Au-delà Du DSM-5 - Douglas

Au-delà du DSM-5Serge Beaulieu, M.D., Ph.D., FRCPCChef médicalProgramme des troubles de l'humeur, d'anxiété etd'impulsivité et Programme des troubles bipolaires,Institut DouglasDirecteur médicalActivités cliniques, du transfert des connaissances etde l'enseignement, Institut DouglasProfesseur agrégéDépartement de psychiatrie, Université McGill

DisclosuresSpeaker bureau:Bristol Myers Squibb (BMS)Janssen-OrthoOryxAstra ZenecaEli LillyLundbeckOtsukaBiovailGlaxoSmithKline (GSK)OrganonWyeth PfizerConsultant/Advisory Board:Eli LillyLundbeckOtsukaAstra ZenecaGlaxoSmithKline (GSK)MerckBristol Myers Squibb(BMS)Janssen-OrthoPfizerPeer-Reviewed Funding:NARSADCIHRRSMQFRSQSTANLEY FOUNDATIONResearch Support & Contract:Bristol Myers Squibb (BMS)LundbeckPfizerStock holding/patents:N/AAstra ZenecaEli isOtsuka

Identification of risk loci with shared effects on fivemajor psychiatric disorders: a genome-wide analysisCross-Disorder Group of the Psychiatric Genomics ConsortiumThe Lancet - 28 February 2013

Association results andforest plots showing effectsize for genome-widesignificant loci by disorderData in parentheses arenumbers of cases orcontrols. Het p p valuefor the heterogeneity test.Het I heterogeneity teststatistic. IQS imputationquality score (INFO).ln(OR) log of the oddsratio (OR). F frequency.SE standard error of thelog OR. ADHD attentiondeficit-hyperactivitydisorder. ASD autismspectrum disorders.BPD bipolar disorder.MDD major depressivedisorder. *Number ofstudies in which the variantwas directly genotyped.

“Mixed Depression” or “Depressive Mixed States”STEP-BD: Presence of sub-syndromal mania (1-3 mania symptoms)is frequent during index bipolar MDENoManiaPercent of Patients35 (31.2%)30Subsyndromal Mania(54.0%)2520Full Mixed Episode(14.8%)15105001234567Number of DSM-IV Manic SymptomsGoldberg et al. Am J Psychiatry 2009; 166: 173-81.

Longitudinal Course of Bipolar Disorder Prospective follow-up of 219 BDI patients– 122 (56%) followed for 20 years 1208 episodes observed– Only 2 pure mixed episodes ( 1%) Defined as concurrent depression and mood elevation throughout theentire episode– 94 episodes (8%) of “mixed major cycling” Episode of major cycling that at some point included a mixed state ofconcurrent depression and mood elevationSolomon DA, et al. Arch Gen Psychiatry 2010: 67: 339-47.

Mixed States:Diagnostic Complexities There is concordance among many researchers that mixedstates are not simply a simultaneous or sequential occurrenceof affective symptoms of opposite polarity, i.e., depression andmania, but rather complex, fluctuating and unstable clinicalpictures1 This may not be captured by DSM-IV criteria alone whichoperationalizes mixed states as a stable construct. Mixed states may be better defined along acontinuum/spectrum (consistent with clinical practice) asopposed to being a static/modal phenomenon The “degree of mixity” becomes the operational term1. Kruger S, et al. Bipolar Disorders 2005: 7: 205-215.

DSM 5Bipolar Disorders ClassificationOctober 2012CCCCCC000102030405Bipolar I DisorderBipolar II DisorderCyclothymic DisorderSubstance-Induced Bipolar DisorderBipolar Disorder Associated with Another Medical ConditionBipolar Disorder Not Elsewhere ClassifiedSpecifiers:Current or Most Recent Episode Hypomanic/ManicCurrent or Most Recent Episode DepressedWith Mixed FeaturesWith Psychotic Features (for depression)With Catatonic Features (for depression)With Atypical Features (for depression)With Melancholic Features (for depression)With Rapid CyclingWith Anxiety, mild to severeWith Suicide Risk SeverityWith Seasonal PatternWith Postpartum Onset

DSM 5Proposed revision onBipolar Disorder diagnostic category (2/3)October 2012Bipolar Disorder not Elsewhere Classified(NEC)- Subclassification will be used for this diverse group ofconditions.- The recorded name of the condition should NOT be“Bipolar Disorder NEC” but rater, one of the followingdiagnostic terms:- MDEs & Short (2-3) Hypomanic Episodes- MDEs & Hypomanic Episodes characterized by insufficientsymptoms- Hypomanic Episode witout MDE- Short Duration (less than 2 years) Cyclothymia- * Uncertain Bipolar Condtions

Proposed ICD – 11Mood Disorders ClassificationF30 First manic episodeF31 Bipolar affective disorderF32 First depressive episodeF33 Recurrent depressive disorderF34 First mixed affective episodeF35 Persistent mood disordersF38 Other mood disordersF39 Unspecified mood disorders

Three-Fold Higher Rate of Bipolar Disorder AmongstIndividuals with MDD When Using Bipolar SpecifierAngst J. et al. Arch Gen Psychiatry. 2011;68(8):791-799.

