Luuk J. Kalverdijk

Use of Antipsychotic Drugs Among Dutch Youths Between 1997 and 2005

OBJECTIVE The authors examined prevalence, incidence, and duration of antipsychotic drug use in the northern and eastern regions of the Netherlands between 1997 and 2005 among youths in regard to age, gender, and class of drug. METHODS Prescription drug dispensing data were collected from community pharmacies in the northern Netherlands (www.iadb.nl). Prevalence, incidence, and duration of use were studied among roughly 100,000 youths ranging in age from infancy to age 19 years, calculated by age group (zero to four years, five to nine years, ten to 14 years, and 15 to 19 years), for boys and girls, and for first- and second-generation antipsychotics. Duration of use was compared between youths who started antipsychotic treatment in 1998-1999 and those who started in 2001-2002. RESULTS From 1997 to 2005, prevalence increased from 3.0 to 6.8 per thousand. Prevalence was highest among ten-year-olds to 14-year-olds (11 per thousand), especially among boys (17 per thousand). The increased prevalence was mainly attributable to an increased use of second-generation antipsychotics and to a longer duration of use. Median duration of use doubled from .8 year in 1998-1999 to 1.6 years in 2001-2002. CONCLUSIONS Second-generation antipsychotic drugs were increasingly prescribed, and for longer periods of time, to younger children, probably because of new indications. This practice increases the exposure of a young population to (partly unknown) risks.

Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012

Following the FDA black box warning in 2004, substantial reductions in antidepressant (ATD) use were observed within 2 years in children and adolescents in several countries. However, whether these reductions were sustained is not known. The objective of this study was to assess more recent trends in ATD use in youth (0-19 years) for the calendar years 2005/6-2012 using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). In a repeated cross-sectional design, the annual prevalence of ATD use was calculated and stratified by age, sex, and according to subclass and specific drug. Across the years, the prevalence of ATD use increased from 1.3% to 1.6% in the US data (+26.1%); 0.7% to 1.1% in the UK data (+54.4%); 0.6% to 1.0% in Denmark data (+60.5%); 0.5% to 0.6% in the Netherlands data (+17.6%); and 0.3% to 0.5% in Germany data (+49.2%). The relative growth was greatest for 15-19 year olds in Denmark, Germany and UK cohorts, and for 10-14 year olds in Netherlands and US cohorts. While SSRIs were the most commonly used ATDs, particularly in Denmark (81.8% of all ATDs), Germany and the UK still displayed notable proportions of tricyclic antidepressant use (23.0% and 19.5%, respectively). Despite the sudden decline in ATD use in the wake of government warnings, this trend did not persist, and by contrast, in recent years, ATD use in children and adolescents has increased substantially in youth cohorts from five Western countries.

Large increase of the use of psycho-stimulants among youth in the Netherlands between 1996 and 2006.

AIM To describe the use of psycho-stimulants in the Netherlands between 1996 and 2006 in children and adolescents, and in relation to age and sex. METHODS With the pharmacy prescription database the IADB.nl, yearly prevalences of psycho-stimulants per 1000 children were calculated, as was the length of psycho-stimulant use with Kaplan-Meier method in SPSS 12.0. RESULTS Psycho-stimulant use increased in boys (0-19) from 4.5 per thousand in 1996 to 31.1 per thousand in 2006 and for girls from 0.7 to 8.1 per thousand, respectively. The largest increase was among boys aged 10-19 years. There is a trend towards prescribing the sustained release preparation of methylphenidate (Concerta). CONCLUSIONS In the Netherlands a large increase in psycho-stimulants use is observed. However, in the Netherlands the prevalence ratio male/female declined from 6.4 in 1996 to 3.8 in 2006.

Long-Acting Methylphenidate-OROS in Youths with Attention-Deficit Hyperactivity Disorder Suboptimally Controlled with Immediate-Release Methylphenidate. A study of cost effectiveness in The Netherlands.

AbstractBackground: Attention-deficit hyperactivity disorder (ADHD) is the most common mental health disorder in youths. Stimulants are the drugs of first choice in the treatment of ADHD. It has been suggested that full costs associated with the treatment of ADHD may be reduced by once-daily administration regimens of stimulants. Objectives: To estimate the cost effectiveness of treatment with long-acting methylphenidate osmotic release oral system (OROS) [Concerta®] for youths with ADHD for whom treatment with immediate-release (IR) methylphenidate is suboptimal. Study design: We developed a Markov model to obtain an incremental cost-effectiveness ratio (ICER). The analysis covered 10 years, with a Markov cycle of 1 day. Costs (in 2005 euros [€]) included medication, consultations and treatment interventions, and additional costs for attending special education. Quality-adjusted life-years (QALYs) were used as the effectiveness measure. Outcome probabilities were taken from the medical literature and an expert panel of five child psychiatrists and paediatricians. Univariate sensitivity analyses were performed to assess the robustness of the base-case estimate. Multivariate sensitivity analysis was used to estimate a worst- and best-case ICER. Results: The ICER of methylphenidate-OROS treatment in youths with ADHD for whom treatment with IR methylphenidate is suboptimal was €2004 per QALY. Total costs after 10 years were €15 739 for the IR methylphenidate pathway and €16 015 for the methylphenidate-OROS pathway. In the univariate sensitivity analysis, the ICER was sensitive to changes in resource use and the robability of stopping stimulant treatment in favour of IR methylphenidate. An ICER of 0 was reached with a 6.2% price reduction of methylphenidate-OROS. Conclusion: Methylphenidate-OROS is a cost-effective treatment for youths with ADHD for whom treatment with IR methylphenidate is suboptimal. Higher medication costs of methylphenidate-OROS were compensated for by savings on resource use, yielding similar 10-year costs compared with treatment with IR methylphenidate. Our analysis is sensitive to both clinical parameters and (differences in) resource utilization and costs between the groups modelled, warranting further research within clinical trials and observational databases, and into the full scope of costs.

