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Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. PracticeParameterfortheAssessmentandTreatment ofChildrenandAdolescentsWith DepressiveDisorders ABSTRACT Thispracticeparameterdescribestheepidemiology,clinicalpicture,differentialdiagnosis,course,riskfactors,and pharmacologicalandpsychotherapytreatmentsofchildrenandadolescentswithmajordepressiveordysthymicdisorders. Sideeffectsoftheantidepressants,particularlytheriskofsuicidalideationandbehaviorsarediscussed.Recommen- dationsregardingtheassessmentandtheacute,continuation,andmaintenancetreatmentofthesedisordersarebased J.Am.Acad.ChildAdolesc.Psychiatry, 2007; 46(11):1503 Y 1526. KeyWords: majordepressivedisorder,dysthymicdisorder,evaluation,treatment,antidepressants, selectiveserotoninreuptakeinhibitors,psychotherapy,practiceparameter. Depressivedisordersareoftenfamilialrecurrentill- nessesassociatedwithincreasedpsychosocialmorbidity andmortality.Earlyidentificationandeffectivetreat- mentmayreducetheimpactofdepressiononthefamily, social,andacademicfunctioninginyouthsandmay tenceofdepressivedisordersintoadulthood.Evidence- supportedtreatmentinterventionshaveemergedin psychotherapyandmedicationtreatmentofchildhood depressivedisordersthatcanguideclinicianstoimprove outcomesinthispopulation. METHODOLOGY Thelistofreferencesforthisparameterwasdevel- opedbysearching PsycINFO , Medline ,and Psychological Abstracts ;byreviewingthebibliographiesofbook suggestedsourcematerials;andfromtheprevious versionofthisparameter(AmericanAcademyofChild andAdolescentPsychiatry,1998),therecentAmerican PsychiatricAssociation/AACAPguidelines B TheUse ofMedicationinTreatingChildhoodandAdolescent Depression:InformationforPhysicians [ published by ParentsMedGuide.org ,theAmericanPsychiatric Associationguidelinesforthetreatmentofadultswith MDD(AmericanPsychiatricAssociation,2000a; rithmsforthetreatmentofchildrenandadolescents withMDD(Hughesetal.,2007),andtheNational InstituteofHealthandClinicalExcellence(NICE; 2004)guidelinesforthetreatmentofdepressedyouths. Thesearches,conductedin2005,usedthefollowing textwords: B majordepressivedisorder, [B dysthymia, [ AcceptedJune7,2007. ThisparameterwasdevelopedbyBorisBirmaher,M.D.,andDavidBrent, M.D.,principalauthors,andtheAACAPWorkGrouponQualityIssues: andR.ScottBenson,M.D.,AllanChrisman,M.D.,TiffanyFarchione,M.D., LaurenceGreenhill,M.D.,JohnHamilton,M.D.,HeleneKeable,M.D.,Joan Kinlan,M.D.,UlrichSchoettle,M.D.,andSaundraStock,M.D.AACAPStaff: KristinKroegerPtakowskiandJenniferMedicus. Theauthorsacknowledgethefollowingexpertsfortheircontributionstothis parameter:JeffreyBridge,Ph.D.,AmyCheung,M.D.,GregClarke,Ph.D., GrahamEmslie,M.D.,PhilipHazell,M.D.,StanKutcher,M.D.,Laura Mufson,Ph.D.,KellyPosner,Ph.D.,JosephRey,M.D.,KarenWagner,M.D., andElizabethWeller,M.D. ThisparameterwasmadeavailableforreviewtotheentireAACAP membershipinFebruaryandMarch2006. ConsensusGroupconvenedbytheWorkGrouponQualityIssues.Consensus Groupmembersandtheirconstituentgroupswereasfollows:WorkGroupon QualityIssues(OscarBukstein,M.D.,HeleneKeable,M.D.,andJohn Hamilton,M.D.);TopicExperts(GrahamEmslie,M.D.,andGregClarke, Ph.D.);AACAPAssemblyofRegionalOrganizations(SyedNaqvi,M.D.);and AACAPCouncil(DavidDeMaso,M.D.,andMichaelHouston,M.D.). DisclosuresofpotentialconflictsofinterestforauthorsandWorkGroupchairs areprovidedattheendoftheparameter.Disclosuresofpotentialconflictsof interestforallotherindividualsnamedaboveareprovidedontheAACAPWeb siteonthePracticeInformationpage. 2007. ThispracticeparameterisavailableontheInternet(www.aacap.org). ReprintrequeststotheAACAPCommunicationsDepartment,3615 WisconsinAvenue,NW,Washington,DC20016. 0890-8567/07/4611-1503
2007bytheAmericanAcademyofChild andAdolescentPsychiatry. DOI:10.1097/chi.0b013e318145ae1c AACAPOFFICIALACTION 1503 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. antidepressants, [ and B psychotherapy [ (e.g.,interper- sonal,psychodynamic,cognitive)combinedwiththe word B child. [ Thesearchescoveredtheperiod1990to January2007andonlyarticlesthatincludeddepressive disorderswereincluded.Givenspacelimitations,we mainlycitedreviewarticlespublishedinrefereed journalsandaddednewrelevantarticlesnotincluded inthereviews. DEFINITIONS Theterminologyinthispracticeparameteris consistentwiththe DSM-IV-TR (AmericanPsychiatric Association,2000b).Unlessspecified,theterm B depression [ encompassesbothmajordepressivedis- order(MDD)anddysthmicdisorder(DD).Impair- mentmeansreducedfunctioninginoneormoremajor areasoflife(academicperformance,familyrelation- ships,andpeerinteractions). Theinformationincludedinthisparameterpertains mainlytoMDD.Therearefewclinicalstudiesandno controlledtrialsforthetreatmentofDDinyouths. However,basedonthelimitedadultliterature(Ameri- canPsychiatricAssociation,2000a),efficacioustreat- mentsforMDDmayalsobeusefulforthemanagement ofDD. Inthisparameter,unlessotherwisespecified,the terms B child [ and B youths, [ respectively,refertochil- drenandadolescents. B Parent [ referstoparentorlegal guardian. EPIDEMIOLOGY TheprevalenceofMDDisestimatedtobeapprox- imately2%inchildrenand4%to8%inadolescents, withamale-to-femaleratioof1:1duringchildhood and1:2duringadolescence(Birmaheretal.,1996).The riskofdepressionincreasesbyafactorof2to4after puberty,particularlyinfemales(Angoldetal.,1998), andthecumulativeincidencebyage18isapproximately 20%incommunitysamples(Lewinsohnetal.,1998). Approximately5%to10%ofchildrenandadoles- centshavesubsyndromalsymptomsofMDD.These youthshaveconsiderablepsychosocialimpairment, highfamilyloadingfordepression,andanincreased riskofsuicideanddevelopingMDD(Fergussonetal., 2005;Gonzales-Tejeraetal.,2005;Lewinsohnetal., 2000;Pineetal.,1998).Thefewepidemiological studiesonDDhavereportedaprevalenceof0.6%to 1.7%inchildrenand1.6%to8.0%inadolescents (Birmaheretal.,1996). Studiesinadultsandonestudyinyouthshave suggestedthateachsuccessivegenerationsince1940is atgreaterriskofdevelopingdepressivedisordersand thatthesedisordershavetheironsetatayoungerage (Birmaheretal.,1996). CLINICALPRESENTATION Clinicaldepressionmanifestsasaspectrumdisorder withsymptomsrangingfromsubsyndromaltosyn- dromal.Tobediagnosedwithasyndromaldisorder (MDD),achildoradolescentmusthaveatleast2 weeksofpersistentchangeinmoodmanifestedby eitherdepressedorirritablemoodand/orlossofinterest andpleasureplusagroupofothersymptomsincluding wishingtobedead,suicidalideationorattempts; increasedordecreasedappetite,weight,orsleep;and decreasedactivity,concentration,energy,orself-worth orexaggeratedguilt(AmericanPsychiatricAssociation, 2000b;WorldHealthOrganization,1992).These symptomsmustrepresentachangefrompreviousfunc- tioningandproduceimpairmentinrelationshipsorin performanceofactivities.Furthermore,symptoms mustnotbeattributableonlytosubstanceabuse,use ofmedications,otherpsychiatricillness,bereavement, ormedicalillness. Overall,theclinicalpictureofMDDinchildrenand adolescentsissimilartotheclinicalpictureinadults, buttherearesomedifferencesthatcanbeattributed tothechild _ sphysical,emotional,cognitive,andsocial developmentalstages(Birmaheretal.,1996;Fergusson etal.,2005;Kaufmanetal.,2001;Kleinetal.,2005; Lewinsohnetal.,2003a;Lubyetal.,2004;Yorbik etal.,2004).Forexample,childrenmayhavemood lability,irritability,lowfrustrationtolerance,temper tantrums,somaticcomplaints,and/orsocialwithdrawal insteadofverbalizingfeelingsofdepression.Also, childrentendtohavefewermelancholicsymptoms, delusions,andsuicideattemptsthandepressedadults. TherearedifferentsubtypesofMDD,whichmay haveprognosticandtreatmentimplications.Psychotic depressionhasbeenassociatedwithfamilyhistoryof bipolarandpsychoticdepression(Haleyetal.,1988; Stroberetal.,1993),moreseveredepression,greater long-termmorbidity,resistancetoantidepressantmono- therapy,and,mostnotably,increasedriskofbipolar AACAPPRACTICEPARAMETERS 1504 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. disorder(StroberandCarlson,1982).MDDcanbe manifestedwithatypicalsymptomssuchasincreased reactivitytorejection,le thargy(leadenparalysis), increasedappetite,cravingforcarbohydrates,and hypersomnia(Stewartetal.,1993;Williamsonetal., 2000).Youthswithseasonalaffectivedisorder(SAD; Swedoetal.,1995)mainlyhavesymptomsofdepression duringtheseasonwithlessdaylight.SADshouldbe differentiatedfromdepressiontriggeredbyschoolstress becausebothusuallycoincidewiththeschoolcalendar. DDconsistsofapersistent,long-termchangein moodthatgenerallyislessintensebutmorechronic thaninMDD.Asaconsequence,DDisoftenover- lookedormisdiagnosed.Althoughthesymptomsof dysthymiaarenotassevereasinMDD,theycauseas muchormorepsychosocialimpairment(Kovacsetal., 1994;Masietal.,2001).Fora DSM-IV diagnosisof