[Evaluation of the Lippstädter Benzo-Check as a Screening Tool for Side Effects of Long-term Use of Benzodiazepines and Z-drugs]. / Evaluation des Lippstädter Benzo-Checks als Screening-Instrument für Nebenwirkungen der Langzeiteinnahme von Benzodiazepinen und Z-Substanzen.

OBJECTIVE: The Lippstädter Benzo-Check is intended to motivate those affected by unwanted effects of Benzodiazepines and Z-drugs. This study serves as the first check whether the Lippstädter Benzo-Check adequately recorded the symptoms of longterm-use before the withdrawal and, on the other hand, a depressive control group without taking the corresponding drugs unremarkable values ​​achieved. METHODS: 101 inpatient withdrawal patients with dependency on Benzodiazepines or Z-drugs and 154 day clinic patients without benzodiazepines or Z-drugs completed the Lippstädter Benzo-Check at the beginning of treatment. The total score and a subscore "dependency" were compared between the two groups. RESULTS: The total score ​​of the Lippstädter Benzo-check in the two collectives differ highly significantly, nevertheless around half oft he depressed patients are in the lowest of three warning areas - "the symptoms you have specified probably come from the long-term use oft he medication".The items "sleep disorder", "stealth", "loss of effectiveness", "fixation on medication" and "extension oft he indication" can be combined into a subscore ("dependency score"). This achieves a high selectivity for a cut-off value of<5 points, since 100% of the day clinic patients and only 10% of the withdrawal patients are below it. CONCLUSIONS: The results of this first study using the Lippstädter Benzo-Check as a screening tool for undesirable consequences on benzodiazepines or Z-drugs are encouraging, despite methodological limitations and the need for further investigations.

Very Low Frequency of Drug Therapy of Alcohol Dependence in Germany - Analysis of Data of A Statutory Health Insurance.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

[Benzodiazepines and Z-Drugs - Analyses of Ambulatory Prescriptions from 2006 to 2015]. / Benzodiazepine und Z-Substanzen ­ Analyse der kassenärztlichen Verschreibungen von 2006 bis 2015.

OBJECTIVE: The majority of medication-dependent persons uses sedatives and hypnotics for many years. In this study we describe trends of benzodiazepine and z-drug prescriptions over a 10-years period. METHODS: Prescriptions from 2006 to 2015 (based on German statutory health insurances) from the North German Pharmacy Computing Centre (NARZ) were analysed for the Federal states Schleswig-Holstein, Hamburg, Lower Saxony and Bremen. Data were classified as appropriate (in accordance with the guideline) or inappropriate/risky prescription patterns. RESULTS: In a 10-years period 1.64 Million patients received benzodiazepine and/or z-drug prescriptions. Two thirds were women (65.3 %). More than half were 60 years or older. The percentage of patients with appropriate prescriptions (less than 2 months) increased from 51.7 % in 2006 to 60.2 % in 2015. The rate of inappropriate or risky prescription patterns which can be indicative of misuse or dependence dropped from 34.8 % in 2006 to 27.1 % in 2015. CONCLUSION: Over the past years the amount of inappropriate or risky benzodiazepine and z-drug prescriptions (which are not in accordance with the guideline) among patients with statutory health insurance is steadily decreasing. However, two fifths of the patients still received prescriptions for long-term intake or in higher doses. It remains unclear to what extent private prescriptions are used for inappropriate or long-term prescriptions of benzodiazepines and z-drugs.

The Prescription of Anticraving Medication and its Economic Consequences.

IMPORTANCE: According to recent studies, only a small proportion of alcoholics in the system for addiction treatment receive expedited treatment [Rehm et al.: Sucht 2014;60:93-105] and that those who are untreated are at risk of harmful and dependent alcohol consumption. This is associated with significantly negative effects on morbidity, mortality, and quality of life [Kraus et al.: Sucht 2010;56:337-347]. As a result, not only individuals and their environment suffer but there is also a health economic impact. OBJECTIVE: How often do patients with a primary or secondary diagnosis of alcohol dependence who have been discharged from inpatient treatment receive anticraving medication in the follow-up period of 6 months? DESIGN, SETTING, AND PARTICIPANTS: Based on data from a statutory health insurance in Germany, 12,958 patients were investigated regarding alcohol dependence, rates for readmission to hospital, and prescription of anticraving drugs. In addition, outpatient and inpatient treatment costs were calculated. Main Outcomes and Measures: There will be an examination of how often anticraving medications are prescribed and what the economic consequences are. RESULTS: Two hundred and eighty-eight (2.22%) patients received anticraving medication, 98 (0.76%) in the first 6 months after inpatient treatment. Fifty-nine of the 288 patients were monitored with a pre- and postcomparison over a 90-day period. Inpatient treatment fell from 0.83 times (±1.10) during the 3 months afterward to 0.79 (±1.01). On average, the duration of an inpatient stay before anticraving treatment (n = 29) was 17.34 days (±14.37), with an average cost of EUR 4,142.70 (±2,721.28). Among the anticraving treatment group, this fell to 14.03 days (±9.96) with an average cost of EUR 3,685.43 (±2,307.67). Overall, the average outpatient and inpatient treatment costs dropped from EUR 1,533.88 before treatment to EUR 1,462.76 after treatment. If this is extrapolated to the whole group, it leads to between EUR 921,500 and EUR 6.6 million saving for a health insurance company. CONCLUSION: Anticraving medications are hardly ever prescribed. Their routine use could reduce hospital readmission rates and save on health-care costs.

