Publications (10)71.48 Total impact
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Article: Editorial.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 11/2012; 22(11):769. · 3.68 Impact Factor -
Article: European licensing of maintenance treatment in schizophrenia.
The Lancet 08/2012; 380(9841):562-3. · 38.28 Impact Factor -
Article: The placebo arm in clinical studies for treatment of Psychiatric Disorders: A Regulatory Dilemma.
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ABSTRACT: The use of placebo in clinical trials, and, related to this, ethical and feasibility aspects, are often debated. However, regulatory authorities must ensure that only new drugs with a positive benefit/risk would be granted a marketing authorization. It is therefore not surprising that they often put forward the need for placebo control in clinical trials in an area where many trials fail, and assay sensitivity is not self-evident. To illustrate the complexity that regulatory authorities encounter when faced with the registration dossier of products in the main psychiatric therapeutic areas, Major Depressive Disorder (MDD) and schizophrenia, the trial outcome for products receiving an opinion in the EU during the past 15 years were reviewed. European Public Assessment Reports and registration files. A total of 45 studies qualified for analysis. For the indication MDD 38% of the studies (10/26) were recorded as failed, and another 15% (4/26) as negative. For schizophrenia, these figures were 16% (3/19) and 11% (2/19). Further exploration of the trials in MDD revealed an inconsistent pattern in terms of magnitude of placebo- and drug-mediated response (i.e. similar studies with consistent placebo response provided different treatment outcomes). From a regulatory perspective the dilemma of a priori exclusion of the placebo arm in clinical trials in the domains of depression or schizophrenia cannot be solved at this time as long as factors influencing trial variability are not better identified or understood. This counts in particular for MDD where the added drug effect is not consistent across trials with almost identical inclusion criteria. Unfortunately, this trend has not changed over the past 15 years. However, all efforts should be taken to optimize the clinical development of drugs in the psychiatric domain, and improve the intrinsic quality of the clinical trials in order to allow for a different viewpoint.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2012; 22(11):804-11. · 3.68 Impact Factor -
Article: Implementation of the harmonized EU isotretinoin Pregnancy Prevention Programme: a questionnaire survey among European regulatory agencies.
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ABSTRACT: There is little information on the status of the implementation of the isotretinoin Pregnancy Prevention Programme (PPP) in the EU, and on compliance with this programme by the regulatory agencies. The aim of the study was to obtain information on implementation of the harmonized PPP of isotretinoin in the EU member states plus Norway and Iceland. In January 2009, a questionnaire (request for non-urgent information [NUI]) was sent to all 25 EU member states, plus Norway and Iceland, to collect information on the implementation status of the PPP and its effectiveness. The response rate was 82% (22 of the 27 countries). In 21 of the 27 member states, isotretinoin is marketed and the PPP is in force, and in 18 of the 22 responding countries, the total required elements (seven) following a formal EU review are incorporated in the PPP. Seven member states had additional measures in place. In spite of implementation of the PPP and additional measures, a total of 143 isotretinoin-exposed pregnancies have been reported in 16 of the 22 responding member states since implementation of the harmonized PPP. Despite implementation of the isotretinoin PPP in most member states, isotretinoin-exposed pregnancies were reported. This has led some member states to implement additional measures to the PPP, resulting in inconsistency with the approach agreed in 2003 following the European-wide review. It has been further suggested that common elements should be developed for PPPs for all medicines that are known to carry a high teratogenic risk.Drug Safety 11/2011; 35(1):27-32. · 3.63 Impact Factor -
Article: The EU paediatric regulation: effects on paediatric psychopharmacology in Europe.
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ABSTRACT: 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.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2011; 21(8):565-70. · 3.68 Impact Factor -
Article: Insomnia medication: do published studies reflect the complete picture of efficacy and safety?
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ABSTRACT: Selective publication can have a deleterious effect on evidence based medicine, health policy decision making and treatment guidelines. Using the European Public Assessment Reports (EPARs) as reference, this study examined selective publication and selective reporting of efficacy and safety of insomnia medication. EPARs of with three insomnia medications were used to identify all clinical trials that were performed between 1998 and 2007 for the purpose of registration in the EU. The matching publication for each trial was searched through a systematic literature search. Accuracy of information in the publications was examined by comparison to the information in the EPARs. Only 55% of the trials with insomnia medications identified in EPARs were published. Positive trials were approximately two times more likely to be published. The lag time from study completion to publication was shorter for the positive compared to the negative trials. Sample size did not correlate with publication of negative trials. The meta-analysis of the effect size of insomnia medication was 1.6 times larger in the published data compared to the complete data. While the primary end points of the trials were reported reliably in the publications, remarkable inconsistencies were detected in the reporting of the secondary end points, methods, results and, especially safety. In conclusion, selective publication and reporting lead to an overestimation of efficacy and underestimation of safety of insomnia products. Authors of treatment guidelines should be aware of this bias. EPARs/FDA reviews provide a more unbiased view of the benefit-risk balance of insomnia and other medications and hence these documents should be consulted by e.g. authors of meta-analyses and of treatment guidelines.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 11/2010; 21(7):500-7. · 3.68 Impact Factor -
Article: Empathy dysfunction in children and adolescents with disruptive behavior disorders.
