were divided into three groups: cannabis abstainers, moderate users, and daily users. Patients with any substance use disorder other than cannabis abuse/dependence, or patients meeting criteria for schizotypal, schizoaffective, affective, anxiety, delusional, or personality disorders were excluded from the study. All patients completed a self-constructed questionnaire assessing demographic and drug use characteristics and were interviewed using the semistandardized Positive and Negative Syndrome Scale (PANSS). Cannabis use was assessed by self-declaration. No differences were found between the abstainers, the moderate, and the daily users on the PANSS scores. Thus, schizophrenia patients treated with atypical neuroleptics do not differ in symptom patterns whether using or not using cannabis. The study's limitations are noted.

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OBJECTIVE: The aim of the present study was to compare self-reported reasons for cannabis use in patients with schizophrenia with those of matched healthy controls. METHODS: Thirty-six stable outpatients with schizophrenia treated with atypical antipsychotics and 36 matched controls were included. They completed a questionnaire exploring 15 common reasons for use, established in other studies. results: Overall, patients more frequently agreed with the proposed reasons for use than controls. More specifically, patients with schizophrenia more often stated that they consumed cannabis to fight boredom and to ease social contacts. CONCLUSIONS: Stable schizophrenia outpatients treated with atypicals do not use cannabis in order to reduce side-effects of medication or symptoms of their disorder. Rather, they used cannabis to overcome a feeling of social exclusion. Therefore, enhancing social participation of cannabis-using patients might be an effective strategy for reducing consumption.

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