1. Psychofarmaca in de dagelijkse praktijk – evidence based medicine? Rob Heerdink

2. Rob Heerdink Pharmacoepidemiology & Pharmacotherapy Utrecht Institute for Pharmaceutical Sciences Universiteit Utrecht The Netherlands www.pharm.uu.nl/epithera

9. evidence based medicine ?

10. Drug development discovery Discovery & screening Proof of Concept first administration to man registration & launch approx. 10-12 years 10,000 Pre-clinical development 15-30 Fase I/IIa 10-15 Fase IIb/III 1 5 preclinical clinical (I-III) phase IV

14. Science 2005; 307: 196-8.

15. A numbers game Clinical trials Market

17. Too short

18. Herald Tribune 30-09-96

19. “ It was easy money during the first trial, but that spinal tap really hurt.” Herald Tribune 30-09-96

26. Are Subjects in Pharmacological Treatment Trials of Depression Representative of Patients in Routine Clinical Practice? Mark Zimmerman, M.D., Jill I. Mattia, Ph.D., and Michael A. Posternak, M.D Am J Psychiatry 159:469-473, March 2002 ‘ Of 346 patients with ‘major depression’ only 14% are eligible according to inclusion criteria for trials with antidepressants’

27. Tussen 1969 en 2008 zijn er 101 trials gedaan naar het effect van antipsychotica op gedragsproblemen Totaal 12,926 deelnemers 1165 (9%) verstandelijke beperking 873 (7%) kinderen/jeugd Cave: kleine trials (n=57) onduidelijke diagnose onduidelijke maat VB onduidelijke uitkomstmaat korte followup A Scheifes et al 2009

28. comparator Heres et al. Am J Psych, Feb 2006 sponsored drug olanzapine risperidon clozapine ziprasidone ami sulpiride Olanzapine (Lilly) 5 / 0 2 / 1 2 / 0 1 / 0

29. comparator Heres et al. Am J Psych, Feb 2006 sponsored drug olanzapine risperidon clozapine ziprasidone ami sulpiride Olanzapine (Lilly) 5 / 0 2 / 1 2 / 0 1 / 0 Risperidon (Janssen) 3 / 1 1 / 0

30. comparator Heres et al. Am J Psych, Feb 2006 sponsored drug olanzapine risperidon clozapine ziprasidone ami sulpiride Olanzapine (Lilly) 5 / 0 2 / 1 2 / 0 1 / 0 Risperidon (Janssen) 3 / 1 1 / 0 Clozapine (Novartis) 1 / 0 1 / 0

31. comparator Heres et al. Am J Psych, Feb 2006 sponsored drug olanzapine risperidon clozapine ziprasidone ami sulpiride Olanzapine (Lilly) 5 / 0 2 / 1 2 / 0 1 / 0 Risperidon (Janssen) 3 / 1 1 / 0 Clozapine (Novartis) 1 / 0 1 / 0 Ziprasidone (Pfizer) 1 / 1 Amisulpiride (Sanofi) 1 / 0

33. evidence based medicine ?

34. medicine based evidence Heerdink et al Br J Psychiatry 2004

35. Geregistreerde indicaties bij kinderen Benzodiazepinen - Antidepressiva - Antipsychotica - Stimulantia 6+

36. www.kenniscentrum-kjp.nl

39. Antipsychotica

40. Antipsychotica Kalverdijk et al Psych Serv 2008

42. Antidepressiva

48. Welk middel? Middel Effectief Atypische antipsychotica Clozapine: therapieresistente schizofrenie Risperidone: vermindering “vijandigheid” Olanzapine: BPD Antidepressiva Schizofrenie, autisme, cluster B phs Anticonvulsiva Valproaat: cluster B phs Bètablokkers Schizofrenie

49. Presque tous les hommes meurent de leurs remèdes, et non pas de leurs maladies. Moliere, Le Malade Imaginaire (1673), Act III, sc. iii

50. Risk assessment

52. Medicatie zonder goede start en zonder zicht op een duidelijk einde is slechte therapie email: e.r.heerdink@uu.nl twitter: @robheerdink www.slideshare.net/robheerdink