Treatment of Major Depression In Adolescents - SFBUP · 2018-04-26 · treatment advised for major...
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Treatment of Major Depression In Adolescents Ian M Goodyer OBE MD FRCPsych FMedSci University of Cambridge
Transcript of Treatment of Major Depression In Adolescents - SFBUP · 2018-04-26 · treatment advised for major...
TreatmentofMajorDepressionInAdolescents
IanMGoodyerOBEMDFRCPsychFMedSciUniversityofCambridge
Depressedmood
Irritability/anger
Anhedonia
Weight/appetitedisturbanceSleepdisturbance
PsychomotordisturbanceFatigue,lackofenergy,tiredness
Self-perceptionsCognitivedisturbance
Suicide
DSM:UnipolarMajorDepression
mood+4(ormore)others
Psychoticfeatures
3-4symptoms(mild);5-6symptoms(moderate);7+symptoms(severe)plusimpairment
RandomisedControlledTrials:
• TreatmentofAdolescentdepressionStudy(TADS):2004.
• AdolescentDepressionandPsychotherapyTrial(ADAPT):2007.
• TreatmentofResistantDepressioninAdolescents(TORDIA):2008.
• Improvingmoodwithpsychotherapyandcognitivetherapy(IMPACT):2017.
TADS:RCTDesign
2084screened1008interviewed
549Baselineassessment
Fluoxetine+CBT107(92)
FluoxetineOnlyN=109(91)
CBTOnlyN=111(87)
MedicationPlacebo
N=112(89)
MarchetalJAMA2004;292:807-820
TADS: Adjusted Mean (SE) Scale Scores
MarchetalJAMA2004;292:807-820
% of patients in remission by treatment group
0
1020
3040
5060
7080
comb flux CBT Pillplacebo
% response CDRS-R
N439adolescentswithMD,12weekoutcomes
TADSOutcomes1YearofNaturalisticFollow-Up
MarchJetalAmericanJournalofPsychiatry2009;166:1141-1149
TADS: Summary
• TreatmentwithfluoxetinealoneorincombinationwithCBTacceleratestheresponse.
• AddingCBTtomedicationenhancesthesafetyofmedication.
• Takingbenefitsandharmsintoaccount,combinedtreatmentadvisedformajordepressioninadolescents
MarchJSetalArchGenPsychiatry.200764(10):1132-43.
ADAPT: Adolescent Depression and Psychotherapy Trial
510 NHS outpatients assessed
261excluded(109notdepressed,48DNA,39drugconcerns,38refused,6tooill,1previoustreatment,20other)
249:164hadabriefpsychosocialintervention2/3sessions
126 BII non-responders
211 research interview
208 randomised
85bypassedBII(34inCAMHS,29onSSRI,22urgentmedsrequired)
34improved,4refused
2 refused, 1 improved
104specialistclinicalcare+Fluoxetine20mg-60mg
104specialistclinicalcare+Fluoxetine20mg-60mg+CBT
Clinician Rated Depression Scale 55
6065
7075
0 6 12 28Weeks
SSRI CBT+SSRI
Averagetreatmenteffect=1.43,95%CI-0.71,+3.52,p=0.19
GoodyeretelBMJ.2007Jul21;335(7611):142
CDRS-R
Self Report Depression Symptoms- MFQ
1020
3040
0 6 12 28Weeks
SSRI CBT+SSRI
Averagetreatmenteffect=1.27,95%CI-1.26,+3.80,p=0.32
GoodyeretelBMJ.2007Jul21;335(7611):142
Clinical Global Impression Over Study Period
weeks
Maximumclinicalbenefitsmaynotbeseenuntil28weeksaftertreatmentbegins
GoodyerIMetal(2008)HealthTechnolAssess.12(14):iii-iv,ix-60
ADAPTSummary
• NoaddedvalueforCBTintreatingunipolardepressionoverandabovethatofspecialistclinicalcareandfluoxetine.
• Overalltreatmenteffectivenessat28weeksaround60%.
• Treatmentresistance–10%-20%
• PatientsintheTrialweremoderate-severelyill.