International trends in clozapine use: a study in 17 countries

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.

The EU paediatric regulation: effects on paediatric psychopharmacology in Europe.

Child and adolescent psychiatry is a relatively young field and the recognition, classification, and treatment of disorders in children and adolescents lag behind those in adults. In recent years there is an increasing awareness of the differences between children and adults in psychopathology and pharmacology. Related to this new paediatric regulations have been introduced. This article reviews the regulatory and legislative measures that were adopted in the EU in 2007 and the subsequent impact of these measures on the field of paediatric psychopharmacology. The consequences of the paediatric regulation in the EU are reflected in several domains: regulatory, research aimed at drug development and clinical practices. In the regulatory domain, the consequences include: new paediatric indications, inclusion of special (class) warnings, specification of dose regimens, and information on safety specific to children and adolescents, and development of new medicinal formulations. The paediatric regulation leads to timely development of paediatric friendly formulations and better quality of the clinical evidence. In clinical practices, an increased awareness of the uniqueness of paediatric pharmacology is emerging among medical professionals, and subsequent improvement of medical care (i.e. correct doses, appropriate formulation, monitoring for expected adverse events). In addition, clinical guidelines will have to be revised more frequently in order to integrate the recently acquired knowledge. The new regulations stimulate transparency and discussions between academia, pharmaceutical industry, and regulators. The purpose is to optimize clinical research and obtain evidence for paediatric psychopharmacology, thereby providing adequate support for treatment.

International trends in antipsychotic use : A study in 16 countries, 2005-2014

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.

Trends in ADHD medication use in children and adolescents in five western countries, 2005-2012

Over the last two decades, the use of ADHD medication in US youth has markedly increased. However, less is known about ADHD medication use among European children and adolescents. A repeated cross-sectional design was applied to national or regional data extracts from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The prevalence of ADHD medication use was assessed, stratified by age and sex. Furthermore, the most commonly prescribed ADHD medications were assessed. ADHD medication use prevalence increased from 1.8% to 3.9% in the Netherlands cohort (relative increase: +111.9%), from 3.3% to 3.7% in the US cohort (+10.7%), from 1.3% to 2.2% in the German cohort (+62.4%), from 0.4% to 1.5% in the Danish cohort (+302.7%), and from 0.3% to 0.5% in the UK cohort (+56.6%). ADHD medication use was highest in 10-14-year olds, peaking in the Netherlands (7.1%) and the US (8.8%). Methylphenidate use predominated in Europe, whereas in the US amphetamines were nearly as common as methylphenidate. Although there was a substantially greater use of ADHD medications in the US cohort, there was a relatively greater increase in ADHD medication use in youth in the four European countries. ADHD medication use patterns in the US differed markedly from those in western European countries.

Antipsychotics in Dutch youth: Prevalence, dosages, and duration of use from 2005 to 2015

OBJECTIVES The use of antipsychotic drugs by youth is associated with serious side effects, especially when prescribed in higher dosages and for a longer period. Despite this, little is known about recent trends in the dosages and duration of use of antipsychotic drugs in children and adolescents. The aim of this study was to describe trends in prevalence, incidence, dosages, duration of use, and preceding psychotropic medication in Dutch youth who had been prescribed antipsychotic drugs from 2005 to 2015. METHODS We analyzed 84,828 antipsychotic prescriptions of youths aged 0-19 years between 2005 and 2015, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). RESULTS Since a peak of 9.8 users per 1000 youths in 2009, prevalence rates stabilized. Dosages in milligram per kilogram declined for the most frequently prescribed antipsychotic drugs during the study period. The median duration of use was 6.0 (95% CI 5.4-6.6) months. Boys used antipsychotic drugs significantly longer than girls, with a median of 6.9 (95% CI 6.1-7.7) versus 4.6 (95% CI 3.9-5.3) months (p < 0.01). Of the youths prescribed antipsychotics, 12.4% used them for at least 48 months. The majority of youths had used other psychotropic agents in the year before the start of an antipsychotic drug (62.4% in 2005 and 64.7% in 2015). CONCLUSIONS Despite a stabilization of usage rates and decline in dosages and duration of use, one in eight youths still used antipsychotic drugs for 4 years or longer. A substantial share of youths may, therefore, be at high risk for serious side effects.

InforMatrix for attention deficit hyperactivity disorder

The purpose of this review is to facilitate discussion on drug selection for the treatment of ADHD by using only clinically relevant selection criteria and providing an up-to-date overview. The InforMatrix method was used to select drugs to treat attention deficit hyperactivity disorder (ADHD). The following selection criteria were applied: clinical efficacy, safety, tolerability, ease of use, applicability, and cost. The drugs approved for ADHD in the Netherlands were included in the analysis, namely: atomoxetine, immediate-release methylphenidate, and various formulations of slow-release methylphenidate (Concerta, Equasym and Medikinet). Most studies are of limited quality, duration, and size. In one study, Concerta was more effective than atomoxetine. Although no relevant differences were seen in other comparative studies, the clinical experience with atomoxetine is still limited and unexpected toxicity cannot be excluded; few studies have been published with Equasym and Medikinet. No major differences were seen in general tolerability between the drugs. The ease of use of immediate-release methylphenidate is less than for the other drugs. The acquisition cost of immediate-release methylphenidate is considerably lower than that of the slow-release formulations. Atomoxetine is the most expensive drug. The InforMatrix program is available in an interactive format. It enables the user to judge both the importance of the selection criteria and the properties of each therapeutic option per criterion on the basis of his or her own personal expertise and/or the present document.