Problematic Medication With Benzodiazepines, "Z-drugs", and Opioid Analgesics.

BACKGROUND: An estimated 1.4 to 2.6 million people in German suffer from drug dependence. Most of them are long-term users of benzodiazepines (BZD), Z drugs (ZD), or opioid analgesics (OA). METHODS: This analysis is based on prescription data from patients of the national statutory health insurance system in the German federal states of Schleswig-Holstein, Hamburg, Bremen, and Lower Saxony. Drug-taking trends, duration, dosage, and long-term use of BZD, ZD, and OA in the years 2006 to 2015 are analyzed; prevalences are estimated for the years 2006 to 2016. RESULTS: In 2006, 7.7% of patients received at least one prescription for a BZD, ZD, or OA; in 2016, 7.0% did. Over the period of analysis, a marked drop was seen in prescriptions of BZD and a slight fall in prescriptions of ZD (2006: BZD 3.5%, ZS 1.1%; 2016: BZD 2.0%, ZS 0.8%), but there was also an increase in prescriptions of OA, from 4.2% to 4.9%. The number of defined daily doses (DDD) prescribed per year fell for both BZD and ZD. For OA, the number of DDD prescribed per year rose from 2006 to 2009 and decreased by a small amount in subsequent years. The proportions of BZD and ZD patients who had long-term prescriptions fell over time, while the corresponding percentage of OA patients rose. CONCLUSION: Nearly one-fifth of all prescriptions for BZD were long-term prescriptions for an entire year, in violation of the relevant guidelines. The rising prevalence of OA use was in the expected range in view of the aging population, but the number of prescriptions rose among younger patients as well. This trend toward more common treatment with opioid analgesics should be critically examined.

[Reasons for Long-Term Use of Benzodiazepines and Z-Drugs in Older Patients]. / Ursachen und Hintergründe der Langzeiteinnahme von Benzodiazepinen und Z-Substanzen bei älteren Patienten.

BACKGROUND: Long-term use of benzodiazepines (BZD) and Z-drugs is associated with the risk of developing dependency. Many older patients use these drugs for long durations, which is often associated with low-dose dependency without an increase in dose. AIM: The aim of this study is to investigate the reasons, symptoms, and side effects, as well as the prescription conditions among older patients who were prescribed BZD or Z-drugs within the last 12 months. METHODS: A 9-page questionnaire was sent to 4,000 patients of the AOK-NordWest, stratified according to age group (50-56 years;>65 years) and intake behavior (long-term use/ guideline incompatible; short-term use/ guideline compatible). Patients provided demographic data and indicated on a comprehensive list of BZD and Z-drugs, which substances they had used or were currently using. In addition, patients were asked about the reasons and underlying symptoms for taking these medications, possible side effects, and previous attempts to discontinue the medications. RESULTS: A total of 466 patients returned completed questionnaires (11.7%). A further 43 privately insured patients were recruited through pharmacies. 169 patients, mainly from the group with guideline-compatible prescriptions, indicated that they had never taken these medications. The remaining 340 patients were 68.5% female and the average age was 72.1 years. Compared to patients with guideline-compatible prescriptions, a greater proportion of patients with guideline-incompatible prescriptions were taking Z-drugs. The average daily dose (DDD) consumed was significantly higher than in those with guideline-compatible prescriptions, although on average both patient groups took low doses (<1 DDD) of the medication. In both groups, the main reason for taking BZD and Z-drugs was sleeping problems. CONCLUSIONS: Considering the recommendation that BZD and Z-drugs are to be taken only short-term for sleeping problems, the extent of insomnia indications is high. The low doses suggest a careful and controlled prescription behavior in both groups, with the majority of long-term consumers likely to have developed low-dose dependency. This is associated with only a limited need for intervention, since only few medication-dependent people underwent addiction treatment.

[The use of prescription drugs with dependence potential in Germany : A prospective analysis of prescriptions in the public healthcare system between 2006 and 2010]. / Der Gebrauch von Medikamenten mit Abhängigkeitspotenzial in Deutschland : Eine prospektive Analyse kassenärztlicher Verschreibungen der Jahre 2006 bis 2010.