• Notaneffectivenesstrialforfluoxetine
Treatment resistant depressions
Brent DA et al: The TORDIA Study JAMA. 2008 February 27; 299(8):
901–913
TORDIA: RCT Design
334treatmentresistantpatientsnoresponseto
SSRIs@12weeks
DifferentSSRIparoxetine,citalopram,fluoxetine,20–40mgN=85
DifferentSSRI+CBTN=83
Venlafaxine(150–225mg)
N=83
Venlafaxine+CBTN=83
Clinical response 12 weeks post new treatment
42
44
46
48
50
52
54
56
New SSRI NS+CBT Venlaf Ven + CBT
CGI %
N=334@entry;N=223completion;ITTanalysis(LR):CBTp=0.03qualifiedbyasitexCBTinteractionp=0.003
Clickonimagetomagnify.
TORDIA:Clinicalresponse72weekspostnewtreatment
Responseapparentby6weeks.~30%-noremissionand25%relapse.
VitielloB,etalJClinPsychiatry.2011Mar;72(3):388-96
TordiaSummary
• TreatmentresistancetoanSSRIcanrespondtocombinationtherapysuchasanotherSSRI+CBT.
• Venlafaxinenotamedicationofchoice.
• Responsebyabout6weekswithlittlegainfromthen.
TreatmentofDepressedAdolescents2000-2018
• Severedepressionsoccurin1%-2%
• Nonremissionby12months~30%
• Treatmentnonresponserate~10%-20%
• Norobustclinicalorpsychosocialpredictorsoftreatmentresponse,resistanceorrecurrencerisk
• Lessgoodresponseinthosewith– ahistoryofchildhoodmaltreatment,– mildmaniaatpresentation,– currentdepressioninmothers.
ImprovingMoodWithPsychoanalyticPsychotherapyAndCognitiveBehaviour
Therapy:THEIMPACTSTUDY
TheIMPACTConsortiumIanMGoodyer
ChiefInvestigatorUniversityofCambridge
Whatwereourobjectives
• Whetherpsychologicaltreatmentwas‘goodenough’tomaintainreduceddepressivesymptoms12monthsaftertreatment.
• Ifsowouldthisbecosteffectiveaswellasclinicallyeffective.
• WouldspecialisttreatmentofCBTbesuperiortoshorttermpsychoanalytictherapy(STPP)inachievingtheobjectives.• WouldCBTand/orSTPPbesuperiortothereferencetreatmentofbriefpsychosocialintervention(BPI)
PrinciplesofBriefPsychosocialIntervention
• Collaborativecare.
• Informationexchange.
• Selectedbehaviouralactivation
• Rehabilitationandrecovery.
• Improvingandmaintainingmentalandphysicalhygiene,engaginginpleasurableactivities,maintainingschoolworkandpeerrelationsanddiminishingsolitariness.
ShortTermPsychoanalyticPsychotherapy
• Aimstoincreasethecoherenceoftheyoungperson’smentalmodelsofattachmentrelationships• Therebyimprovecapacityforaffectregulationandtherebythemakingandmaintainingofpositiverelationships.• Techniquesbasedontherelationshipwiththetherapist.
• Explorationofthe'internalworld’experiences:currentpreoccupations,memories,day-dreams,nocturnaldreamsandphantasies.
• Attendingtounconsciousphenomenaisspecifictopsychoanalyticpsychotherapy.
• Thepatient’sexperienceofthetherapistreceiving,holdinginmind,andthinkingaboutprojectedmaterialisacentralfeatureofthetherapy.
CognitiveBehaviourTherapy
• CognitiveBehaviourTherapy(CBT)isbasedontheclassicalformoriginallydevelopedforadultswithdepression.• Pervasiveinformationprocessingbiaseswhichincreasevulnerabilitytodepressioninthecontextofenvironmentalstress.• Thesebiasesmaintainandamplifycoremoodsymptomsofdepression.
• ThefocusofCBTistoidentifytheinformationprocessingbiasesthatmaintaindepressionandlowmoodandtoamendthesethroughaprocessofcollaborativeempiricismbetweenthetherapistandclient.• CBTwasadaptedforthisstudybyincreasingfocusonengagement,useofbehaviouraltechniquesandparentalinvolvement,
TherapyDuration
• BPI:12sessions,(8individual+4family/parent),over20weeks.
• STPP:28sessions(+7parentsessions)over28weeks.
• CBT:Upto20sessionsover30weeks(parentinvolvementifindicated).
