The problems of long-term treatment with benzodiazepines and related substances.

BACKGROUND: Benzodiazepine abuse and dependence have been recognized and widely discussed for more than 40 years. With more than 230 million daily doses prescribed in Germany per year, the burden of reimbursement on the statutory health insurance carriers is high, albeit with a slight decline from year to year. At present, about 50% of all prescriptions in Germany are issued privately, even for patients who have statutory health insurance. METHODS: We selectively review the literature on the epidemiology and treatment of benzodiazepine dependence and abuse in Germany. RESULTS: Estimates of the number of benzodiazepine-dependent persons in Germany range from 128 000 to 1.6 million. Most estimates take no account of the large number of private prescriptions (i.e., those that are not reimbursed by the statutory health insurance scheme), while many exclude prescriptions for elderly persons, for whom these drugs are frequently prescribed. For the outpatient treatment of benzodiazepine withdrawal, it is recommended that the drug should first be switched to an equivalent dose of another benzodiazepine with an intermediate or long-acting effect; the dose should then, in general, be reduced weekly. In case of consumption of a high dose (≥ 20 mg diazepam equivalent), hospitalization and the additional administration of carbamazepine or valproic acid are recommended. Flumazenil treatment can improve with - drawal symptoms and leads to higher abstinence rates. Antidepressants should be given only if the patient is depressed. The dependence potential of nonbenzodiazepine drugs such as zolpidem and zopiclon must also be borne in mind. CONCLUSION: Benzodiazepines are generally highly effective when first given, but they should generally be given only for strict indications and for a limited time. If these drugs still need to be given beyond the short term, timely referral to a specialist is indicated, and possibly also contact with the addiction aid system.

Comparison of anti-diabetic drug prescribing in children and adolescents in seven European countries.

AIMS: The aim of this study was to compare the prevalence of diabetes in children across seven European countries, when using prescribing of anti-diabetics as a proxy for diabetes. A secondary aim was to assess the potential for collaboration between countries using different databases in diabetes research. METHODS: Data were obtained from population-based clinical databases in seven European countries. The study population comprised children aged 0-18 years. Prescriptions were categorized using the Anatomic Therapeutic Chemical (ATC) classification. The one-year user prevalence in 2008 was calculated for each country and stratified by age and sex. RESULTS: We studied a total of 5.8 million children and adolescents. The prevalence of insulin prescribing varied between 1.1 and 3.5 per 1000 population, being highest in Sweden and lowest in Italy. In all countries, novel insulin analogues were the most commonly used insulins. The prevalence of oral anti-diabetic prescribing ranged from 0.08 per 1000 individuals in Sweden and Germany to 0.21 per 1000 population in the UK. Overall, the absolute number of oral anti-diabetic users was very low. CONCLUSION: This study shows that there is a varying frequency of type 1 diabetes in children and adolescents across Europe. We also demonstrated that it is possible to obtain similar information from different clinical databases within Europe, which would allow continuous monitoring of type 1 diabetes. Owing to the lack of indications in most of the databases, this approach is less suitable for type 2 diabetes.

Off-label use of prescription drugs in childhood and adolescence: an analysis of prescription patterns in Germany.

BACKGROUND: Not all drugs prescribed for children and adolescents are certified for use in these age groups. The present study describes the extent of off-label prescriptions in the outpatient sector and identifies deficits in the quality of product information. METHODS: This analysis is based on patient-specific but pseudonymized drug prescription data for approximately 289,000 0- to 16-year-old members of the Gmünder Ersatzkasse, a German statutory health insurance provider, in the year 2002. For each substance prescribed, information regarding the youngest certified age group was derived from the product data. RESULTS: Of the 1,429,981 prescribed drug packages (726 active substances), 87.4% (66.1% of active substances) were prescribed in accordance with their license and 3.2% (15.7% of active substances) were prescribed off-label. For 9.4% of prescriptions (18.2% of active substances) the licensing status could not be established. For neonates and infants the proportion of licensed prescriptions was below average, at 42.5% and 82.8% of the prescribed packages (20.0% and 38.6% of active substances) respectively. After infancy, prescriptions were predominantly in accordance with licensed use. Deficits were seen in the indication groups "alimentary tract and metabolism," "respiratory system," "dermatologicals," and "sensory organs." CONCLUSIONS: The methodology enables characterization of off-label prescription and identification of fields where further research is needed. With regard to the EU regulation on medicinal products for pediatric use, this could assume increasing importance and contribute to the development of appropriate and safe medicines for children.

Pharmaceutical care for migraine and headache patients: a community-based, randomized intervention.