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ABSTRACT: In this essay, we focus on empathy in children and adolescents with disruptive behavior disorders (DBD), based on the assumption that lack of empathy is a risk factor for the development of DBD. We reflect on the heterogeneity of DBD, the complex nature of the empathy construct, discuss empathy's role in aggression, and review recent findings from studies on empathic skills in children and adolescents with DBD. Research suggests that the mechanisms underlying empathy problems may be different for DBD subtypes. Individuals with psychopathic tendencies may show a selective impairment in empathy with sadness and fear due to abnormalities in neural circuits connected with the amygdala. Individuals without these tendencies may show little empathy for a variety of reasons, such as hostile attributions, anxiety and/or poor regulatory skills. Understanding more about the nature and causes of empathy dysfunction in DBD could aid in identifying subtypes and help to improve prevention and intervention programs. Suggestions for future research are made.European journal of pharmacology 10/2009; 626(1):97-103. · 2.59 Impact Factor -
Article: Requirements for generic anti-epileptic medicines: a regulatory perspective.
Journal of Neurology 08/2009; 256(12):1966-71. · 3.47 Impact Factor -
Article: Psychopharmacology for children: from off label use to registration.
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ABSTRACT: Pharmacological treatment of children and adolescents is largely based on evidence from adults' studies. There is, however, growing awareness that this evidence cannot simply be extrapolated to children. The Dutch Medicines Evaluation Board (MEB) in collaboration with the Child and Adolescent section of the Dutch Association of Psychiatry and the National Expertise Centre Child and Adolescent Psychiatry have organised a workshop to discuss the kind of evidence that would be necessary and the methods involved. There was consensus about the need to demonstrate efficacy in targeted disorders as well as symptoms within specific disorders and about the need for separate evidence for children and for adolescents. In addition, too little is known about safety, especially long-term safety, as consequences of treatment. Main issues are effects on growth, cognitive, motor, emotional, and sexual development, metabolic symptoms, cardiotoxicity, and dependence. Specific methodological issues were discussed, such as the role of different informants and the high rate of comorbidity.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2009; 19(8):603-8. · 3.68 Impact Factor -
Article: HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study.
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ABSTRACT: In a previous study, we found an association between 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) polymorphisms and the occurrence of the metabolic syndrome in patients using antipsychotics. In the current study, we set out to replicate our findings in another sample of patients and to explore in a pooled analysis of both samples the influence of the effect of individual antipsychotics. Data for this cross-sectional study came from 2 different samples, the original sample (n = 112) and the replication sample (n = 164). Primary end point was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the promoter region of the HTR2C gene [HTR2C:c.1-142948(GT)n, rs3813929 (-759 C/T), and rs518147 (-697 G/C)] and an intragenic polymorphism (rs1414334:C>G). The variants of HTR2C:c.1-142948(GT)n (odds ratio [OR], 1.69; 95% confidence interval [CI], 0.75-3.81) and rs1414334 (OR, 2.35; 95% CI, 0.96-5.77) were not significantly associated with the metabolic syndrome in the replication sample but did show significance in the pooled analysis (OR, 2.09; 95% CI, 1.12-3.91; and OR, 2.35; 95% CI, 1.19-4.62, respectively). The variant rs1414334 C allele was specifically associated with the metabolic syndrome in patients using clozapine (OR, 9.20; 95% CI, 1.95-43.45) or risperidone (OR, 5.35; 95% CI, 1.26-22.83). This study extends previous findings to a larger sample of patients and implicates specific antipsychotic drugs. The increased risk for the metabolic syndrome is particularly strong in carriers of the rs1414334 C allele using clozapine or risperidone.Journal of clinical psychopharmacology 02/2009; 29(1):16-20. · 5.09 Impact Factor
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Institutions
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2009–2012
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College ter Beoordeling van Geneesmiddelen
Utrecht, Provincie Utrecht, Netherlands
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