ProfessionalsDeliveringTherapy
BPI:ChildandAdolescentPsychiatrists(80%)includingFellowsandChildandAdolescentMentalHealthNurses(20%).CBT:Clinicalpsychologistsorotherprofessionalswithpostqualification
traininginCBTSTPP:Child/AdolescentPsychotherapistsandtraineesintheirlastyear.
Design
ReassessmentsAtthenominal6,12,3652and86week
MDDN=470
BPI12sessions/20weeks
N=155Endofstudy=132
CognitiveBehaviourTherapy20sessions/20weeks
N=154Endofstudy=130
STPP28sessions/30weeks
N=156Endofstudy=119
RandomisedtoOneof3Treatmentarms
MR-IMPACTME-IMPACTGeneticAssayCognitiveAssayCortisolAssay
GoodyerIMetalTrials.2011Jul13;12:175
ParticipantCharacteristics
Characteristic BPI(n=155)Freq.(%)
CBT(n=154)Freq.(%)
STPP(n=156)Freq.(%)
MeanAgeinyrs15.6(1.4) 15.6(1.4) 15.6(1.5)
Females115(74) 114(74) 119(76)
White121(82) 131(86) 130(86)
SSRIbeforetrialentry29(19) 32(21) 28(18)
Mean(MFQ)depressionscore 46.2(10.6) 46.2(10.3) 45.4(10.8)
Interviewerratedsymptoms8.4(2.5) 8.7(2.3) 3. (2.5)
PsychosocialimpairmentScale18.9(6.0) 18.4(6.0) 18.3(6.3)
ParticipantCharacteristicsatBaseline
Characteristic BPI(n=155)Freq.(%)
CBT(n=154)Freq.(%)
STPP(n=156)Freq.(%)
RecentSelfharm26(17) 25(16) 34(22)
LifetimeSelfHarm87(56) 75(49) 84(54)
RecentSuicidalAttempts3(2) 2(1) 7(5)
LifetimeSuicideAttempts57(37) 48(31) 55(35)
Comorbidity(1+)71(46) 80(52) 74(47)
DisruptiveBehaviourDisorders20(13) 20(13) 16(10)
MedianTime(weeks)FromRandomisationToStartingTherapy
BPI CBT STPP
Region Median (95% c.i.) Median (95% c.i.) Median (95% CI)
East Anglia 4.3 (3.3 to 5.6) 7.3 (5.1 to 10.1) 4.7 (3.9 to 5.7)
North London 2.9 (2.0 to 3.7) 4.0 (3.0 to 4.7) 3.9 (2.7 to 4.4)
North West 4.0 (3.1 to 4.6) 4.0 (2.9 to 4.9) 4.4 (3.1 to 6.1)
DurationOfTherapyInWeeks
Treatment Med Max Mean SD N
BPI 22.1 111.9 27.5 21.5 130
CBT 23.1 99.6 24.9 17.7 130
STPP 30.1 97.0 27.9 16.8 131
BPI CBT STPPMedian(IQR)a 6 (4,11) 9 (5,14) 11 (5,23)
Planned 12 20 28
Numberoftherapysessionsattended
Treatmentdifferentiation0
12
34
5BPI CBT STTP
CB Domain PI Domain
CPPS
Doma
in Sc
ore
Graphs by Trial Arm
Measurestakenby2ratersindependentlylisteningtoafixedtimeseriesfrom279audiotapesrandomlyselectedfromthe3armsstratifiedbyage,centreandphaseoftherapy(early,2-4,later>4sessions).MeasuredusingtheCPPSreliability=0.82&0.8perscale.• CBT>STPPon(CB)sub-scalescore(95%CI1·73to2·09,p<0·0001).• STPP>CBTmeanon(PI)sub-scalescore(95%CI1·01to1·3,p<0·0001).• BPI<CBTonCBsub-scale(meandiff.=-0·93,95%CI-1·12to-0·75,p<0·0001)• BPI<STPPonthePIsub-scale(meandiff.=-1·30,95%CI-1·48to-1·11,p<0·0001).• 81%ofBPI,80%ofSTPPand74%ofCBTsessionsmetcriteria
PrevalenceofDepressiveSymptomsAtEntry
0
10
20
30
40
50
60
70
80
90
100
BPI
CBT
STPP
DepressionScoresOverTheStudy
0
5
10
15
20
25
30
35
40
45
50
Baseline 6week 12week 36week 52week 86week
BPI
CBT
STPP
Endoftreatment
MeanMFQ
Score
DepressionSumScoresOverTheStudy20
3040
50Sc
ore
0 20 40 60 80 100Weeks
BPI CBT STPP
ns
IndividualDifferencesinSymptomChange
AverageSymptomChangeovertime
IndividualSymptomChangeovertime
Individualdifferencesinsymptomchangeisevident
020
4060
MFQ
0 20 40 60 80Weeks
20
30
40
0 25 50 75Weeks
MFQ
Female Male
SuicideAttempts&NSSI
0
2
4
6
8
10
12
14
16
18
20
Baseline 6 12 36 52 86
SuicAtmpt
NSSI
Nobetweentreatmentgroupdifferences
SSRIPrescribingOverTheStudy
0
5
10
15
20
25
30
35
40
45
<36wk >=36wk
BPI
CBT
STPP
CostEffectivenessinUKPounds
0
500
1000
1500
2000
2500
3000
3500
Treatment FollowUp Total
BPI(n=90)
CBT(n=92)
STPP(n=91)
UKPo
unds
Summary
• TherearenosuperiorityeffectsofCBToverSTP.
