Personalised Psychiatry Depression Amsterdamse school 31012014 Aartjan TF Beekman Dpt Psychiatry VUmc & GGZinGeest Amsterdam Disclosure Informatie Beekman • Onderzoek: Eli Lilly, Astra Zeneca, Jansen, Shire • Adviesraad: Continuum Psychiatrie • Presentaties: Lundbeck, Eli Lilly Where is health care going ? • Preventive Medicine • Personalised Medicine • Precision Medicine Personalised Medicine 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 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 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 Depression: costs to EU economy Outpatient Care Pharmaceuticals Hospitalisation 19% Lost Employment 8% 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, 2006 €35 billion productivity losses for cardiovascular disease Disability Benefits GB 2007 22% 6% € 3.9 billion per annum 18% 40% 8% 6% Other Mental and Behavioural Disorders Nervous System Circulatory and Respiratory System Musculoskeletal System Injury, Poisoning, External Causes Source: Department of Work and Pensions, 2007 Major Cause of Early Retirement Impacts on costs chronic disease Welch et al 2009 Diagnosis does not predict outcome (Spijker et al, Br J Psychiatry 2002: 202-213) • 50% recovered < 3 mnths 1,2 • 20% duration > 1 year 1,0 ,8 ,6 proportion still in episode ,4 ,2 0,0 0 censored 10 20 30 duration (months) Fig. 1 Survival curve of a cohort (n=250) with newly originated (first or recurrent) major depressive episodes in the general population J Clinical Psychiatry 2010, 1300-1306 • NNT antidepressiva chronische depressie • NNT = 6 voor response • NNT = 7 voor remissie • NNT psychotherapie chronische depressie = 7,7 • Effect size d = 0,23 Comment 1,2 1. High recovery High placebo response Treatment unnecessary Low effect size High NNT 1,0 ,8 1 ,6 2. Low recovery Low placebo response Monotherapy uneffective Low effect size High NNT proportion still in episode ,4 ,2 2 0,0 0 duration (months) censored 10 20 30 Natuurlijk beloop depressie Healthy universal prevention Risk group selective prevention Prodromal indicated prevention Full remission: relapse prevention …… 2nd episode Residual symptoms: relapse prevention …… Chronicity FIRST episode Clinical Staging in Psychiatry: Patrick McGorry; Am J Psychiatry 2007; 164: 859 Staging Lung Cancer Stelling • We behandelen onze patienten te laat • En laten daardoor ‘window of opportunity’ voorbijgaan Staging depression: Hetrick 2008 Stage 0 Elevated risk but no symptoms 1a 1b 2 Mild subthreshold symptoms (aspecific) More severe subthreshold symptoms (GAF <70) First episode full blown MDD 3a 3b 3c 4 Incomplete Remission Relapse with incomplete recovery Multiple relapses with incomplete recovery Severe persistent depression Effecten behandeling per stage Stage Interventie Stelsel Effect 0 Selectieve Preventie Basis GGZ/zelf OGGZ Prima NNT + 10 1a 1b Geindiceerde Preventie Basis GGZ/zelf Prima NNT + 8 2 Collaborative Care Basis GGZ Prima NNT 2-3 3a 3b 3c Behandelprogramma Relapse preventie Specialist Basis GGZ/zelf Wie weet dit? Prima: NNT 5 4 ECT CBASP Hoog specialistisch Sterk effect Sterk effect Clinical staging of Major Depressive Disorder: an empirical exploration. Judith Verduijn et al. • NESDA data – 2393 participants 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 Personalised depression care ? 2. Clinical Profiling 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… Farmacogenetics as a candidate profiler for personalised care Psychiatric disorders are not restricted to the brain J Clin Psychiatry 2011 Arch Gen Psychiatry 2011, 65, 542-550 Arch Gen Psychiatry 1997 • • • • 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 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! 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 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 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 100 90 80 70 60 50 40 30 20 10 0 angst pijn alc bipo neurotic impuls metab hpa inflam chronob seizon trauma event family suic
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