DD,achildmusthavedepressedmoodorirritability onmostdaysformostofthedayforaperiodof1year, aswellastwoothersymptomsfromagroupincluding changesinappetiteorweightandchangesinsleep; problemswithdecision-makingorconcentration;and lowself-esteem,energy,andhope(AmericanPsychia- tricAssociation,2000b). COMORBIDITY BothMDDandDDareusuallyaccompaniedbyother psychiatricandmedicalconditions,andoftentheyoccur together(theso-calleddoubledepression).Dependingon thesettingandsourceofreferral,40%to90%ofyouths withdepressivedisorderalsohaveotherpsychiatric disorders,withupto50%havingtwoormorecomorbid diagnoses.Themostfrequentcomorbiddiagnosesare anxietydisorders,followedbydisruptivedisorders, attention-deficit/hyperactivitydisorder(ADHD),and, inadolescents,substanceusedisorders.MDDandDD usuallymanifestaftertheonsetofotherpsychiatric disorders(e.g.,anxiety),butdepressionalsoincreasesthe riskofthedevelopmentofnonmoodpsychiatric problemssuchasconductandsubstanceabusedisorders (Angoldetal.,1999;Birmaheretal.,1996;Fombonne etal.,2001a,b;Lewinsohnetal.,1998,2003a;Rohde etal.,1991). DIFFERENTIALDIAGNOSIS Severalpsychiatric(e.g.,anxiety,dysthymia,ADHD, oppositionaldefiantdisorder,pervasivedevelopmental disorder,substanceabuse)andmedicaldisorders(e.g., hypothyroidism,mononucleosis,anemia,certaincan- cers,autoimmunediseases,premenstrualdysphoric disorder,chronicfatiguesyndrome)aswellascondi- tionssuchasbereavementanddepressivereactionsto stressors(adjustmentdisorder)mayco-occurwithor mimicMDDorDD.Theseconditionsmaycausepoor self-esteemordemoralization,butshouldnotbediag- nosedasMDDorDDunlesstheymeetcriteriaforthese disorders.Moreover,thesymptomsoftheabove-noted conditionsmayoverlapwiththesymptomsofdepres- sion(e.g.,tiredness,poorconcentration,sleepand appetitedisturbances),makingthedifferentialdiagnosis complicated.Also,medications(e.g.,stimulants,corti- costeroids,contraceptives)caninducedepression-like symptomatology.ThediagnosisofMDDorDDcanbe madeifdepressivesymptomsarenotduesolelytothe illnessesorthemedicationsandifthechildfulfillsthe criteriaforthesedepressivedisorders. Becausemostchildrenandadolescentspresenting totreatmentareexperiencingtheirfirstepisodeof depression,itisdifficulttodifferentiatewhethertheir depressionispartofunipolarmajordepressionorthe depressivephaseofbipolardisorder.Certainindicators suchashighfamilyloadingforbipolardisorder,psy- chosis,andhistoryofpharmacologicallyinducedmania orhypomaniamayheraldthedevelopmentofbipolar disorder(Birmaheretal.,1996).Itisimportantto evaluatecarefullyforthepresenceofsubtleorshort- durationhypomanicsymptomsbecausethesesymptoms oftenareoverlookedandthesechildrenandadolescents maybemorelikelytobecomemanicwhentreatedwith antidepressantmedications(Martinetal.,2004).Itis alsoimportanttonotethatnotallchildrenwhobecome activatedorhypomanicwhilereceivingantidepressants havebipolardisorder(Wilensetal.,1998). CLINICALCOURSE Themediandurationofamajordepressiveepisode forclinicallyreferredyouthsisabout8monthsandfor communitysamples,about1to2months.Although mostchildrenandadolescentsrecoverfromtheirfirst depressiveepisode,longitudinalstudiesofbothclinical andcommunitysamplesofdepressedyouthshave shownthattheprobabilityofrecurrencereaches20%to 60%by1to2yearsafterremissionandclimbsto70% after5years(Birmaheretal.,2002;Costelloetal., DEPRESSIVEDISORDERS 1505 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. 2002).Recurrencescanpersistthroughoutlife,anda substantialproportionofchildrenandadolescentswith MDDwillcontinuetosufferMDDduringadulthood. Moreover,between20%and40%willdevelopbipolar disorder,particularlyiftheyhavetheriskfactors describedabove(Gelleretal.,1994;Stroberand Carlson,1982). Childhooddepression,comparedwithadult-onset depression,appearstobemoreheterogeneous.Some childrenmayhaveastrongfamilyhistoryofmood disordersandhighriskofrecurrences,whereasothers maydevelopbipolardisorderorbemorelikelyto developbehaviorproblemsandsubstanceabusethan depression(Birmaheretal.,2002;Fombonneetal., 2001a,b;Harrington,2001;Weissmanetal.,1999). Althoughtherearesomedifferences,forthemostpart thepredictorsofrecovery,relapse,andrecurrenceover- lap.Ingeneral,greaterseverity,chronicity,ormultiple recurrentepisodes,comorbidity,hopelessness,presence ofresidualsubsyndromalsymptoms,negativecognitive style,familyproblems,lowsocioeconomicstatus,and exposuretoongoingnegativeevents(abuse,family conflict)areassociatedwithpooroutcome(Birmaher etal.,2002;Lewinsohnetal.,1998). ChildhoodDDhasaprotractedcourse,withamean episodelengthofapproximately3to4yearsforclinical andcommunitysamples,andisassociatedwithan increasedriskofsubsequentMDDandsubstanceuse disorders(Kleinetal.,1988;Kovacsetal.,1994; Lewinsohnetal.,1991). COMPLICATIONS Ifuntreated,MDDmayaffectthedevelopmentof achild _ semotional,cognitive,andsocialskillsand mayinterfereconsiderablywithfamilyrelationships (Birmaheretal.,1996,2002;Lewinsohnetal.,2003b). Suicideattemptsandcompletionareamongthemost significantanddevastatingsequelaeofMDDwith approximately60%reporthavingthoughtaboutsuicide and30%actuallyattemptsuicide(AmericanAcademy ofChildandAdolescentPsychiatry,2001;Brentetal., 1999;Gouldetal.,1998).Theriskofsuicidalbehavior increasesifthereisahistoryofsuicideattempts,co- morbidpsychiatricdisorders(e.g.,disruptivedisorders, substanceabuse),impulsivityandaggression,availabil- ityoflethalagents(e.g.,firearms),exposuretonegative events(e.g.,physicalorsexualabuse,violence),anda familyhistoryofsuicidalbehavior(Beautrais,2000; Brentetal.,1988;Gouldetal.,1998). Childrenandadolescentswithdepressivedisorders arealsoathighriskofsubstanceabuse(includingnico- tinedependence),legalproblems,exposuretonegative lifeevents,physicalillness,earlypregnancy,andpoor work,academic,andpsychosocialfunctioning.After anacuteepisodeofdepression,aslowandgradual improvementinpsychosocialfunctioningmayoccur unlesstherearerelapsesorrecurrences.However,psy- chosocialdifficultiesfrequentlypersistaftertheremis- sionofthedepressiveepisode,underscoringtheneedfor continuingtreatmentforthedepressionaswellastreat- mentthataddressesassociatedpsychosocialandcon- textualissues(FergussonandWoodward,2002; Hammenetal.,2003,2004;Lewinsohnetal.,2003b). Inadditiontothedepressivedisorder,otherfactors suchascomorbidpsychopathology,physicalillness, poorfamilyfunctioning,parentalpsychopathology, lowsocioeconomicstatus,andexposuretonegativelife eventsmayaffectthepsychosocialfunctioningof depressedyouths(Birmaheretal.,1996;Fergusson andWoodward,2002;Lewinsohnetal.,1998,2003b). RISKFACTORS High-risk,adoption,andtwinstudieshaveshown thatMDDisafamilialdisorder,whichiscausedby theinteractionofgeneticandenvironmentalfactors (Birmaheretal.,1996;Caspietal.,2003;Kendler etal.,2005;Pilowskyetal.,2006;Pineetal.,1998; Reinherzetal.,2003;Weissmanetal.,2005,2006b). Infact,thesinglemostpredictivefactorassociated withtheriskofdevelopingMDDishighfamilyloading forthisdisorder(Nomuraetal.,2002;Weissman etal.,2005). Theonsetandrecurrencesofmajordepressionmay bemoderatedormediatedbythepresenceofstressors suchaslosses,abuse,neglect,andongoingconflictsand frustrations.However,theeffectsofthesestressorsalso dependonthechild _ snegativeattributionalstylesfor interpretingandcopingwithstress,support,andgenetic factors.Otherfactorssuchasthepresenceofcomorbid disorders(e.g.,anxiety,substanceabuse,ADHD,eating disorders),medicalillness(e.g.,diabetes),useofmedi- cations,biological,andsocioculturalfactorshavealso beenrelatedtothedevelopmentandmaintenanceof depressivesymptomatology(Caspietal.,2003;Costello AACAPPRACTICEPARAMETERS 1506 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. etal.,2002;GarberandHilsman,1992;Kaufmanetal., 2001;Kendleretal.,2005;Lewinsohnetal.,1998;Pine etal.,1998,2002,2004;Reyetal.,2004;Weissman etal.,2005;Williamsonetal.,1998). EVIDENCEBASEFORPRACTICEPARAMETERS TheAACAPdevelopsbothpatient-orientedand clinician-orientedpracticeparameters.Patient-oriented parametersproviderecommendationstoguideclini- cianstowardthebesttreatmentpractices.Treatment recommendationsarebasedbothonempiricalevidence andclinicalconsensusandaregradedaccordingto thestrengthoftheempiricalandclinicalsupport. Clinician-orientedparametersprovideclinicianswith theinformation(statedasprinciples)neededtodevelop practice-basedskills.Althoughempiricalevidencemaybe availabletosupportcertainprinciples,principlesare primarilybasedonexpertopinionandclinicalexperience. Inthisparameter,recommendationsforbesttreat- mentpracticesarestatedinaccordancewiththe strengthoftheunderlyingempiricaland/orclinical support,asfollows: € [MS] MinimalStandards areappliedtorecommen- dationsthatarebasedonrigorousempiricalevidence (e.g.,randomizedcontrolledtrials)and/orover- whelmingclinicalconsensus.Minimalstandards applymorethan95%ofthetime(i.e.,inalmost allcases). € [CG] ClinicalGuidelines areappliedtorecommen- dationsthatarebasedonstrongempiricalevidence (e.g.,non-randomizedcontrolledtrials)and/or strongclinicalconsensus.Clinicalguidelinesapply approximately75%ofthetime(i.e.,inmostcases). € [OP] Option isappliedtorecommendationsthat areacceptablebasedonemergingempiricalevidence (e.g.,uncontrolledtrialsorcaseseries/reports)or clinicalopinion,butlackstrongempiricalevidence and/orstrongclinicalconsensus. € [NE] NotEndorsed isappliedtopracticesthatare knowntobeineffectiveorcontraindicated. Thestrengthoftheempiricalevidenceisratedin descendingorderasfollows: € [rct] Randomizedcontrolledtrial isappliedtostudies inwhichsubjectsarerandomlyassignedtotwoor moretreatmentconditions € [ct] Controlledtrial isappliedtostudiesinwhich subjectsarenonrandomlyassignedtotwoormore treatmentconditions € [ut] Uncontrolledtrial isappliedtostudiesinwhich subjectsareassignedtoonetreatmentcondition € [cs] Caseseries/report isappliedtoacaseseriesora casereport CONFIDENTIALITY Recommendation1.TheClinicianShouldMaintaina ConfidentialRelationshipWiththeChildorAdolescent WhileDevelopingCollaborativeRelationshipsWith Parents,MedicalProviders,OtherMentalHealth Professionals,andAppropriateSchoolPersonnel[MS]. Attheoutsetoftheinitialcontact,theclinician shouldclarifywiththepatientandparentsthebound- ariesoftheconfidentialrelationshipthatwillbe provided.Thechild _ srighttoaconfidentialrelationship isdeterminedbylawthatvariesbystate.Eachstate hasmandatorychildabusereportingrequirements. Parentswillexpectinformationaboutthetreatment plan,thesafetyplan,andprogresstowardgoalsof treatment.Thechildshouldexpectthatsuicideor violenceriskissueswillbecommunicatedtotheparents. Theclinicianshouldrequestpermissiontocommunicate withmedicalproviders,othermentalhealthprofes- sionalsinvolvedinthetreatment,andappropriateschool personnel.Cliniciansshouldprovideamechanismfor parentstocommunicateconcernsaboutdeteriorationin functionandhigh-riskbehaviorssuchassuicidethreats orsubstanceuse. SCREENING Recommendation2.ThePsychiatricAssessmentof ChildrenandAdolescentsShouldRoutinelyInclude ScreeningQuestionsAboutDepressive Symptomatology[MS]. Cliniciansshouldscreenallchildrenandadolescents forkeydepressivesymptomsincludingdepressiveorsad mood,irritability,andanhedonia.Adiagnosisofade- pressivedisordershouldbeconsideredifthesesymptoms arepresentmostofthetime,affectthechild _ spsycho- socialfunctioning,andareaboveandbeyondwhatis expectedforthechronologicalandpsychologicalageof thechild.Toscreenfordepressivesymptoms,clinicians DEPRESSIVEDISORDERS 1507 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. couldusechecklistsderivedfromthe DSM or ICD-10 criteriafordepressivedisorders,clinician-basedinstru- ments,and/orchildandparentdepressionself-reports (AmericanAcademyofChildandAdolescentPsychiatry, 1997;Kleinetal.,2005;MyersandWinters,2002). EVALUATION Recommendation3.IftheScreeningIndicatesSignificant DepressiveSymptomatology,theClinicianShouldPerform aThoroughEvaluationtoDeterminethePresenceof DepressiveandOtherComorbidPsychiatricandMedical Disorders[MS]. Acomprehensivepsychiatricdiagnosticevaluationis thesinglemostusefultoolavailabletodiagnosede- pressivedisorders.Thepsychiatricassessmentofde- pressedchildrenandadolescentsmustbeperformed byadevelopmentallysensitiveclinicianwhoisableto achievegoodrapportwithchildren.Forexample, childrenmayeitherhavedifficultiesverbalizingtheir feelingsoralternativelydenythattheyaredepressed. Thus,theclinicianshouldalsobeattentivetoobservable manifestationsofdepressionsuchasirritability,changes insleephabits,declineinschoolperformance,and withdrawalfrompreviouspleasurableactivities. Cliniciansshouldevaluatethechild _ sandfamily _ s strengths.Also,theevaluationshouldbesensitiveto ethnic,cultural,andreligiouscharacteristicsofthechild andhisorherfamilythatmayinfluencethepresen- tation,description,orinterpretationofsymptomsand theapproachtotreatment. Theevaluationshouldincludedirectinterviewswith thechildandparents/caregiversand,ideally,withthe adolescentalone.Also,wheneverappropriate,other informantsincludingteachers,primarycarephysicians, socialservicesprofessionals,andpeersshouldbe interviewed.Subtypesofdepressivedisorders(seasonal, mania/hypomania,psychosis,subsyndromal,symp- tomsofdepression),comorbidpsychiatricdisorders, medicalillnesses,and(asindicated)physicalexamina- tionsandlaboratorytestsareamongtheareasthat shouldbeevaluated.Becauseoftheprognosticand treatmentimplications,asdescribedunderDifferential Diagnosisabove,itiscrucialtoevaluateforthepresence oflifetimemanicorhypomanicsymptoms. Severalstandardizedstructuredandsemistructured interviewsareavailablefortheevaluationofpsychiatric symptomsinchildrenolderthan7years(American AcademyofChildandAdolescentPsychiatry,1997; Kleinetal.,2005;MyersandWinters,2002)andmore recentlyinyoungerchildren(Lubyetal.,2003). However,manyoftheseinterviewsaretoolongtobe carriedoutinclinicalsettings,requirespecialtraining, andhavelowparent Y childagreement.Parents _ reports alsomaybeinfluencedbytheirownpsychopathology, highlightingtheimportanceofobtaininginformation notonlyfromparentsbutalsofromthechildandother sources,includingteachers. Intheassessmentoftheonsetandcourseofmood disorders,itishelpfultouseamooddiaryandamood timelinethatusesschoolyears,birthdays,andsoforth asanchors.Moodisratedfromveryhappytoverysad and/orveryirritabletononirritable,andnormativeand non-normativestressorsaswellastreatmentsarenoted. Themoodtimelinecanhelpchildrenandtheirparents tovisualizethecourseoftheirmoodandcomorbid conditions,identifyeventsthatmayhavetriggeredthe depression,andexaminetherelationshipbetween treatmentandresponse.Atpresent,nobiologicalor imagingtestsareclinicallyavailableforthediagnosisof depression. Evaluationofachild _ sfunctioningcanbedone throughtheuseofseveralratingscales(American AcademyofChildandAdolescentPsychiatry,1997; Wintersetal.,2005).Amongtheshortestandsimplest onesaretheChildren _ sGlobalAssessmentScale(Shaffer etal.,1983)andtheGlobalAssessmentofFunctioning (AmericanPsychiatricAssociation,2000b). Finally,theclinician,togetherwiththechildand parents,shouldevaluatetheappropriateintensityand restrictivenessofcare(e.g.,hospitalization).The decisionforthelevelofcarewilldependprimarilyon leveloffunctionandsafetytoselfandothers,which inturnaredeterminedbytheseverityofdepression, presenceofsuicidaland/orhomicidalsymptoms, psychosis,substancedependence,agitation,child _ s andparents _ adherencetotreatment,parentalpsycho- pathology,andfamilyenvironment. Recommendation4.TheEvaluationMustInclude AssessmentforthePresenceofHarmtoSelfor Others[MS]. Suicidalbehaviorexistsalongacontinuumfrom passivethoughtsofdeathtoaclearlydevelopedplan andintenttocarryoutthatplan(AmericanAcademyof ChildandAdolescentPsychiatry,2001;Gouldetal., AACAPPRACTICEPARAMETERS 1508 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. 1998).Becausedepressioniscloselyassociatedwith suicidalthoughtsandbehavior,itisimperativeto evaluatethesesymptomsattheinitialandsubsequent assessments(AmericanAcademyofChildandAdoles- centPsychiatry,2001;Gouldetal.,1998).Forthis purpose,lowburdentoolstotracksuicidalideationand behaviorsuchastheColumbia-SuicidalSeverityRating Scalecanbeused.Also,itiscrucialtoevaluatetherisk (e.g.,age,sex,stressors,comorbidconditions,hope- lessness,impulsivity)andprotectivefactors(e.g., religiousbelief,concernnottohurtfamily)thatmay influencethedesiretoattemptsuicide.Bothcurrent severityofsuicidalityandthemostseverepointof suicidalityinepisodeandlifetimeshouldbeassessed. Thepresenceofgunsinthehomeshouldbe ascertained,andtheclinicianshouldrecommendthat theparentssecureorremovethem(Brentetal.,1993b). Cliniciansshouldalsodifferentiatesuicidalbehavior fromothertypesofself-harmbehaviors,thegoalof whichistorelievenegativeaffect.Thistypeofbehavior mostcommonlyinvolvesrepetitiveself-cutting,with clearmotivationtorelieveanger,sadness,orloneliness ratherthantoendone _ slife. Homicidalbehaviorfollowsacontinuumsimilarto suicidality,fromfleetingthoughtsofhomicidetoideas withaplanandintent.Itisimportanttonotethat suicidalandhomicidalideationcanoccurinthesame individual;fullyonethirdofadolescentsuicidevictims inonestudyhadhomicidalideationintheweekbefore theirsuicide(Brentetal.,1993a).Theclinicianshould conductanassessmentsimilartothatdescribedfor suicidalideationwithregardtowhatfactorsare influencing,eitherpositivelyornegatively,thedegree oflikelihoodthepatientwillcarryoutahomicidalact. Asisthecaseforpatientsatriskforsuicidalbehavior, itisimportanttorestrictaccesstoanylethalagents, particularlyguns(Brentetal.,1993b). Recommendation5.TheEvaluationShouldAssessforthe