BACKGROUND: In Germany, about 1.4 to 2.6 million people are dependent on prescription drugs, mainly benzodiazepine derivatives and opioid analgesics. Despite this large number of affected people, studies on prescription behaviour and drug intake are scarce. There are particularly few empirical findings available with regard to elderly people age 65 and over who are disproportionally affected by prescription drug abuse. METHODS: The North German Pharmacy Computing Centre (Norddeutsches Apothekenrechenzentrum, NARZ) collects the prescription data of about 11 million citizens and covers over 80% of drug pharmacies in North Germany. Based on the data from NARZ, we evaluate person-related prescriptions of benzodiazepines, Z­drugs and opioid analgesics. By means of incremental calculations, we determine the prevalence of prescription drug use, the long-term intake, the average daily dose of these medications and present this information as a five-year trend (2006-2010). RESULTS: In 2006, 10.6% of the members of public healthcare system were prescribed at least one of the medications under study. This proportion hardly changed within the five-year span. The share of patients with benzodiazepine prescription steadily decreased from 2006 (5.5%) to 2010 (5.1%), especially among elderly people. While the prevalence of Z­drug prescriptions remained the same at about 1%, there was a slight increase in prescriptions of opioid analgesics with 5.4% in 2006 to 5.7% in 2010. The proportion of patients with long-term prescriptions decreased with regard to benzodiazepines (from 17.0 to 12.8%) and Z­drugs (from 24.3 to 21.2%), but increased for opioid analgesics (from 19.2 to 21.2%). CONCLUSION: The analytical method used in this study is an innovative epidemiological approach to evaluate person-related register data over the course of several years. Establishing a monitoring system of prescription drugs with potential for dependence may allow for a quicker identification of trends and initiation of appropriate measures.

[Substance-abuse related emergencies--illegal drugs, part II]. / Psychosozialer Notfall--Substanzinduzierte Störungen durch illegale Drogen - Teil 2.

For the first time since the year 2000 the number of death due to substance abuse of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006). Emergency situations due to drug abuse are frequent, particular in big cities. They may be, however, difficult to diagnose and / or treat for an emergency physician on scene because of a lack of diagnostic tools, the local and personal surroundings, and the unknown number and nature of drugs. Many drug intoxications must be considered suicidal. On the other hand, drug intoxications may mask (other) life-threatening conditions. Emergency situations due to withdrawal offer the possibility to motivate patients to take advantage of specialist-guided abstinence programs.

[Substance-abuse related emergencies--illegal drugs, part I]. / Psychosozialer Notfall--Substanzinduzierte Störungen durch illegale Drogen--Teil 1.

For the first time since the year 2000 the number of death due to substance abuse of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006). Emergency situations due to drug abuse are frequent, particular in big cities. They may be, however, difficult to diagnose and/or treat for an emergency physician on scene because of a lack of diagnostic tools, the local and personal surroundings, and the unknown number and nature of drugs. Many drug intoxications must be considered suicidal. On the other hand, drug intoxications may mask (other) life-threatening conditions. Emergency situations due to withdrawal offer the possibility to motivate patients to take advantage of specialist-guided abstinence programs.

[Alcohol-related disorders in the preclinical medicine]. / Psychosozialer Notfall--Substanzinduzierte Störungen durch Alkohol.

Alcohol is the most frequently abused drug in Germany. Approximately 50.000 individuals die annually due to alcohol-related disorders. Emergency situations due to alcohol intoxications, abuse or dependence are frequent reasons for calls for emergency physicians and paramedics. Agitation, suicidal intent, trauma and a multitude of degenerative and other somatic disorders may further complicate diagnosis and treatment on scene. The motivation of patients to participate in withdrawal programs should be built and strengthened already in emergency medicine.

Objective and subjective efficacy as well as tolerability of olanzapine in the acute treatment of 120 patients with schizophrenia spectrum disorders.

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3+/-5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86-90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after > or =3 weeks of treatment) of > or =20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower > or =40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsychotic efficacy and tolerability.

Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study.

BACKGROUND: Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds. METHODS: After detoxification, 160 patients with alcoholism participated in a randomized, double-blind, placebo-controlled protocol. Patients received naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed weekly by interview, self-report, questionnaires, and laboratory screening. Time to first drink, time to relapse, and the cumulative abstinence time were the primary outcome measures. RESULTS: Naltrexone, acamprosate, and the combined medication were significantly more effective than placebo. Comparing the course of nonrelapse rates between naltrexone and acamprosate, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone. CONCLUSIONS: The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention.

Comparing the efficacy of atypical antipsychotics in open uncontrolled versus double-blind controlled trials in schizophrenia.

OBJECTIVE: Due to methodological reservations, open clinical trials investigating efficacy and tolerability of antipsychotic agents are often regarded with doubt. However, there are nearly no studies comparing findings of controlled double-blind with those of open trials. The aim of this study was to investigate whether results of open and double-blind approaches differ and thereby gain information about the validity of open trials. METHODS: After literature research, three atypical antipsychotic agents were identified for which at least three open and double-blind trials existed that met the inclusion criteria and from which either the reduction of the Brief Psychiatric Rating Scale (BPRS)- or Positive and Negative Symptom Scale (PANSS) scores or the response rate could be determined. RESULTS: There were no differences in the reduction of the BPRS- or PANSS scores or in the response rates for all three antipsychotic agents between open and double-blind trials. CONCLUSIONS: Although double-blind controlled studies are essential in the investigation of new compounds, results of methodologically well-performed open studies are valid and deserve more attention. Preceding open trials may help in the design of double-blind studies.