International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia.

Introduction: Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. Methods: We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Results: Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. Discussion: In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.

[Sex-specific differences in drug utilisation in different phases of life]. / Geschlechtsspezifische Inanspruchnahme bei der Arzneimittelversorgung in verschiedenen Lebensphasen.

The aim of the present study is to analyse sex-specific differences in drug utilisation during different phases of life using relevant diseases as examples. We used a cohort of 1.7 million subjects who were insured with the Gmünder ErsatzKasse (GEK), a German health insurance fund, for at least one day in all four quarters of 2009. We analysed subjects with outpatient diagnoses of the following diseases: attention-deficit/hyperactivity disorder (ADHD) (0-17 years), hypothyroidism (18-49 years), osteoporosis (50-79 years) and coronary heart disease (80 + years). Analysis was performed on an active-substance level. A number of differences were observed in drug treatment for the selected diseases (for example, substances for ADHD were prescribed more often in males and for hypothyroidism more often in females), as well as in prescribing practices relating to other drugs used in these groups. However, clear explanations for these differences, such as drug approval status, were not always apparent.

[Differences in sociodemographic characteristics, health, and health service use of children and adolescents according to their health insurance funds]. / Unterschiede in den soziodemografischen Merkmalen, der Gesundheit und Inanspruchnahme bei Kindern und Jugendlichen nach ihrer Krankenkassenzugehörigkeit.

Differences in the socioeconomic characteristics and morbidity between members of German private and statutory health insurance funds and also between several statutory health insurances have been shown for adults. We used data from the National Health Survey for Children and Adolescents (KiGGS) to study differences in sociodemographic characteristics, health risks, morbidity, and health service use in child and adolescent insurants of different types of health insurance funds (Ersatzkasse, Allgemeine Ortskrankenkasse, Betriebskrankenkasse , Innungskrankenkasse, other statutory health insurance funds, private health insurance). Differences in the proportion of respondents with a migration background, somatic diseases, psychopathological problems, and contact with a dentist between the different health insurance fund types were found. These results should be considered in studies on health inequalities, which often focus solely on differences between statutory and private health insurance. Our results are also of relevance for health services research using the claims data of health insurance funds.

Aripiprazole as an adjunct to clozapine therapy in adolescents with early-onset schizophrenia: a retrospective chart review.

INTRODUCTION: Combination of antipsychotic substances is a therapeutic option increasingly applied in patients with schizophrenia, who do not respond to antipsychotic monotherapy. Recently, various reports on combination of clozapine with aripiprazole in adults have been published. As there is not yet data on adolescent patients, we aimed to study the above-mentioned augmentation strategy in this population. METHODS: We included 15 patients with schizophrenia from a child and adolescent psychiatric department (8 male; mean age 19.3 [SD+/-1.2, range 17.2-21.2] years). Patients had been under clozapine treatment, followed by aripiprazole augmentation. Retrospectively, patients' medical records were reviewed, using a rating scale in analogy to the Clinical Global Impressions (CGI) scale. RESULTS: Mean observation time was 11.1 [SD+/-9.7] months. Mean CGI-Severity scores improved significantly (p=0.003, d=0.76) from 5.3 (baseline) to 4.5 (endpoint; last observation carried forward (LOCF)). CGI-Improvement scores decreased from 3.7 (after 1 month) to 3.3 (endpoint; LOCF) (p=0.212, d=0.45). CONCLUSIONS: In adolescents with schizophrenia, aripiprazole augmentation of clozapine treatment might be an effective therapeutic strategy. Prospective studies for this age group are required to obtain more specific clinical data on clinical effectiveness.