PresenceofOngoingorPastExposuretoNegativeEvents, theEnvironmentInWhichDepressionIsDeveloping, Support,andFamilyPsychiatricHistory[MS]. Asnotedabove,depressionoftenresultsfroman interactionbetweendepressivediathesisandenviron- mentalstressors;thus,theneedforacarefulevaluationof currentandpaststressorssuchasphysicalandsexual abuse,ongoingintra-andextrafamilialconflicts,neglect, livinginpoorneighborhoods,andexposuretoviolence. Iftheabuseiscurrent,thenensuringthesafetyofthe patientisthefirstpriorityoftreatment.Itisalsoimpor- tanttoassessthesequelaeoftheexposuretonegative eventssuchasposttraumaticstressdisorder. Depressionoftenoccursinarecurringpattern involvingconflictwithpeers,parents,andotheradult authorityfiguressuchasteachers.Therelationship betweenconflictanddepressionisoftenbidirectional becausedepressioncanmakeapersonmoreirritable, whichthenincreasesinterpersonaltension,causing otherstodistancethemselvesfromthedepressed person,whichthenleadstoanexperienceonthepart ofthepatientoflonelinessandlackofsupport.An assessmentofthekeyrelationshipsinthepatient _ s socialnetworkisacriticalcomponenttotheimple- mentationofonetypeofpsychotherapyforadolescent depressionforwhichthereisevidenceofefficacy, namely,interpersonalpsychotherapy(IPT;Mufson etal.,2004).Involvementindeviantpeergroupsmay leadtoantisocialbehavior,generatingmorestressful lifeeventsandincreasingthelikelihoodofdepression (Fergussonetal.,2003). Thepresenceoffamilypsychopathologyshouldbe evaluatedtoassistinbothdiagnosisandtreatment becauseparentalpsychopathologycanaffectthechild _ s abilityandwillingnesstoparticipateintreatment,may bepredictiveofcourse(e.g.,bipolarfamilyhistory),and mayhaveaninfluenceontreatmentresponse.The clinicianshouldassessfordiscord,lackofattachment andsupport,andacontrollingrelationship(often referredtoas B affectionlesscontrol [ )becausethesecan berelatedtoriskforotherpsychiatricconditions suchassubstanceabuseandconductdisorderthatcan complicatethepresentationandcourseofdepression (Nomuraetal.,2002).Forfurtherinformation regardingassessmentofthefamily,refertothePractice ParameterfortheAssessmentoftheFamily(American AcademyofChildandAdolescentPsychiatry,2007). TREATMENT Recommendation6.TheTreatmentofDepressive DisordersShouldAlwaysIncludeanAcuteand ContinuationPhase;SomeChildrenMayAlsoRequire MaintenanceTreatment[MS]. Thetreatmentofdepressionisusuallydividedinto threephases:acute,continuation,andmaintenance. Themaingoaloftheacutephaseistoachieveresponse DEPRESSIVEDISORDERS 1509 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. andultimatelyfullsymptomaticremission.The followingarethedefinitionsofoutcome(Birmaher etal.,2000[ut];Emslieetal.,1998;Franketal.,1991): € Response :Nosymptomsorasignificantreductionin depressivesymptomsforatleast2weeks € Remission :Aperiodofatleast2weeksandmonths withnoorfewdepressivesymptoms € Recovery :Absenceofsignificantsymptomsofdepres- sion(e.g.,nomorethan1 Y 2symptoms)for Q 2 months € Relapse :A DSM episodeofdepressionduringthe periodofremission € Recurrence :Theemergenceofsymptomsofdepres- sionduringtheperiodofrecovery(anewepisode) Continuationtreatmentisrequiredforalldepressed youthstoconsolidatetheresponseduringtheacute phaseandavoidrelapses.Finally,maintenancetreat- mentisusedtoavoidrecurrencesinsomeyouthswho havehadamoresevere,recurrent,andchronicdisorder. Treatmentstrategiesforeachoneofthesethree treatmentphasesarediscussedindetailbelow.In general,thechoiceoftreatmentateachofthesephases shouldbegovernedbyfactorssuchasthesubject _ s ageandcognitivedevelopment,severityandsubtype ofdepression,chronicity,comorbidconditions,family psychiatrichistory,familyandsocialenvironment, familyandpatienttreatmentpreferenceandexpecta- tions,culturalissues,andavailabilityofexpertisein pharmacotherapyand/orpsychotherapy. Recommendation7.EachPhaseofTreatmentShould IncludePsychoeducation,SupportiveManagement,and FamilyandSchoolInvolvement[MS]. Psychoeducation. Psychoeducationreferstoeducation offamilymembersandthepatientaboutthecauses, symptoms,course,anddifferenttreatmentsofdepres- sionandtherisksassociatedwiththesetreatmentsas wellasnotreatmentatall.Educationshouldmakethe treatmentanddecision-makingprocesstransparentand shouldenlistparentandpatientascollaboratorsintheir owncare.Depressionispresentedasanillness,nota weakness,whichisnoone _ sfaultbuthasgeneticand environmentalcontributions.Thedifficultiesthatthe patientexperiencesinfunctionarenotmanipulation, butthemanifestationsofanillness.Thepatientand familyshouldbepreparedforwhatislikelytobea recurrentandoftenchronicillnessthatmayhavea prolongedperiodofrecovery.Thisenablesthepatient andfamilynottobeoverlydisappointedifrecoveryis prolonged,anditpreparesthemforthenecessityof continuationandadherencetotreatment.Parentsalso needguidanceabouthowtoparent:whentobestrict andwhentobelaxinlightoftheirchild _ sdepression. WrittenmaterialandreliableWebsitesaboutde- pressionanditstreatmentcanhelpparentsandtheir childtolearnaboutdepressionandmonitorthechild _ s progressand,ifthechildistakingmedications,poten- tialemergingsideeffects. Therearenocontrolledtrialsofpsychoeducation, butpsychoeducationseemstoimproveadherenceto treatmentandreducethesymptomsofdepression (Brentetal.,1993c[ut];Renaudetal.,1998[ut]).For familieswithdepressedparents,psychoeducationwith orwithoutfurtherinterventionshavealsoshowed improvementinhowfamiliesproblemsolvearound parentalillnessandchildren _ sbehaviorandattitudes (Beardsleeetal.,2003). SupportiveManagement. Inadditiontopsychoedu- cation,allsubjectsrequiresupportivepsychotherapeu- ticmanagement,whichmayincludeactivelistening andreflection,restorationofhope,problemsolving, copingskills,andstrategiesformaintainingparticipa- tionintreatment. FamilyInvolvement. Evenintheabsenceofformal familytherapy,itisvirtuallyimpossibletosuccessfully treatachildoradolescentpatientwithouttheclose involvementofparents.First,theclinicianhasto recognizethatmotivationfortreatmentcomesoften fromtheparents,andthereforethetreatmentcontract mustinvolvethem.Second,theparentsmayobserve aspectsofthechild _ sfunctioningorsymptomsthatthe childeitherisnotawareofordoesnotwishtoshare, andthisinformationisvitaltothedevelopmentofa realisticandeffectivetreatmentcontract.Third,the parentsareabletomonitortheirchild _ sprogressand serveasasafetynet. Asdescribedinthesectionaboutpsychotherapies (Recommendation9),despitethescarceandweak empiricalevidence,knowledgeofriskfactorssuggests thatinterventionswithfamiliesareanimportantpartof clinicalmanagement.Theseinterventionsshouldtake intoaccountthefamily _ sculturalandreligiousback- groundandfocusonstrengtheningtherelationship betweentheidentifiedpatientandcaregiver(s),provide AACAPPRACTICEPARAMETERS 1510 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. parentingguidance(e.g.,managementofconflicts), reducefamilydysfunction,andfacilitatetreatment referralforcaregiversorsiblingswithpsychiatric disordersandformaritalconflict(Asarnowetal., 1993[rct];Birmaheretal.,2000[ut];Diamondetal., 2002[ut];Garberetal.,2002;Hammenetal.,2004; Nomuraetal.,2002;Sanfordetal.,2006).Duringthe acutephaseoftreatment,especiallyifbothparentand childaredepressed,itmaybedifficulttodomuch productivefamilyworkwhenmultiplefamilymembers aredepressedandirritable.Familyworkthatis conductedaftersomesymptomaticreliefisstill importantbecauseparent Y childconflictisassociated notonlywithprolongationofdepressiveepisodesbut alsowithrelapseandrecurrence(Birmaheretal.,2000 [ut]). SchoolInvolvement. Schoolpersonnelalsoneed psychoeducationtohelpthemunderstandthedisease modelofdepression.Issuesrelatedtoconfidentiality alsoneedtobediscussed.Theclinician,alongwiththe family,shouldadvocateforsomeaccommodations (e.g.,schedule,workload)tothepatient _ scurrentdiffi- cultiesuntilrecoveryhasbeenachieved.Ifafterrecovery thechildcontinuestohaveacademicdifficulties,then oneshouldsuspectthatthereisstillsomesubsyndromal depressionorthatthereareothercomorbidconditions (e.g.,developmentallearningdisorders,ADHD,anxi- ety,substanceabuse)orenvironmentalfactorsthatmay explainthechild _ spersistentdifficulties. Studentswithadepressivedisordermayqualifyfor theEmotionalDisturbanceDisabilitycategorization undertheIndividualswithDisabilitiesEducationAct andthereforebeeligibletoreceiveschool-basedservices (e.g.,counseling)andaccommodationsthatenable themtocontinuetolearn(seePracticeParameterfor PsychiatricConsultationtoSchools,AmericanAcade- myofChildandAdolescentPsychiatry,2005). Recommendation8.Education,Support,andCase ManagementAppeartoBeSufficientTreatmentforthe