Rudolf Stohler

Double-blind randomized trial of buprenorphine and methadone in opiate dependence

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.

Incidence of heroin use in Zurich, Switzerland: a treatment case register analysis

BACKGROUND Switzerland has been criticised for its liberal drug policy, which could attract new users and lengthen periods of heroin addiction. We sought to estimate incidence trends and prevalence of problem heroin use in Switzerland. METHODS We obtained information about first year of regular heroin use from the case register of substitution treatments in the canton of Zurich for 7256 patients (76% of those treated between 1991 and March, 2005). We estimated the proportion of heroin users not yet in substitution treatment programmes using the conditional lag-time distribution. Cessation rate was the proportion of individuals leaving substitution treatment programmes and not re-entering within the subsequent 10 years. Overall prevalence of problematic heroin use was modelled as a function of incidence and cessation rate. FINDINGS Every second person began their first substitution treatment within 2 years of starting to use heroin regularly. Incidence of heroin use rose steeply, starting with about 80 people in 1975, culminating in 1990 with 850 new users, and declining substantially to about 150 users in 2002. Two-thirds of those who had left substitution treatment programmes re-entered within the next 10 years. The population of problematic heroin users declined by 4% a year. The cessation rate in Switzerland was low, and therefore, the prevalence rate declined slowly. Our prevalence model accords with data generated by different approaches. INTERPRETATION The harm reduction policy of Switzerland and its emphasis on the medicalisation of the heroin problem seems to have contributed to the image of heroin as unattractive for young people. Our model could enable the study of incidence trends across different countries and thus urgently needed assessments of the effect of different drug policies.

Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset

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.

Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression

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.

Reasons for cannabis use: patients with schizophrenia versus matched healthy controls.

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.

Rapid cortical hemoglobin deoxygenation after heroin and methadone injection in humans: a preliminary report.

The short-term effects of intravenous opioids (heroin 20-300 mg, methadone 30-180 mg) on cortical hemoglobin oxygenation were examined by near infrared spectroscopy in ten opioid-dependent subjects and were compared with the effects of saline in ten age-matched normal controls. Heroin and methadone produced a rapid and dramatic decrease in cortical hemoglobin oxygenation. Saline had no effects. Opioid-induced acute deoxygenation of cortical hemoglobin is most likely associated with respiratory depression. Thorough medical monitoring is strongly recommended in intravenous opioid maintenance treatments.

Safety of injectable opioid maintenance treatment for heroin dependence

BACKGROUND There is a growing debate about injectable opioid treatment programs in many Western countries. This is the first placebo-controlled study of the safety of injectable opioids in a controlled treatment setting. METHODS Twenty-five opioid-dependent patients on intravenous (IV) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo. Acute drug effects were recorded, focusing on electrocardiography, respiratory movements, arterial blood oxygen saturation, and electroencephalography (EEG). RESULTS After heroin injection, marked respiratory depression progressing to a Cheyne-Stokes pattern occurred. Peripheral arterial blood oxygenation decreased to 78.9 +/- 8.7% (mean +/- SD) ranging from 52%-90%. During hypoxia, 7 of the 16 subjects experienced intermittent and somewhat severe bradycardia. Five subjects exhibited paroxysmal EEG patterns. After methadone injection, respiratory depression was less pronounced than after heroin injection. No relevant bradycardia was noted. CONCLUSIONS Opioid doses commonly prescribed in IV opioid treatment induce marked respiratory and circulatory depression, as well as occasionally irregular paroxysmal EEG activity. Further studies are needed to optimize the clinical practice of IV opioid treatment to prevent serious complications. Moreover, the extent of the observed effects raises questions about the appropriateness of IV opioid treatment in the present form.

Estimating incidence trends in regular heroin use in 26 regions of Switzerland using methadone treatment data

BackgroundRegional incidence trends in regular heroin use are important for assessing the effectiveness of drug policies and for forecasting potential future epidemics.MethodsTo 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.ResultsApplication 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.ConclusionIt has been demonstrated that even with incomplete data the GIF method allows to calculate accurate regional incidence trends.

A Comparison of Heroin Chasers with Heroin Injectors in Switzerland1

In a cross-sectional multicentre study, we compared the characteristics of heroin chasers and heroin injectors. Subjects were 162 primarily opioid-dependent volunteers for whom either chasing (n = 85) or injecting (n = 77) was the principal route of heroin administration. Each subject was rated by means of the Swiss version of the European Addiction Severity Index. Additionally, subjects completed a questionnaire battery including the Severity of Dependence Scale, the Symptom Checklist SCL-90-R, a self-constructed peergroup questionnaire and a semantic differential list to assess the connotative meaning of heroin chasers and injectors. The heroin injectors were older and more likely to use one or more other drugs besides heroin than the chasers. They had longer heroin-using careers, a longer duration of detention and a higher prevalence of some type of hepatitis. In conclusion, the differences between chasers and injectors were rather related to a longer history of heroin use than to the route of heroin administration.

Low-threshold methadone treatment, heroin price, police activity and incidence of heroin use: The Zurich experience

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.