BACKGROUND: Despite the high prevalence of headache and migraine in the general population, many people do not receive adequate medical attention and treatment. OBJECTIVE: To evaluate the effects of pharmaceutical care (defined as intensified structured counseling between patient and pharmacist, including the use of drug databases), for patients with headache or migraine, on both clinical and psychological endpoints. METHODS: A prospective, randomized, controlled intervention study was conducted using pharmacies in Northern Germany. A total of 112 pharmacies (26% of all pharmacies in the study region) recruited 410 patients with headaches. Pharmacies were randomly assigned to an intervention or control group. Patients were interviewed by telephone prior to the intervention and again after 4 months. Primary endpoints were number of days with headache, number and severity of headaches, self-efficacy, and the patients' perceptions of their health-related quality of life. RESULTS: Each pharmacy treated an average of 4.6 patients (total time effort 9 h). The intervention group consisted of 201 patients who received pharmaceutical care, whereas the control group comprised 209 patients who received standard counseling. In both groups, the number of headache attacks and intensity of pain in treated headache attacks did not change significantly between the first and second interviews. However, a statistically significant improvement in mental health and self-efficacy was shown in the intervention group. Intensity of pain in untreated headache attacks and the number of days with headache decreased in both groups. Most participants described this intervention as helpful and effective and 90% reported that they would recommend pharmaceutical care to other patients with headache. CONCLUSIONS: A short-term pharmaceutical care intervention improved patients' mental health and self-efficacy, although it did not significantly change the number and severity of headaches. The increase in self-efficacy and mental health associated with pharmaceutical care may be instrumental in improving long-term pharmacotherapy of patients with migraine and headache. To fully assess the effects of pharmaceutical care, a longer study may be required.

A three-country comparison of psychotropic medication prevalence in youth.

BACKGROUND: The study aims to compare cross-national prevalence of psychotropic medication use in youth. METHODS: A population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0-4, 5-9, 10-14, and 15-19), gender, drug subclass pattern and concomitant use. The data include insured youth aged 0-19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157). RESULTS: The annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5-2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth. CONCLUSION: Prominent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.

Antidepressant prevalence for youths: a multi-national comparison.

OBJECTIVE: To compare antidepressant prevalence data in youths across three western European countries (Denmark, Germany, and the Netherlands) with US regional data in terms of age and gender and to show proportional subclass antidepressant (ATD) use. METHOD: A population-based analysis of administrative claims data for the year 2000 was undertaken in 0 to 19-year-old enrollees who were part of the insured populations from four countries having a total of from 72,570 to 480,680 members. RESULTS: ATD medication utilization in the US dataset (1.63%) exceeded that of three Western European countries (prevalence ranged from 0.11 to 0.54%) by at least 3-fold. There were major variations in the use of subclasses: tricyclic antidepressants (TCAs) predominated in Germany while selective serotonin reuptake inhibitors (SSRIs) predominated in the US, Denmark and the Netherlands. CONCLUSIONS: Cross-national variations should be further explored to understand the factors related to these differences and how prevalence differences relate to effectiveness and safety. Community-based cohorts should be followed to establish outcomes in the usual practice setting.

Antidepressant use in children and adolescents in Germany.

OBJECTIVE: The expanded use of antidepressants in youth has been the subject of numerous studies and some concerns in recent years. This study describes prescription patterns of antidepressants (ATD) for youths in Germany for the years 2000-2003 and includes prescription use of St. John's Wort. METHODS: Prescription data from a health insurance organization with 1.4 million members per year across Germany, of whom approximately 280,000 were under 20 years of age, were accessed. Total age- and gender-specific ATD yearly utilization rates were computed. Prevalence was defined as the dispensing of 1 or more prescriptions for an ATD per calendar year per 1000 continuously enrolled youth. RESULTS: ATD prevalence was 3.43 per 1000 (95% Confidence Interval [CI], 3.21-3.65) in 2000 and 3.74 per 1000 (3.25-3.97) in 2003. St John's Wort products, which are approved for antidepressant use by the German drug agency, and tricyclic antidepressants (TCAs), accounted for more than 80% of antidepressant use. Although selective serotonin reuptake inhibitors (SSRIs) represented only 15% of antidepressant use, there was a doubling of its use over the 4-year period. Adolescent girls (age, 15-19 years) had utilization rates ranging from 11.44 to 13.82 per 1000, and accounted for most ATD use. Overall, females were twice as likely as males to get an antidepressant. Among users, there were low rates of multiple medication use (5.6% used more than one class of ATD, and 6.7% more than one drug). CONCLUSIONS: Prescription patterns in Germany reveal predominate use of St. John's Wort and TCAs, which contrasts sharply with U.S. patterns, wherein SSRIs predominate. Also, in the United States, unlike Germany, 5-9- and 10-14 year olds receive sizable proportions of ATDs. Labeling status (only herbal hypericum preparations and TCAs are labeled for the treatment of depression in children and adolescents in Germany) and cost restrictions appear to influence the prescribing pattern of doctors in Germany. Recent treatment recommendations of national and international regulatory agencies need to take into account the different national situations.