ManagementofDepressedChildrenandAdolescentsWith anUncomplicatedorBriefDepressionorWithMild PsychosocialImpairment[CG]. ThecurrentacuteRCTswithpsychotherapyor pharmacotherapyhavereportedthatupto60%of childrenandadolescentswithMDDrespondtoplacebo (Bridgeetal.,2007[rct];Cheungetal.,2005[rct])and 15%to30%respondtobrieftreatment(Goodyer,etal., 2007[rct];Harringtonetal.,1998;Renaudetal.,1998 [ut]).Infact,supportivetreatment,comparedwith eithercognitive-behavioraltherapy(CBT)orIPT,is equallyefficaciousforthosewithmilddepression. Whenpatientsaremoreseverelydepressedandhave significantmelancholicsymptoms,hopelessness,or suicidalideation/behaviors,however,supportivetreat- mentisinferiortobothoftheseindicatedtherapies (Barbeetal.,2004a[rct];Marchetal.,2004[rct]; Mufsonetal.,1999[rct];Renaudetal.,1998[ut]). Thus,itisreasonable,inapatientwithamildorbrief depression,mildpsychosocialimpairment,andthe absenceofclinicallysignificantsuicidalityorpsychosis, tobegintreatmentwitheducation,support,andcase managementrelatedtoenvironmentalstressorsinthe familyandschool.Itisexpectedtoobserveresponse after4to6weeksofsupportivetherapy. Recommendation9.ForChildrenandAdolescentsWhoDo NotRespondtoSupportivePsychotherapyorWhoHave MoreComplicatedDepressions,aTrialWithSpecificTypes ofPsychotherapyand/orAntidepressantsIsIndicated[CG]. Inchildrenandadolescentswithmoderatetosevere depression,chronicorrecurrentdepression,consider- ablepsychosocialimpairment,suicidality,agitation, andpsychosis,supportivepsychotherapyandcase managementareusuallynotadequate.Forthese childrenandadolescentsinterventionswithmore specifictypesofpsychotherapiesorpharmacological treatmentsfordepressivedisordersareindicated. Asreviewedbelow,moderatedepressionmayrespond toCBTorIPTalone.Moreseveredepressiveepisodes willgenerallyrequiretreatmentwithantidepressants. Treatmentwithantidepressantsmaybeadministered aloneuntilthechildisamenabletopsychotherapyorif appropriate,theycanbecombinedwithpsychotherapy fromthebeginningoftreatment.Finally,depressed youthwhodonotrespondtopriormonotherapytreat- ment,eitherpsychotherapyorantidepressants,requirea combinationofthesetwotreatmentmodalities. Ingeneral,inadditiontoconsideringtheseverityand chronicityofthedepressivesymptoms,priorresponse totreatment,andotherfamilialandenvironmental factors,thedecisionaboutwhichtypeofmonotherapy tooffermaybedictatedbyavailabilityandpatientand familypreference.Forexample,childrenand/ortheir familiesmaynotwishtoparticipateinpsychotherapy ormayobjecttotakinganymedications.Specifictypes DEPRESSIVEDISORDERS 1511 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. ofpsychotherapiessuchasCBTorIPTmaynotbe available.Childrenmaynothaverespondedpreviously topsychotherapy(e.g.,6 Y 8weeksofCBTorIPT). Childrenmaybetooagitatedorpsychoticorhavelow motivation,poorconcentration,orsleepdisturbances toparticipateinpsychotherapyotherthansupportive treatmentpluspharmacotherapyuntiltheyarefeeling better,ortheymayhavedisorders(e.g.,autism,mental retardation)forwhichCBTorIPTmaynotbe appropriate. Theextantliteratureregardingtheacutepsychother- apyandpharmacologicaltreatmentsandtheirside effectsandclinicaluseforchildrenandadolescentswith depressivedisordersissummarizedbelow. Psychotherapy. Arecentrigorousmeta-analysisof35 RCTsfordepressedyouthsshowedthatalthoughsome studiesdemonstratedlargeeffects,overalltheeffectsof psychotherapyfortheacutetreatmentofdepressed youthsaremodest(Weiszetal.,2006).Treatments wereequallyefficaciousforchildrenandadolescents, individualandgrouppsychotherapy,samplesidentified ashavingdepressivedisordersversusdepressivesymp- tomatology,efficacyversuseffectivenessstudies,and whetherthestudiesusedcognitivetechniques(CBT)or otherapproaches(e.g.,IPT,behaviorproblem-solving, relaxation,attachment-basedtherapy).Outcomeswere significantlybetterwhentheinformantwastheyouth whencomparedwithhisorherparents,indicatingthe importanceofinterviewingbothchildrenandparents. Therewasnocorrelationbetweendurationoftreatment andresponse,suggestingthatbrieftreatmentsmaybe anefficaciousandeconomicalwaytotreatdepressed youths.However,thefewstudiesthatincludedfollow- upaftertheacutetreatmentshowedthatthebeneficial effectsofpsychotherapyappeardurablefortheinitial months,butnotfor1year.Thus,morestudiesare neededtoevaluatetheeffectsof B boosters [ andcon- tinuationtherapy.Onlysixstudiesassessedsuicidality asanoutcome.Onaverage,thesestudiesshoweda smallreductioninsuicidality,emphasizingtheneed formoretargettechniquestoaddressthisworrisome symptom.Finally,theeffectsofthepsychotherapyfor depressedyouthsalsoimprovedanxiety,butnotexter- nalizingsymptoms. Othermeta-analyseshavealsoshownthatCBTis effectiveforthetreatmentofyouthswithMDD (Comptonetal.,2004;Harringtonetal.,1998). CBTappearstobemoreefficaciouseveninthefaceof comorbidity,suicidalideation,andhopelessness,but whenthereisahistoryofsexualabuseorwhenoneof theparentsisdepressed,CBTdoesnotappearto performaswell(Barbeetal.,2004b[rct];Brentetal., 1998[rct];Lewinsohnetal.,1998;Melvinetal.,2006 [rct];Rohdeetal.,2004[rct]). InsharpcontrastwithmostCBTstudies(Weisz etal.,2006),arecentlargeRCTdidnotfind differencesbetweenCBTandplaceboforadolescents withMDD(Marchetal.,2004,2006b[rct]).More- over,althoughthecombinationofCBTandfluoxetine showedamorerapiddeclineindepressivesymptom reduction(Kratochviletal.,2006),ratesofclinical improvementandbaseline-adjustedsymptomratingsat endpointwerenotdifferentbetweencombination treatmentandmedicationalone.Also,thecombined treatmentwasbetterthanfluoxetinealonemainly forteenswithmildtomoderatedepressionandfor depressionwithhighlevelsofcognitivedistortion, butnotforseveredepression(Curryetal.,2006[rct]). Thecombinationtreatmentdidresultinagreaterrate ofremissionthaninanyoftheothertreatments,butthe effectsweremodest(remissionrateof37%in combinedtreatment;Kennardetal.,2006[rct]).Itis unclearwhyCBTdidnotdifferfromplacebointhis studywithregardtoacutetreatment.Possibleexplana- tionsincludethattheadolescentswerenotblindto medicationassignmentinthetwoCBTcells,treatment delivereda B lowdose [ ofalargenumberofskillsand techniques,whereassomeofthemoresuccessful treatmentstudieswithCBTusedaflexibleprotocol thatfocusedmainlyoncognitiverestructuringand behavioractivation(Brent,2006;Brentetal.,1997 [rct];WeersingandWeisz,2002[ct];Woodetal.,1996 [ct]).AlthoughtheresultsoftheTreatmentof AdolescentsWithDepressionStudy(TADS)mayalso suggestthatCBTisdifficulttodisseminate,onequality improvementstudysuggestedthatCBT(sometimes deliveredincombinationwithmedication)canbe deliveredeffectivelyinprimarycaresettingsto depressedadolescentsandresultsinbetteroutcomes thantreatmentasusual(Asarnowetal.,2005[rct]). Itseemstobeclinicallyintuitiveandconsistentwith somestudiesofadultdepressivesthatthecombination ofCBTandmedicationwouldbesuperiortomedi- cationalone(Kelleretal.,2000).IntheTADS,onthe primaryoutcomes,thedifferencesbetweencombina- tionandmedicationalonewereeithernonexistentor AACAPPRACTICEPARAMETERS 1512 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. modest,althoughallpositivecontrastsdidfavorthe combination(Marchetal.,2006b;Vitielloetal., 2006).Therateofremissionwashigherincombina- tion,but,similartootherstudies,wasdisappointingly low(37%incombinationversus23%inmedication alone).ThreeotherRCTsexaminingtheeffectsof combinedtreatmentversusmedicationalonehave alsobeendisappointing.Goodyerandcolleagues (2007[rct])foundthatinmoderatelytoseverely depressedadolescentswhodidnotrespondtoabrief psychosocialtreatment,thecombinationofCBTanda selectiveserotoninreuptakeinhibitor(SSRI,mainly fluoxetine)wasnobetterthantheSSRIaloneinthe reliefofdepressivesymptomsorimprovementin overalloutcome.Melvinandcolleagues(2006[rct]) wereunabletodemonstratethesuperiorityof combinedsertralineandCBTovereithertreatment aloneforadolescentswithmildtomoderate depression.Afteracutetreatment,CBTwasfound tobesuperiortosertralinealone,whichmaysuggest anadvantageofCBT,butmayalsobeexplainedby therelativelylowsertralinedose.Finally,Clarkeand colleagues(2005[rct])comparedtheadditionof CBTtoSSRImanagementinprimarycareand foundsomemodestimprovementonqualityoflife butnotontheprimaryoutcome.Moreover,an unexpectedresultofthecombinedtreatmentwas thatthosepatientsweremorelikelytodiscontinue theirSSRIs. IPTisemergingasanotherefficaciouspsychotherapy foradolescentdepressionforwhichithasbeenshown tobesuperiortotwice-monthlysupportiveclinical management,withdifferencesmostprominentinthose whoweremoderatelyorseverelydepressedandinolder teens(Mufsonetal.,1999,2004[rct]).IPThasbeen showntobeatleastasefficaciousasCBTforadolescent depression(RosselloandBernal,1999[rct]).IPT appearstoberelativelyeasytodisseminateinsofaras