• All3treatmentsarestatisticallyaseffectiveaseachother.
• Allthreetherapiesshowreducedsymptomsayearaftertreatment.
• BPIoffersanadditionalpatientchoiceforpsychologicaltherapy.
• Nocosteffectivenessadvantagebetweenthe3treatmentgroups.
Causality
• Cannotfullydiscountthepossibilitythatalltheobserveddeclineinsymptomsandimprovementinwell-beingwasafunctionoftime.
• Fluoxetinemayacceleratethedeclineinsymptomsacrossthecohortindependentofpsychologicaltreatment.
• Theabsenceofanotreatmentcontrolgrouplimitstheassertionthatanytherapywascausallyeffective.
ConfirmClinicallyDepressedAscertaindiagnosis,obtainselfreportsymptomscores
AssessPredictors/ModeratorsofLikelyTreatmentResponse1.Historyofchildhoodmaltreatment.2.Currentdepressioninaparent.3.Comorbiditiesatpresentation4.Expectationsoftreatment5.Complianceandresponsetopasttreatments.
CollaborativeDiscussion1.Entercollaborativediscussionwithpatientandfamilyaboutdepressionandtreatmentoptions.2.Explainaboutdepressionandanswerallrelevantquestions.3.Explaintreatmentoptionsincludingassociatedrisks.4.Getaplannedtherapeuticsprotocolagreedwithadolescent.5.Offeratimelineforfirstlinetreatment.
TherapeuticActivation1.Firstlinemonotherapycanbepsychological.2.Canbecombinationpsychosocial+fluoxetine.3.Complexcasesmayneedcombinationtherapywithfluoxetineasapriority+psychosocialtreatment.
Therapeuticreview:3-4weeks1. Ispatientalliedwiththerapistandtreatment2. Assessforsideeffects:considertreatment
reluctance,non-complianceandnon-attendanceaspossiblesignsofadverseeffectstotreatment.
3. Furthercollaborativediscussionaboutprogress.
4. Continueorrevisitcurrenttreatmentplan.
TreatmentProgress1. Someimprovementswithanytreatmentby6
weeks.2. 12-18weeksexpectremissioninabout50%
ofcases.3. By24-36weeksexpectremissioninafurther
20-30%.4. Expect10%-20%dropoutby12weeks.5. Expect10%-20%treatmentresistance.6. Noimprovementby6-12weeks-repeatboxD.
A
B
C
D
E
ClinicalAssessment,TreatmentandMonitoring
FutureResearch
• Treatmentresponse.
• Themaintenanceofpositiveeffects.
• Non-response.
• WhetherBPIisofutilityincommunityandprimarycaresettings.
• Fluoxetineeffects.
Acknowledgements
• ThisresearchwasfundedbytheNationalInstituteforHealthResearchHealthTechnologyAssessment(NIHRHTA)programme(projectnumber:06/05/01).
• TheviewsexpressedinthispublicationarethoseoftheauthorsanddonotnecessarilyreflectthoseoftheHTAprogramme,NIHR,NHS,ortheDepartmentofHealth.
• TheongoingresearchisfundedbytheWellcomeTrust,RoyalSocietyandFriendsofPeterhouse.
