OverviewofClinicalSymptomsandTreatmentinEarlyPsychosis

ChristianKohler,MD

WhatisPsychosis?Alterationinrealitytestingmanifestedbyeither•  Hallucinations•  Delusions•  Disorganizedbehavior•  Disorganizedspeech

Plus•  Impairedfunctioning

DopamineHypothesis:basedonmedeffects,drugs,animalmodels -mesolimbichyperactivity -mesocorticalhypoactivity

DopamineHypothesis:basedonmedeffects,drugs,animalmodels

ConsiderationsinEarlyPsychosis•  HeterogeneityofSymptoms•  MedicationEffectsandSide-effects•  Insight/WillingnessforTreatment•  DrugUse•  Effectofdurationofuntreated/persistentpsychosis•  FamilyUnit•  Social-occupationalFunctioning

IdentifyingAt-RiskIndividuals(mild/warningsignsofpsychosis)

IdentifyingAt-RiskIndividualsPrevalenceofmildsignsofpsychosis(ClinicalRisk)Childhood(ages9-12)~17%Adolescence(ages13-18)~7.5%Prodromal(AttenuatedPsychosisSyndromeorClinicalHighRisk)Ages16-30+~2-3%Conversionratesfromprodromaltopsychosis•  ~20%over1year•  ~30%over2years•  ~35%remissionover5years•  ~40%persistence

Psychiatric Disorders with Psychosis

Schizophrenia

BriefPsychoticEpisode

Schizophreniform

SchizoaffectiveDisorder

BipolarDisorder

MajorDepression

Prodrome

LongerDurationUntreatedPsychosiscorrelateswith•  increasednegativesymptoms•  poorermedicationresponse•  reducedsymptomaticandfunctionalrecovery

WHOrecommendsDUP<3monthsManyyoungpersonsexperienceDUPof1yearandlongerbeforetreatmentRemissioninFEP:40-60%over1-2yearsLackofsignificantclinicalresponsewithin1-2yearstreatmentassociatedwithlowchanceofremission

WhatisatStake?~100,000youngAmericansexperienceFEPeachyearLifetimeprevalenceofschizophrenia~1%Pointprevalence~0.8%AfterFEPwithDx:schizophrenia•  <20%ofindividualsachievefullrecoverywithroutinecare•  80-90%areunemployed•  20%arehomeless•  23%areincarcerated•  ~10%completesuicide,oftenearlyintheirillnesses•  EconomicburdenofschizophreniaintheUnitedStatesestimated

at$155billionannually(2013)

•  Estimated23millionpeopleworldwide

Causes: Genetic RiskTo Date: 108 risk genes for schizophrenia

Causes: Environmental Factors

Adapted from Knowles, 2004

More Recent Clinical Risk and Early Psychosis Strategy

WhataresomecommonDifferentialDiagnosestobeconsidered?Drugs:

temporary:cocaine,ecstasy,LSD,amphetamines,spice/K2longerlasting:PCP,bathsalts/syntheticcathinonesinductioneffect?:THC

differentiatingfactors-shorterduration-negativesymptoms-activation-confusion

Comorbidityofschizophreniaanddrugabuse- 50%lifetimerate- 30%overpast6months(THC,cocaine,alcohol)

NeurologicalDisorders•  Epilepsy:TLE,primarygeneralized,TuberousSclerosis•  SpaceOccupyingLesions•  Dementias

SystemicIllnesses:•  Infections,e.g.syphilis,HIV,sarcoid/TB •  Hormonal,e.g.Thyroid,Cushing’sdisease•  ImmuneDisorders,e.g.SLE,paraneoplastic,NMDA-Rantibody

encephalitis,Hashimotothyroiditis•  GeneticDisorders,e.g.velocardiofacialsyndrome(22q11.2deletion

syndrome),Turnersyndrome,hemochromatosis,BGcalcifications,etc.