therapistsinschool-basedhealthclinicswithbrief trainingandsupervisionwereabletoimprovedepres- sionusingIPTcomparedwithtreatmentasusual (Mufsonetal.,2004). Mostoftheabove-notedclinicaltrialsinclinically referredpopulationswerecarriedoutwithadolescents ratherthaninyoungerchildren,butsomerandomized CBTtrialsforsymptomaticvolunteershavebeen successfullyusedinyoungerchildren(Reynoldsand Coates,1986[rct];Starketal.,1987[rct];Weiszetal., 1997[rct]),althoughinsome,butnotall,studiesCBT wasbetterthanwaitlistcontrol,butnotanalternative treatment.Mostcliniciansrecommendtheadaptation ofcognitive,interpersonal,andpsychodynamictech- niquesforyoungerchildren.Inaddition,becauseofthe prominentroleoffamilyissuesinearly-onsetdepres- sionandthegreaterdependencyofthechildonparents, someformoffamilyinterventionisrecommended. However,noRCTshavebeenconductedinclinically referreddepressedchildren. Becausefamilyinteractionisrelatedtotheonsetand courseofadolescentdepression(Asarnowetal.,1993 [rct];Birmaheretal.,2000[ut];Nomuraetal.,2002; Pilowskyetal.,2006),theimprovementoffamily interactionsisalogicaltreatmenttargetofadolescent depression.However,onlyoneRCThasexaminedthe impactoffamilytherapyandfoundthatCBTwas superiortoasystemicbehavioralfamilytherapyinthe short-termreductionofadolescentdepression(Brent etal.,1997[rct]).Oneformoffamilytreatmenttermed attachmenttherapyhasshownpromiseasaninterven- tionandwassuperiortowaitlistcontrolforreliefof depressivesymptomatology(Diamondetal.,2002[ut]). Thereisasubstantialcase-basedliteratureonthe treatmentofdepressionwithindividualpsychodynamic psychotherapyaswellassubstantialclinicalexperience indicatingthatindividualpsychodynamicpsychother- apycanaddressabroadrangeofthecomorbidities indepressedyouthsincludingdevelopmental,inter- personal,andintrapersonalfactorsimportanttosocial, peer,andeducationalfunctioning.Inadditiontoclose monitoringofmedicationsandsymptomatology, psychodynamicinterventionscanbeusefultohelp changepatients _ depressivebeliefs,worldexpectations, andchallengenotionsoffutilityandthemeaningof life.RecentopentrialsandanRCTcomparing psychodynamicpsychotherapyplusparentsupport versusfamilytherapyforthetreatmentofyouthswith depressivedisordersarepromising,butfurtherstudies withstate-of-the-artmethodologyarenecessary(Crits- Christophetal.,2002[ut];Muratorietal.,2003[ut]; Trowelletal.,2007[rct]). Itisimportanttoemphasizethatalthoughtheabove- notedresearchstudiestrytoisolatespecificdiagnostic entitiesforclinicaltrials,mostcasesinclinicalpractice havemultiplefactorsnecessitatingamultimodaltreat- mentapproachincludingacombinationofoptionssuch asCBT,IPTinterventions,individualpsychodynamic DEPRESSIVEDISORDERS 1513 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. psychotherapy,familytherapyschool/learninginter- ventions,and/orcommunityconsultation. Pharmacotherapy. Onewaytoconceptualizethe efficacyoftreatmentistocalculatethenumberneeded totreat(NNT)togetoneresponsethatitisattributable toactivetreatmentandnotplacebo.Acrossallofthe publishedandunpublishedSSRIRCTs,depressed patientstreatedwithSSRIshavearelativelygood responserate(40% Y 70%),buttheplaceboresponse rateisalsohigh(30% Y 60%),resultinginanoverall NNTof10(95%confidenceinterval[CI]7 Y 14; Bridgeetal.,2007[rct];Cheungetal.,2005[rct]; Wagner,2005[rct]).Withtheexceptionofthe fluoxetinestudies(e.g.,Emslieetal.,1997[rct]),due tothehighplaceboresponses,significantdifferences betweenSSRIsandplacebowereonlyfoundin depressedadolescents(Bridgeetal.,2007).The differencebetweentheresponsetoSSRIsandplacebo isinverselyrelatedtothenumberofsitesinvolvedinthe study(Bridgeetal.,2007;Cheungetal.,2005). Fluoxetineistheonlymedicationtobeapprovedbythe U.S.FoodandDrugAdministration(FDA)forthe treatmentofchildandadolescentdepression,andit showsalargerdifferencebetweenmedicationand placebothandotrialswithotherantidepressants.It isnotclearwhetherthisisduetoactualdifferences intheeffectofthemedication,tootherrelated propertiesofthemedication(longhalf-lifemay lessentheimpactofpooradherencetotreatment), orthestudiesinvolvingfluoxetinewerebetter designedandconductedorusedmoreseverely depressedpatients. Severalstudiesshowedsmallornodifferences betweentheSSRIandplacebo,inpartbecausethe ratesofplaceboresponsewerehigh(e.g.,Wagneretal., 2003[rct]).Thus,itispossiblethatthedepressive symptomsinyouthsmaybehighlyresponsiveto supportivemanagement,thesestudiesincludedsubjects withmilddepressions,orothermethodologicalissues areresponsibleforthelackofdifferencebetween medicationandplacebo,suchasincludingsubjectswith mildtomoderatedepressionandlowmedicationdoses (forareviewofthelimitationsofcurrentpharmaco- logicaltrials,seeCheungetal.,2005). Therateofremission(e.g.,Children _ sDepression RatingScale-Revisedscore e 28[Poznanskiand Mokros,1995]),amorestringentandyetmore clinicallyrelevantoutcome,rangedbetween30%and 40%(Emslieetal.,1997,2002[rct];Goodyeretal., 2007[rct];Kennardetal.,2006[rct];Marchetal., 2004[rct];Wagneretal.,2003[rct]).Possible explanationsforthelowrateofremissionarethat optimalpharmacologicaltreatmentmayinvolvea higherdoseorlongerdurationoftreatment,the lackoftreatmentofcomorbidconditionsmayaffect depressivesymptoms,and/orsomechildrenand adolescentsneedtoreceiveacombinationofboth pharmacologicalandpsychosocialinterventions. Fewtrialshaveevaluatedtheeffectsofotherclassesof antidepressantsforthetreatmentofdepressedyouths. SofartheseRCTshaveshownnodifferencesbetween venlafaxineormirtazapineandplacebo(Bridgeetal., 2007;Cheungetal.,2005[rct];Emslieetal.,2007 [rct];Wagner,2005[rct]).Secondaryanalysisofthe venlafaxinetrialsshowedanageeffect,withthese medicationsbeingbetterthanplacebofordepressed adolescents,butnotdepressedchildren(Emslieetal., 2007[rct]);however,childrenweretreatedwithlow venlafaxinedoses.Onestudyshowedbetterresponsein mostmeasurementsbetweennefazodoneandplacebo foradolescentswithMDD,butasecondstudy includingdepressedchildrenandadolescentswas negative(Cheungetal.,2005).Theresponseratesfor theabove-notedantidepressantsandforplaceboare comparablewiththoseoftheSSRIs.Smallopen-label studieshavesuggestedbupropion _ seffectivenessin treatingadolescentMDDwithandwithoutADHD (e.g.,Davissetal.,2001[ct]),buttherearenoRCTs. Similarly,nocontrolledstudiesusingduloxetinehave beenreportedforthetreatmentofyouthswithMDD. Finally,RCTsaswellasameta-analysishaveshown thattricyclicantidepressantsarenomoreefficacious thanplaceboforthetreatmentofchildandadolescent depression(Hazelletal.,2006)andshouldnotbeused asafirst-linemedication.Moreover,theyareassociated withmoresideeffectsthantheSSRIsandcanbefatal afteranoverdose. SideEffects. Overall,theSSRIsandothernovel antidepressantshavebeenwelltoleratedbyboth childrenandadolescents,withfewshort-termside effects.ThesideeffectsoftheSSRIsandother serotonergicand/oradrenergicreuptakeinhibitors novelantidepressantsappeartobesimilaranddose dependentandmaysubsidewithtime(Cheungetal., 2005;Emslieetal.,2006;Findlingetal.,2002; Leonardetal.,1997;SaferandZito,2006).Themost AACAPPRACTICEPARAMETERS 1514 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. commonsideeffectsincludegastrointestinalsymptoms, sleepchanges(e.g.,insomniaorsomnolence,vivid dreams,nightmares,impairedsleep),restlessness, diaphoresis,headaches,akathisia,changesinappetite (increaseordecrease),andsexualdysfunction.Approxi- mately3%to8%ofyouths,particularlychildren,also mayshowincreasedimpulsivity,agitation,irritability, silliness,and B behavioralactivation [ (Martinetal., 2004;SaferandZito,2006;Wilensetal.,1998).These symptomsshouldbedifferentiatedfrommaniaor hypomaniathatmayappearinchildrenandadolescents with,orpredisposedtodevelop,bipolardisorder (Wilensetal.,1998).Morerarely,theuseofanti- depressantshasbeenassociatedwithserotoninsyn- drome(BoyerandShannon,2005),increased predispositiontobleeding(e.g.,easybruising,epistaxis; Lakeetal.,2000;Weinriebetal.,2005),andincreased suicidality(seebelowfordetails).Becauseoftheriskfor bleeding,patientstreatedwithSSRIsandother antidepressantswhoaregoingtohavesurgeryshould informtheirphysiciansbecausetheymaywishto discontinuetreatmentduringthepreoperativeperiod. Venlafaxineandperhapsothernoradrenergicreuptake inhibitorsmayelevatethebloodpressureandcause tachycardia.Mirtazapine,aserotoninandadrenergic receptorblocker,mayincreaseappetite,weight,and somnolence.Trazodone,aserotonin2Areceptor blockerandweakserotoninreuptakeinhibitor,and mirtazapinearemainlyusedasadjunctiveandtransient treatmentsforinsomnia.Trazodoneshouldbeused withcautioninmalesbecauseitcaninducepriapism. Nefazodone,aserotonin2Areceptorblockerandweak serotoninreuptakeinhibitor,wastakenoffthemarket amidrarereportsofhepaticfailurebeingassociated