Patients With Mixed Episodes Have Poor TreatmentOutcomes More severe course of illness1,2 Less frequent remission/higher riskof reoccurrence1,2 More substance abuse1,2 Poorer response to some medications2 Increased risk of suicide3,41. Shah NN, et al. Psychiatr Q. 2004;75(2):183-196. 3. Hirschfeld RMA, et al. J Clin Psychiatry. 2003;64(1):53-59.2. Prien RF, et al. J Affect Disord. 1988;15(1):9-15. 4. Goldberg JF, et al. J Affect Disord. 1999;56(1):75-81.

Comorbidity is the rule, notthe exception Many possible combinationsof comorbidities Few high quality studies toguide treatment decisions Clinicians still requestguidance for treatmentoptionsComorbid DSM-IVDisorderComorbid ChronicPhysical DisorderMajor Depression62%72%Bipolar Disorder88%59%Merikangas et al, 2011; Kessler et al, 2010; Magalhaes et al, 2011.

CANMAT Clinical GuidelinesBipolar RevisionDepression Revision2005, 2007, 2009 et 20132009CANMAT Task Force Recommendations for MoodDisorders and Comorbid Conditions– Roger McIntyre, Ayal Schaffer, Serge Beaulieu– Published February, 2012– Anxiety, medical, personality, substance use, ADHD,metabolic syndrome– Available at www.canmat.org

Arguments en faveur d’une classification dimensionnelle“ Nearly all genetic factors identified thus far seem toconfer somewhat comparable risk for schizophrenia andbipolar disorder and, perhaps, for other disorders such asunipolar depression, substance abuse, and even epilepsy.”“ the biology of psychotic illnesses mayfail to align neatly with the classic Kraepelinian distinctionbetween schizophrenia and manic-depressive illness However, they do resonate with clinical observations thatmany patients present with a mix of bipolar andschizophrenia symptoms, both at a single admission and alsoacross time.”B.N. Cuthbert and T.R Insel. Schizophrenia Bulletin. 2010. 36 (6): 1061-1062.

Arguments en faveur d’une classification dimensionnelle“These clinical observations support theaccelerating body of literature over the last decadearguing that Kraepelin’s classic dichotomy for psychoticdisorders may need to be superseded by a new systembased on biology as well as observed clinicalphenomenology.”B.N. Cuthbert and T.R Insel. Schizophrenia Bulletin. 2010. 36 (6): 1061-1062.

Research Domain Criteria

Approche Dimensionnelle:“The Good, the Bad and the Ugly”In many of the results of randomized clinical trials orof risk studies that use categorical measures, areport of statistical non-significance may be partiallyor wholly due to the lack of power to detect effectsdue to use of categorical measures, particularlywhen the cutoff defining the categorical measures isset by intuition rather than optimally based onempirical evidence.Kraemer, HC. Int J. Methods in Psych. Res. 2007. 16 (S1): S8-S15.

Approche Dimensionnelle:“The Good, the Bad and the Ugly” Approche empirique Permet des analyses statistiques plus ciblées sur lesmodérateurs et médiateurs donc plus en harmonie avec lesstratifications cliniques Rapprochement avec les symptômes cliniques observéspar les cliniciens et vécus par les patients Pourrait donc éventuellement créer une classification plusécologiquement valideKraemer, HC. Int J. Methods in Psych. Res. 2007. 16 (S1): S8-S15.

Approche Dimensionnelle:“The Good, the Bad and the Ugly” Meilleure modélisation de la psychopathologiedans des modèles animaux Approche qui favorise l’étude de l’aspectdévelopmental des maladies

Approche Dimensionnelle:“The Good, the Bad and the Ugly” Faibles validités inter-juges (Kappa ratings) obtenueslors des essais en milieux cliniques (mêmeacadémiques) Dépression: 0.34 !!!!

Approche Dimensionnelle:“The Good, the Bad and the Ugly” Risquons de devoir redéfinir l’ensemble des traitements enfonction des nouveaux critères

Au-delà du DSM-5 Serge Beaulieu, M.D., Ph.D., FRCPC Chef médical Programme des troubles de l'humeur, d'anxiété et d'impulsivité et Programme des troubles bipolaires, Institut Douglas Directeur médical Activités cliniques, du transfert des connaissances et de l'enseignement, Institut Douglas Professeur agrégé