•  Storage:Wilson’sdisease,juvenile/adultmetachromaticleukodystrophy

Whatisareasonablework-uptoconsider?(Freudenreich 2007)

Whatisareasonablework-uptoconsider?DiagnosticTesting:MRIsin152FEpatients(Lubman2002)2casesofothermedicalcondition22%incidentalabnormalities76%normal1400youths(8-23yrs)underwentMRIsthroughCHOP(Gur2013)10.6%incidentalfindings1%clinicallysignificant

Whatisareasonablework-uptoconsider?DiagnosticTesting:EEGMayoClinicStudy:122FEpatients(Manchada2005)39%normal44%intermediate17%clearlyabnormalQuestionablediagnosticsignificancePrognosticvalueforremissionafter1yearNormalEEG:90%remissionversus55-60%

First-episodePsychosisTreatment

Ø  Bestchancesofresponse/recoveryØ  LackofeffectsofchronicillnessØ  Challengeofillnessacceptance

Durationofuntreatedpsychosisleadstoincreased

Ø Negativesymptomsî

Ø  Cognitivedysfunctionèassociatedwithfunctional

impairment

First-episodePsychosisTreatment

Ø About12First-episodestudiesinthelast40yearsØ 60-85%responseratesbasedonpositivesymptoms

Ø Timetoremission:mean=35weeks,median11weeks

Ø Nosuperiorityofnewermedications

Ø Relapserates60-80%Ø 80%associatedwithmedicationnonadherence(Robinson1999)

Ø DurationofUntreatedPsychosis:worseoutcome(Perkins2005)

DevelopmentofEarlyPsychosisProgramsMid-1980’s•  England•  Australia

1990’s•  Scandinavia•  Germany•  USA•  Canada~2000•  Japan•  China•  SouthEastAsia

RAISETrial(RecoveryAfterInitialSchizophreniaEpisode)34clinicsin21States,recruited2010-2012First-episodepsychosisregardlessofduration404patientsrandomizedtoCoordinatedSpecialtyCareModelversus“TreatmentasUsual”Ø  PersonalizedmedicationmanagementØ  ResiliencebasedpsychotherapyØ  Familypsychoeducation/therapyØ  SupportedemploymentAveage:23yrsM:F=2.5:170%livedwithfamilyDxofschizophreniaorschizophreniform:70%

Results:223patientsinCoordinatedSpecializedCare(CSC)65%completed2-yeartreatment,45%continuouscareThoseinCoordinatedSpecializedCareØ  experiencedgreaterimprovementinqualityoflife,including

interpersonalrelationships

Ø  remainedintreatmentlonger;lowerdosesofantipsychotics

Ø  experiencedgreaterrelieffromoverallsymptomsaswellasdepression

Ø  betterinvolvementinworkandschool

Ø  durationofillnessrepresentsmoderatoroftreatmentresponse

Summary of 8 RCT (n=1200) of Early Psychosis Interventions comparing CSC versus TAU demonstrated

-  6Studies:reducedpsychoticsymptomburden-  4Studies:higherretentionintreatmentwithCSC

-  3Studies:showedhigherrecoveryrates

-  3Studies:improvedpsychosocialfunctioning

-  3Studies:costeffectivenessdespitehigherutilization

-  2Studies:differentialeffectsdisappearedaftercompletionofactivetreatment

Consequences

Ø  Starting2013CongressallocatedfundstobedistributedthroughSAMSHAatthestatelevel(5%MHBG)dedicatedtotreatmentforthose“withearlyseriousmentalillness”

Ø  Evidence-BasedTreatmentsforFirstEpisodePsychosis:ComponentsofCoordinatedSpecialtyCare(CSC)

Ø  Implementedin28Statesin2015

Ø  Increasedfundingfor2017to10%anddisseminationinall50States

ExistencesinceSpring2015Over150evaluationsandenrolledAfterintakeevaluation•  Cognitivetherapyforpsychosis:recoveryoriented•  Medicationmanagement•  Employment/scholasticsupport•  Cognitiveremediation•  Familyeducation

Cognitivetherapyforpsychosis:recoveryorientedFocuson•  Earlyexperiencesthatsheaperson’sbeliefsystem

•  Reframingnegativeautomaticthoughts

•  Pursuingnewbehaviorstrategiestoimprovefunctioning

•  Heavyfocusonpersonalengagement(rapportbuilding,activation)

Medicationmanagement•  Antipsychoticmedications:oralorlongactinginjectibles•  Lowdosages•  Timeperiod1-2years•  Riskofrelapse

Employment/ScholasticSupport•  Careerprofile:pastemployment,schoolingandinterests•  Followupaboutjobsearches•  Interactwithacademicsettingsaboutsupport•  ReferraltoOfficeofVocationalRehabilitation

ConclusionsEarlypsychosispresentsasauniqueopportunityforinterventionDecreasingdurationofuntreatedpsychosisishighpriority(Consensusstatement:<3months)PreventionofchronicillnessanddisabilityComprehensiveSpecialtyCare:specializedinterventionservicesØ mayimprovesymptomsandclinicalcourseØ  increaseretentionintreatmentprogram

Ø  improvefunctionaloutcome

Ø  arecosteffective