withitsuse.Althoughtherateofserioushepatic involvementisfourtimeshigherthaninSSRIs,the absoluterateisstillextremelylow.Theuseof non Y long-actingpreparationsofbupropionwasasso- ciatedwithseizures,particularlyifthedoseswerehigher than400mg/dayorwereincreasedrapidlyandpossibly ifsubjectshadbulimia.Thelong-termsideeffectsofall antidepressantshavenotbeensystematicallyevaluated inchildrenandadolescents. SuicidalIdeation/Attempts. TheFDA,incollabora- tionwithColumbiaUniversity,evaluatedtheeffectson suicidalityofnineantidepressantsusedin24acute RCTs(16MDD,4OCD,2generalizedanxiety disorder,1SAD,and1ADHD;Hammadetal.,2006; Posneretal.,2007).Theprimaryoutcomeswere spontaneouslyreportedoccurrencesofsuicidalideation andbehavior, B suicidaladverseevents, [ andusingthe suicidalitemsofdepressiveratingsscales,representing emergenceorworseningofsuicidality.Thesuicide adverseeventsanalysesshowedanoverallriskratio (RR)forsuicidalityof1.95(95%CI1.28 Y 2.98).The overallRRforsuicidalideationwas1.74(95%CI 1.06 Y 2.86)andforsuicidalattempts,itwas1.9 (1.0 Y 2.86).WhenanalyseswererestrictedtoMDD trialsforSSRIs,theoverallRRwas1.66(95%CI 1.02 Y 2.68).Amongtheantide pressants,onlythe venlafaxine(andmorerecentlyfluoxetineinthe TADS;Hammadetal.,2006)showedastatistically significantassociationwithsuicidality.Interestingly, however,themajorityofthevenlafaxinesuicidalevents involvedideationandnotbehavior.Ingeneral,these resultstranslatetoonetothreespontaneouslyreported suicideadverseeventsforevery100youthstreatedwith oneoftheantidepressantsincludedintheFDAmeta- analyses.Therewerefewsuicidalattemptsandno completions.Incontrasttotheanalysesofthesuicide adverseevents,evaluationoftheincidenceofsuicidal ideationandattemptsascertainedthroughratingscales in17studiesdidnotshowsignificantonsetor worseningofsuicidality(RRsapproximately0.90; Hammadetal.,2006). Theaboveresultsneedtobeunderstoodinthe contextofthelimitationsoftheFDAstudysuchasusing themetricofrelativerisk,whichislimitedtotrialswith atleastoneevent,inabilitytogeneralizetheresultsto populationsnotincludedinRCTs,short-termdata,not includingalloftheavailableRCTs,andmultiple comparisonsandthemethodologicallimitationsof spontaneouslygenerateddata(Hammadetal.,2006). Amorerecent,thoroughmeta-analysisextendedthe FDAanalysesbyincludingmorepublishedand unpublishedantidepressantRCTs(15MDD,6 OCD,and6anxietydisorders;Bridgeetal.,2007). Usingstatisticalmethodssimilartothoseusedbythe FDAstudy,thismeta-analysisfoundacomparable overallsmallbutsignificantincreasedrelativeriskfor spontaneousreportedsuicidality(Bridgeetal.,2007). Whenusingpooledrandomeffectsanalysesofrisk differencesinsteadofrelativerisk,boththenewanalyses oftheFDAdataandtherecentmeta-analysesyieldeda small,butsignificantoverallriskdifference(drugminus placebo;FDA:0.80,95%CI0.1 Y 1.5versusBridge DEPRESSIVEDISORDERS 1515 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. etal.:0.7,95%CI0.1 Y 1.3).However,therewereno longersignificantdifferencesforMDD(Bridgeetal., 2007).Moreover,theoverallnumberneededtoharm (NNTtoobserveoneadverseeventthatcanbe attributedtotheactivetreatment)forMDDwas112 (Bridgeetal.,2007).Asstatedabove,theoverallNNT fortheantidepressantsinpediatricdepressionis10. Thus,takingintoaccountthelimitationofanymeta- analysis,nearly11timesmoredepressedpatientsmay respondfavorablytoantidepressantsthanmaysponta- neouslyreportsuicidality. AsstatedbytheFDA(Hammadetal.,2006), theimplicationsandclinicalsignificanceregarding theabove-notedfindingsareuncertainbecausewiththe increaseinuseofSSRIs,therehasbeenadramatic declineinadolescentsuicide(Olfsonetal.,2003). Moreover,pharmacoepide miologicalstudies,while correlativeratherthancausal,supportapositive relationshipbetweenSSRIuseandthereductionin theadolescentandyoungadultsuiciderate(Gibbons etal.,2005,2006;Olfsonetal.,2003;Valucketal., 2004).Also,tworecentstudiesshowedincreasedsuicide attemptsonlyimmediatelybeforetreatmentwithSSRIs orpsychotherapy(SimonandSavarino,2007),and, similartotheTADS,improvedsuicidalideationafter treatmentwasinitiated. Howcanweunderstandthatthereareincreasedrates ofspontaneouslyreportedseriousadverseeffectson drugversusplacebo,butnotanydifferencesin suicidalityonregularlyassessedclinicalmeasures?The cluemaybeintheterm B spontaneous [ andexplana- tionsoftheassociationbetweendrugandsuicidality otherthancausality.Onesuchalternativeexplanationis subjectsonactivedrughavemoresideeffects(e.g., headache),and,asaresult,providersmayhavemore opportunity/contactwithsubjectstohearaboutsuicidal occurrencesasopposedtotheseeventsbeing B caused [ byantidepressants.Anotheralternativeexplanationis improvementfromtheantidepressantresultingina subjecttalkingaboutsuicidalthoughtsforthefirst time. Itispossiblethat,inasubgroupofpatientstreated withSSRIs,particularlythosealreadyagitatedand/or suicidal,thattreatmentcausesadisinhibitionthatleads toworseningofideationand/oragreatertendencyto makesuicidalthreats.Becausethiseventusuallyleadsto removalofthesubjectfromthestudyandachangein treatment,analysesthatlookattheslopeofsuicidal ideationwillnotfindaneffect.Inaddition,suicidality asmeasuredonratingscalesishighlycorrelatedwith theseverityofdepressionthatismorelikelytodecline ondrugthanonplacebo. Inconclusion,itappearsthatspontaneouslyreported eventsaremorecommoninSSRItreatment.Never- theless,giventhegreaternumberofpatientswho benefitfromSSRIsthanwhoexperiencetheseserious adverseeffects,thelackofanycompletedsuicides,and thedeclineinoverallsuicidalityonratingscales,the risk/benefitratioforSSRIuseinpediatricdepression appearstobefavorablewithcarefulmonitoring. Althoughtherisk/benefitratiofavorstheuseof SSRIs,furtherworkisrequired(Apteretal.,2006; Bridgeetal.,2007;Emslieetal.,2006;Marchetal., 2006a,b).Also,itremainstobeclarifiedwhether certainfactorssuchassex;subject _ shistoryof suicidality;familyhistoryofsuicidality;disorder(it appearsthattheeffectsaremoreobviousindepressed youths);severityofdepressivesymptomsatintake; doses,half-life,andtypeofantidepressants;timeduring treatment;withdrawalsideeffects(duetononcompli- anceormedicationshorthalf-life);inductionof agitation,activation,orhypomania;and/orsuscept- ibilitytosideeffects(e.g.,slowmetabolizersor variationsingeneticpolymorphisms)arerelatedto increasedriskofsuicidality(Apteretal.,2006;Brent, 2004;Bridgeetal.,2007;Hammadetal.,2006;Safer andZito,2006). ClinicalUse. Exceptforlowerinitialdosestoavoid unwantedeffects,thedosesoftheantidepressantsin childrenandadolescentsaresimilartothoseusedfor adultpatients(Findlingetal.,2002;Leonardetal., 1997).Somestudieshavereportedthatthehalf-livesof sertraline,citalopram,paroxetine,andbupropionSR aremuchshorterthanreportedinadults(Axelsonetal., 2002,Davissetal.,2005;Findlingetal.,2006). Therefore,psychiatrist sshouldbealertforthe possibilityofwithdrawalsideeffectswhenthese medicationsareprescribedoncedaily.Also,toavoid sideeffectsandimproveadherencetotreatment,itis recommendedtostartwithalowdoseandincreaseit slowlyuntilappropriatedoseshavebeenachieved. Patientsshouldbetreatedwithadequateandtolerable dosesforatleast4weeks.Clinicalresponseshouldbe assessedat4-weekintervals,andifthechildhas toleratedtheantidepressant,thedosemaybeincreased ifacompleteresponsehasnotbeenobtained AACAPPRACTICEPARAMETERS 1516 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. (Heiligensteinetal.,2006;Hughesetal.,2007).At eachstep,adequatetimeshouldbeallowedforclinical response,andfrequent,earlydoseadjustmentsshould beavoided.However,patientswhoareshowing minimalornoresponseafter8weeksoftreatment arelikelytoneedalternativetreatments.Furthermore, byabout12weeksoftreatment,thegoalshouldbe remissionofsymptoms,andinyouthswhoarenot remittedbythattime,alternativetreatmentoptions maybewarranted.Otherstrategiesfornonresponders aredescribedinRecommendation15. Giventhesmallbutstatisticallysignificantassocia- tionbetweentheantidepressantsandsuicidality,itis recommendedthatallofthepatientsreceivingthese medicationsbecarefullymonitoredforsuicidal thoughtsandbehavioraswellasothersideeffects thoughttobepossiblyassociatedwithincreased suicidality,suchasakathisia,irritability,withdrawal effects,sleepdisruption,increasedagitation,and inductionofmaniaoramixedstate,particularlyduring thefirstweeksoftreatment.TheFDArecommends thatdepressedyouthsshouldbeseeneveryweekforthe first4weeksandbiweeklythereafter,althoughitisnot alwayspossibletoscheduleweeklyface-to-faceappoint- ments.Inthiscase,evaluationsshouldbebrieflycarried outbytelephone,butitisimportanttoemphasizethat therearenodatatosuggestthatthemonitoring scheduleproposedbytheFDAortelephonecallshave anyimpactontheriskofsuicide.Monitoringis