Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care.

INTRODUCTION: Buprenorphine is well known in the treatment of opioid dependence. Despite a high safety profile and good tolerance buprenorphine has been subject to misuse and diversion. To reduce misuse the antagonist naloxone was added and the 4:1 combination of buprenorphine-naloxone was launched in Germany in March 2007. On the basis of the results from international clinical trials a non-interventional study was conducted to gather data on safety, effectiveness, retention and acceptability of buprenorphine-naloxone in the treatment of opioid dependent patients in routine care. METHODS: A nationwide multicentre 12-month prospective, non-interventional, post-marketing, surveillance study was carried out with 12 assessment points in N=384 opioid dependent patients currently in maintenance treatment from N=69 general practitioners, clinics and outpatient clinics in Germany. RESULTS: N=337 data sets were eligible for analysis. The rates of patients with serious and non-serious adverse events were low with 1.2% and 17.5%, respectively. No deaths occurred during the observational period and only one hospitalization was documented. Concomitant drug use decreased for all illicit substances. Mental health and quality of life measured with standardized self-assessment questionnaires improved significantly. The 12-month retention rate was 57.1%. Of the n=181 patients still in treatment at the end of the observation period, 96.7% continued treatment with buprenorphine-naloxone. CONCLUSION: The findings of the non-interventional study indicate high effectiveness and safety of buprenorphine-naloxone in the treatment of opioid dependence. The medication was well accepted by opioid dependent patients in long-term substitution treatment with substantial reductions of concomitant drug use and measurable improvement in quality of life.

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification between 1991 and 1997. The main hypothesis was that injecting illicit-heroin users would complete detoxification treatment less often than codeine- or methadone- substituted patients, and that methadone-substituted patients who had received more structured treatment would complete more often than codeine-substituted patients who did not receive any structured treatment beyond the prescription of codeine. We analysed a number of demographic and drug related variables as possible predictors. Our bivariate analyses confirmed our main hypothesis: 50.4% (OR: 1.8) of the methadone-substituted patients, 45.5% (OR: 1.5) of the codeine-substituted patients and 35.9% (OR: 1 comparison group) of the injecting illicit-heroin users completed the detoxification program (P=0.006). This finding remained significant even after correcting for a number of confounders. Using stepwise multiple logistic regression analyses, we found age, education, history of imprisonment, regular contact with a counsellor, currently being on probation and reported plans for participating in an abstinence treatment program to be significant predictors of completing detoxification treatment. Although the current analysis did not rule out differences in pharmacological effects as a contributing factor, the results are consistent with an interpretation of a dose-response association between psychosocial/psychotherapeutic support and detoxification outcome. More psychosocial/psychotherapeutic support leads to better detoxification treatment response.

Ofloxacin causes false-positive immunoassay results for urine opiates.

Abstract Immunoassay drug screening tests are usually used as a control during methadone maintenance programmes, to check cleanliness of drugs during detoxification treatment and abstinence programmes. False-positive results can have catastrophic consequences for the patient, as shown in the case report. False-positive results were reported for opioids following ofloxacin or rifampicin and for LSD following mucolytic. Since inpatient and outpatient units usually employ an urine quick test (immunoassay), positive results should be checked with gas chromatography/mass spectroscopy (GC-MS) or high pressure liquid chromatography (HPLC) before conclusions from the positive urine screening results can be drawn.

[Illegal drug users and risk factors for HIV and HCV infection]. / Ansprechbarkeit von Drogengebrauchern über Infektionsrisiken für HIV und HCV. Opioidabhängigkeit und HIV-Infektion.

Since the beginning of the HIV-epidemic, injection drug users (IDUs) have had a high risk of acquiring an infection with HIV. Chronic hepatitis C (HCV) is the most common infectious disease among IDUs. About 4 to 6 % of IDUs are HIV positive and more than 60 % are HCV positive. 90 % of HIV-positive IDUs are both HIV positive and HCV positive. Substitution treatment is the most effective prevention of HIV and HCV infection. Both HIV infection and chronic hepatitis C can be treated most successfully during substitution treatment.

Depression during therapy with interferon alpha--how long should an antidepressant treatment last?

