Personalised Psychiatry Depression. Amsterdamse school Aartjan TF Beekman Dpt Psychiatry VUmc & GGZinGeest Amsterdam

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1 Personalised Psychiatry Depression Amsterdamse school Aartjan TF Beekman Dpt Psychiatry VUmc & GGZinGeest Amsterdam

2 Disclosure Informatie Beekman Onderzoek: Eli Lilly, Astra Zeneca, Jansen, Shire Adviesraad: Continuum Psychiatrie Presentaties: Lundbeck, Eli Lilly

3 Where is health care going? Preventive Medicine Personalised Medicine Precision Medicine

4 Personalised Medicine

5 Personalised Psychiatry Treatments targeted towards select groups within and across diagnostic categories Based on mechanism of action and effectiveness Revolutionises diagnosis and treatment Revolutionises trial methodology

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8 Promise Improve precision allocation treatment Reduce damage due to side effects Guide diagnosis towards etiology, development disorder and treatment effect Guide interaction patient towards shared decision making Scientific model that is more likely to help discovering mechanisms for etiology and treatment response

9 Q: Do we have a case for Personalised Psychiatry? Focus on depression Is personalised approach necessary and helpful? Are sufficient data in place? Which steps should we take first

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11 Depression: costs to EU economy 19% 8% Outpatient Care Pharmaceuticals Hospitalisation Lost Employment 64% 9% 41 billion direct costs 77 billion productivity losses Sobocki et al, J Mental Health Policy & Econ, 2006 Leal et al, European Heart Journal, billion productivity losses for cardiovascular disease

12 Disability Benefits GB % 22% 3.9 billion per annum 18% 40% 8% 6% Other Nervous System Musculoskeletal System Mental and Behavioural Disorders Circulatory and Respiratory System Injury, Poisoning, External Causes Source: Department of Work and Pensions, 2007

13 Major Cause of Early Retirement

14 Impacts on costs chronic disease Welch et al 2009

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17 Diagnosis does not predict outcome (Spijker et al, Br J Psychiatry 2002: ) 1,2 1,0 50% recovered < 3 mnths 20% duration > 1 year,8,6,4 proportion still in episode,2 0,0 censored duration (months) Fig. 1 Survival curve of a cohort (n=250) with newly originated (first or recurrent) major depressive episodes in the general population

18 J Clinical Psychiatry 2010,

19 NNT antidepressiva chronische depressie NNT = 6 voor response NNT = 7 voor remissie

20 NNT psychotherapie chronische depressie = 7,7 Effect size d = 0,23

21 Comment proportion still in episode 1,2 1,0,8,6,4, ,0 censored High recovery High placebo response Treatment unnecessary Low effect size High NNT 2. Low recovery Low placebo response Monotherapy uneffective Low effect size High NNT duration (months)

22 Natuurlijk beloop depressie Healthy universal prevention Risk group selective prevention Prodromal indicated prevention 2nd episode Full remission: relapse prevention Residual symptoms: relapse prevention FIRST episode Chronicity

23 Clinical Staging in Psychiatry: Patrick McGorry; Am J Psychiatry 2007; 164: 859

24 Staging Lung Cancer

25 Stelling We behandelen onze patienten te laat En laten daardoor window of opportunity voorbijgaan

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27 Staging depression: Hetrick 2008 Stage 0 Elevated risk but no symptoms 1a Mild subthreshold symptoms (aspecific) 1b More severe subthreshold symptoms (GAF <70) 2 First episode full blown MDD 3a Incomplete Remission 3b Relapse with incomplete recovery 3c Multiple relapses with incomplete recovery 4 Severe persistent depression

28 Effecten behandeling per stage Stage Interventie Stelsel Effect 0 Selectieve Preventie Basis GGZ/zelf Prima NNT + 10 OGGZ 1a 1b Geindiceerde Preventie Basis GGZ/zelf Prima NNT Collaborative Care Basis GGZ Prima NNT 2-3 3a Behandelprogramma 3b Relapse preventie 3c 4 ECT CBASP Specialist Basis GGZ/zelf Hoog specialistisch Wie weet dit? Prima: NNT 5 Sterk effect Sterk effect

29 Clinical staging of Major Depressive Disorder: an empirical exploration. Judith Verduijn et al. NESDA data 2393 participants

30 Tussenstand: staging Is eenvoudig Iedereen snapt dit Kunnen we morgen gaan doen Helpt erg om heterogeniteit depressie te verminderen Integreer preventie en behandeling Krachtige voorspeller beloop Krachtige voorspeller effect behandeling Helpt bij indicatiestelling

31 Personalised depression care? 2. Clinical Profiling

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36 Comment Depression is probably a progressive disorder in some patients Finding out in which patients, is what personalised medicine is all about Strong case for staging and prevention through early intervention Agenda for future research

37 Farmacogenetics as a candidate profiler for personalised care

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39 Psychiatric disorders are not restricted to the brain

40 J Clin Psychiatry 2011 Arch Gen Psychiatry 2011, 65, Arch Gen Psychiatry 1997

41 Pretreatment brain glucose metabolism (PET) RCT: CBT versus citalopram 12 weeks Outcome: remission vs non-response TSB: predicts both response to one treatment and non-response to the other

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44 Comment CBT and citalopram equally effective No main effect in any region PET Right anterior insula strongest effect Insula hypometabolism remission CBT Insula hypermetabolism remission cital Multiple regions: circuitary or combined effect Small study!

45 Conclusions Personalised Psychiatry is both necessary and desirable Improve effectiveness and efficiency of care Prevent exposure to treatments that do not work Framework that is favourable for shared decision making

46 Conclusions Revolutionises diagnosis, treatment and research In depression: data in place tot get started Clinical Staging and profiling helpful framework and something to get started with

47 Diagnose: Depressie, Matig ernstige episode die nu 8 maanden bestaat. Stagering 3c: Derde episode, met in perioden tussen episoden onvolledig herstel. Eerste episode op 18e jaar. Profiel angst pijn alc bipo neurotic impuls metab hpa inflam chronob seizon trauma event family suic