Although depressive symptoms are well-known side effects of interferon alpha (IFNalpha), it is uncertain if these symptoms decline with the cessation of IFNalpha therapy. We report on a 47-year-old man who, apart from former drug abuse, never had suffered from a psychiatric disorder. However, he had a family history burdened with the suicide of his mother and his twin sister. After a depressive symptomatology during the IFNalpha therapy, which had been tolerably treated by mirtazapine, he committed a suicide attempt six months after the parallel termination of IFNalpha and antidepressant treatment. Two aspects of this case report should be emphasised. First, patients with an increased risk for psychiatric complications of interferon therapy must be followed closely for a depressive symptomatology and treated aggressively if symptoms arise. Second, this case report shows the relapse of depressive symptoms far beyond the end of the interferon treatment. If an antidepressant treatment is necessary during IFNalpha therapy this should not be stopped prematurely with the termination of the interferon medication.

[The "Qualified Detoxification Treatment of Drug Dependent Patients" Federal Model Project in a general hospital: concept, investments and clinical results]. / Das Bundesmodellprojekt "Qualifizierte Entzugsbehandlung Drogenabhängiger" an einem Krankenhaus der Maximalversorgung: Konzept, Inanspruchnahme und klinische Ergebnisse.

For 150,000 drug addicts 5,200 therapy slots are available in Germany. Until the late 80's detoxification treatment was only given a subordinate role in treating drug addicts. Due to the threat of the infectious disease AIDS and the increasing number of drug deaths new concepts were explored: In 1991 the first qualified detoxification ward for drug addicts was opened in a general hospital under the auspices of the Federal German model project "compact therapy for comprehensive drug treatment". Subsequently more than ten detoxification wards specifically for drug addicts were established in Bavaria alone, primarily in psychiatric county hospitals. Drug addicts are accepted into these qualified detoxification wards without preparation and precondition. Data of 1656 drug addicts were analysed who were treated between 1991 and 1996 at the ward described below: More than 70% come directly from the scene and 33% were accepted for the first time to inpatient detoxification treatment. Most of them are diagnosed with addictions to at least two substances (three substances 44%, two substances 24%). Many suffer from additional diseases: In 1079 out of 1656 a positive hepatitis-C serology was found, 22% had previously tried to commit suicide, 37% had to be treated in intensive-care because of life-threatening intoxication. Nevertheless, 58% of the drug addicts are transferred into continuing therapy after detoxification treatment or they continue to work in permanent employment. During detoxification treatment no patient died. Acceptance, additional diseases which can be diagnosed and treated best in a general hospital, and the high prevalence of addicted persons (at least 17-24%) in internal medical or surgical wards suggest that establishing qualified wards with special settings for addicts in general hospital is useful.

Treatment of hepatitis C infection in injection drug users.

Chronic hepatitis C is the most common infectious disease among injection drug users (IDUs). Because of the allegedly poor compliance of IDUs with treatment requirements and conditions, hepatologists recommend treatment only if former IDUs have spent 6 to 12 months drug free. The aim of this prospective study was to investigate whether opiate-dependent IDUs with chronic hepatitis C virus (HCV) infection can be treated successfully with interferon. Eligibility for the study meant IDUs had to be HCV-RNA positive by polymerase chain reaction. Subsequently 50 inpatients were enrolled during detoxification treatment. HCV treatment was started with interferon alfa-2a (through 1998) or a combined regimen consisting of interferon alfa-2a and ribavirin (begun in 1998). All patients were treated and supervised by specialized physicians in both hepatology and addiction medicine. The end point for this study was defined as a loss of detectable serum HCV RNA at week 24 after treatment. The rate of sustained virologic response was 36%. Sustained response rates were not significantly different for patients who relapsed and returned to treatment (53%), relapsed and did not return to treatment (24%), or did not relapse (40%; P >.05). During the 24 weeks after treatment, we were unable to detect any reinfection, even among patients who injected heroin during this period. This surprising result should be examined in further studies. In conclusion, HCV-infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa-2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine.

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. IV. Brain dysfunction during motor activation measured by EEG mapping.

In parts I-III of this series psychometric evidence was reported of a "psychotic motor syndrome" (PMS) in schizophrenic and endogenous depressed patients, which was not found in non-endogenous depressed or healthy persons. An attempt is reported to establish signs of brain dysfunction in these patient groups during motor activation, using a 16-channel EEG mapping system. "Resting" conditions after a special relaxation procedure were compared with simple and complex motor tasks (and music perception/reproduction; to be reported separately). Two measurements, at least 2 weeks apart, were obtained for each subject, in order to obtain information on the influence of drug treatment and/or psychopathological improvement on brain dysfunction. In all, 23 male and 25 female schizophrenics, 11 male and 18 female non-endogenous depressed patients (not actually mediated, i.e. drug naive or wash-out period of 1 week to 17 years), and 26 male and 37 female endogenous depressed patients (medicated with tri- or tetracyclic antidepressants and/or benzodiazepines; no lithium treatment) were compared with 22 male and 17 female control persons (i.e. total n = 179). Major findings were obtained in the delta and alpha frequency bands yielding signs of "diffuse hyperactivation" in schizophrenic and endogenous depressed patients as compared with the patterns found in healthy persons. However, since in the non-endogenous patients a (less marked) hyperactivation of various EEG parameters was also found, unspecific effects such as anxiety/arousal may have influenced the results in psychotic patients, which was to be explored further. Drug treatment tended to "normalize" the activation pattern both in schizophrenics and endogenous depressed patients. Viewing the findings on schizophrenics using neuroimaging methods [single photon emission computerized tomography-(SPECT), magnetic resonance imaging-(MRI), positron emission tomography-(PET)], these results suggest pathological brain organization connected to an impaired motor performance (evident peripherally as PMS) in schizophrenic and endogenous depressed patients. If it is possible to further "externally validate" (by SPECT/MRI/PET) EEG mapping data this method may exclusively offer the possibility of innocuous long-term follow up of brain dysfunction in psychotic patients ("brain function monitoring"). This could enable the early recognition (and early therapy) of negative symptoms. Finally, the EEG mapping findings provide further neurophysiological basis for the use of motor training programs in the additional therapy of psychiatric patients.

Myocardial Infarction associated with methadone and/or dihydrocodeine.

Chest pain and myocardial infarction occurring in young people with angiographically normal coronary arteries is well documented. Opiates have a cardioprotective effect and are used in acute heart attacks. We described a 22-year-old opioid addicted male patient who suffered a myocardial infarction following the consumption of methadone and dihydrocodeine.

[Malaria--state of the art. 2: Therapy and prevention of malaria]. / Malaria--State of the Art. Teil 2: Therapie und Prophylaxe der Malaria.

Suspected tropical malaria is an acute emergency. Immediate effective pharmacological treatment is of the essence. As in the case of prevention, various antimalarials are now available for treatment. Complicated tropical malaria requires treatment in hospital and intensive monitoring. The risk of infection and serious illness leading to a fatal outcome can be considerably reduced by suitable chemoprophylaxis or the use of stand-by medication for self-treatment, which, however, must be matched to resistance zones and the incidence of the four species of Plasmodium, in particular Plasmodium falciparum.

[Malaria--state of the art. I: Epidemiology, forms of malaria, diagnosis]. / Malaria--State of the Art. Teil 1: Epidemiologie, Malariaformen, Diagnostik.

Year for year, some 2.1 million people die of malaria worldwide. In Germany, about 1,000 people go down with the disease after visiting malarious areas, and up to 3% will die--mostly of tropical malaria. Decisive factors for mortality are age over 60 and delays in effective pharmacological therapy. It is essential that, in the presence of an appropriate history, malaria be suspected early on. The diagnosis can still be established using the "thick drop", or a blood smear stained with Pappenheim's stain, or Diff-Quick. In the event of a strong suspicion, the two methods should be applied every 8 hours for three days.

Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance.

BACKGROUND & AIMS: Acute hepatitis C virus infection accounts for approximately 20% of cases of acute hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for acute hepatitis C virus. METHODS: The diagnosis of acute hepatitis C virus in 60 patients was based on seroconversion to anti-hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of hepatitis C virus RNA in the first serum sample. RESULTS: Fifty-one of 60 (85%) patients presented with symptomatic acute hepatitis C virus. In the natural (untreated) course of acute symptomatic hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic hepatitis C. The start of antiviral therapy (interferon-alpha with or without ribavirin) beyond 3 months after the onset of acute hepatitis induced sustained viral clearance in 80% of treated patients. CONCLUSIONS: The management of acute hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic acute hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.