importantforallpatients,butpatientsatincreasedrisk ofsuicide(e.g.,thosewithcurrentorpriorsuicidality, impulsivity,substanceabuse,historyofsexualabuse, familyhistoryofsuicide)shouldbescrutinized particularlyclosely.Thosewithafamilyhistoryof bipolardisordershouldbecarefullymonitoredfor onsetofmaniaormixedstate.Afterthecontinuationor maintenancephasesareover,orwhentheantidepres- santsneedtobediscontinued,allantidepressants, exceptforfluoxetine,shouldbediscontinuedslowly. Fluoxetine,becauseofitslonghalf-life,istheexception andcanbestoppedatonce.Abruptdiscontinuation ofantidepressantsmayinducewithdrawalsymptoms, someofwhichmaymimicarelapseorrecurrenceof adepressiveepisode(e.g.,tiredness,irritability,severe somaticsymptoms;Zajeckaetal.,1997).Sometimes withdrawalsymptomscanbeaccompaniedbyworsen- ingoremergentsuicidalsymptoms.Thewithdrawal symptomscanappearafterassoonas6to8weekson theantidepressantsandwithin24to48hoursof discontinuation. Carefulattentiontopossiblemedicationinteractions isrecommendedbecausemostantidepressantsinhibit, tovaryingdegrees,themetabolismofseveralmedica- tionsthataremetabolizedbythediverseclustersof hepaticcytochromeP-450isoenzymes.Inaddition, interactionsofantidepressantswithotherserotonergic and/ornoradrenergicmedications,inparticular,mono- amineoxidaseinhibitors,mayinducetheserotonergic syndrome,markedbyagitation,confusion,and hyperthermia(BoyerandShannon,2005). Forfurtherinformationregardingthemanagement ofmedication,refertothePracticeParameterforthe UseofPsychotropicMedicationsinChildrenand Adolescents(AmericanAcademyofChildandAdoles- centPsychiatry,submitted). Recommendation10.ToConsolidatetheResponsetothe AcuteTreatmentandAvoidRelapses,TreatmentShould AlwaysBeContinuedfor6to12Months[MS]. Innaturalisticstudiesofdepressedpatientstreated witheitherCBTorfluoxetine,therateofrelapseishigh (Birmaheretal.,2000[ut];Emslieetal.,1998[ut]; Krolletal.,1996[ut]),withthehighestriskforrelapse within4monthsofsymptomaticimprovement.After 12weeksofopentreatmentwithfluoxetine,a6-month randomized,controlledfluoxetinediscontinuationtrial alsoshowedthatcontinuedtreatmentwiththisSSRI wasassociatedwithamuchlowerrateofrelapse(40%) comparedtotreatmentwithplacebo(69%;Emslie etal.,2004[ut]).Thehighrelapserateonfluoxetine wasaccountedfor,atleastinpart,bythepooradher- encetotreatment.Residualdepressivesymptomsafter theopentrialwereassociatedwithhigherratesof relapseduringthediscontinuationtrial,indicatingthe needtoseekremissionandnotonlyresponseto treatment.MonthlycontinuationtherapywithCBT alsoresultedinamuchlowerrelapseratethanthat foundinahistoricalcontrolgroupthatreceivedacute treatmentfollowedbynocontinuationtreatment(Kroll etal.,1996[ct]). Untilfurtherresearchbecomesavailable,continua- tiontherapyforatleast6to12monthsisrecom- mendedforallpatientswhohaverespondedtothe acutetreatment.Oftendiscontinuationcanbetried duringthesummer,sothatarelapsewouldbeless disruptivetoschoolfunction;however,itisimportantto DEPRESSIVEDISORDERS 1517 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. notethatthetreatmentfordepressioncanalsobe helpingotherdisorders(e.g.,anxiety)anddiscontinua- tionmayacceleratethesymptomsoftheseother conditions.Duringthecontinuationphase,patients typicallyareseenatleastmonthly,dependingonclinical status,functioning,supportsystems,environmental stressors,motivationfortreatment,andthepresenceof comorbidpsychiatricormedicaldisorders.Inthis phase,psychotherapyconsolidatestheskillslearned duringtheacutephaseandhelpspatientscopewiththe psychosocialsequelaeofthedepression,butalso addressestheantecedents,contextualfactors,environ- mentalstressors,andinternalaswellasexternalconflicts thatmaycontributetoarelapse.Moreover,ifthepatient istakingantidepressants,follow-upsessionsshould continuetofostermedicationadherence,optimizethe dose,andevaluateforthepresenceofsideeffects. Recommendation11.ToAvoidRecurrences,Some DepressedChildrenandAdolescentsShouldBe MaintainedinTreatmentforLongerPeriodsofTime[CG]. AsdiscussedintheClinicalCoursesection,MDD isarecurrentillness.Thus,oncethechildhasbeen asymptomaticforapproximately6to12months,the clinicianmustdecidewhethermaintenancetherapyis indicatedandthetypeanddurationoftherapy.Themain goalofthemaintenancephaseistofosterhealthygrowth anddevelopmentandpreventrecurrences.Thisphase maylast1yearorlongerandistypicallyconductedwith visitsatafrequencyofmonthlytoquarterly,depending onthepatient _ sclinicalstatus,functioning,support systems,environmentalstressors,motivationfortreat- ment,existenceofcomorbidpsychiatric/medicaldis- orders,andavailabilityandskilloftheclinician. Therearenotreatmentstudiesofyouthstoguide cliniciansastowhichpatientsrequirealongerperiod ofcontinuationandmaintenancetreatment.Inadults, thosewithatleastthreeepisodesofrecurrentdepression requirelongerperiodsoftreatment(e.g.,atleast3 Y 5 years;Kupferetal.,1992).Onegeneralruleofthumbis thatthelongerittakesforapatienttorecoverorthe higherthenumberofrecurrences,thelongertheperiod ofmaintenance.Specifically,thosepatientswithatleast twoepisodesofdepressionoronesevereepisodeor chronicepisodesofdepressionshouldhavemainte- nancetreatmentforlongerthan1year.Thosewith doubledepression(depressionwithcomorbidDD) whohavebeendepressed B aslongastheycan remember [ mayneedtreatmentindefinitely,withan explanationtofamiliesthatthereisnohard-and-fast ruleaboutthisbecauseofalackofstudiesinthis population.Moreover,otherfactorsthatarerelatedto riskofaprolongedepisodeorrecurrenceshouldalso maketheclinicianconsidermaintenancetreatments. Thesefactorsincludepatientfactorsofcomorbidity, psychosis,suicidality,numberofpriorepisodes, environmentalfactorssuchasfamilydisruptiondue toconditionsexternaltothechild(e.g.,divorce,illness, jobloss,homelessness),familypsychopathology,and lackofcommunitysupport. Finally,itisimportanttotreattheyouthsnotonly foracertainlengthoftimebutalsototreattoachieve noorminimalresidualsymptomsbecausechildren andadolescentswhohavenotrecoveredfullyandstill havesubsyndromaldepressionaremorevulnerableto recurrence(Brentetal.,2001;Lewinsohnetal.,1994; Pineetal.,1998). Recommendation12.DepressedPatientsWithPsychosis, SeasonalDepression,andBipolarDisorderMayRequire SpecificSomaticTreatments[CG]. PsychoticDepression. Althoughtherearefewstudiesin youths(Gelleretal.,1985[ct]),itappearsthatthe combinationofantidepressantswithantipsychoticsmay behelpfulforpatientswithpsychoticdepression. However,vagueormildpsychoticsymptomsina depressedchildmayrespondtoantidepressantsalone. Clinicalconsensusrecommendstheatypicalantipsy- choticmedicationscombinedwithSSRIsasthe treatmentofchoicefordepressedpsychoticyouths.It isimportanttobeawareoftheshort-andlong-termside effectsassociatedwiththeuseofatypicalantipsychotics andpossibleinteractionswiththeantidepressants.How longthesemedicationsshouldbecontinuedafterthe psychoticsymptomshaveimprovedisaquestion,butin generaltherecommendationistoslowlytaperoffthese medications,withtheeventualgoalofkeepingthechild onmonotherapywithanantidepressant. Inadultselectroconvulsivetherapyisparticularly effectiveforthissubtypeofdepression.Noncontrolled reportssuggestthatthistreatmentalsomaybeuseful fordepressedpsychoticadolescents(AmericanAcademy ofChildandAdolescentPsychiatry,2004). SAD. AsmallRCTshowedthatbrightlighttherapy isefficaciousforyouthswithSAD(Swedoetal.,1997 AACAPPRACTICEPARAMETERS 1518 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. [rct]).Itappearsthatpatientsmayrespondbetter duringthemorninghours,butmorninghoursmaybe difficultonschooldaysandforyouthswhorefuseto wakeupearlyinthemorning.Brightlighttherapyhas beenassociatedwithsomesideeffects,suchashead- achesandeyestrain.Someauthorshaverecommended anophthalmologicalevaluationbeforeinitiatinglight therapy,butthispracticehasbeenfrequentlyques- tionedunlesspatientshaveahistoryofeyeillness. Treatmentwithlightmayinduceepisodesofhypoma- niaormaniainvulnerablepatients. BipolarDisorder. Thesymptomsofunipolarand bipolardepressionaresimilar;therefore,earlyinthe courseofillness,itisdifficulttodeterminewhethera patientneedsonlyanantidepressantorwouldbenefit fromconcomitantuseofmoodstabilizers.Asnoted underDifferentialDiagnosis,somespecificsymptoms maywarntheclinicianaboutthepossibilitythatthe childisatriskofthedevelopmentofamanicor hypomanicepisode.Sometimesthechildexperiences mildrecurrenthypomanicsymptomsthatoftenare overlooked.Ifindicatorsofriskofbipolardisorderare present(seeDifferentialDiagnosissection),thenthe clinicianshoulddiscusswiththepatientandfamilythe prosandconsofinitiatingaprophylacticmood- stabilizingagent.Patientswithapsychoticdepression maybeatgreaterriskofdevelopingbipolardisorder (Gelleretal.,1994;StroberandCarlson,1982). Formildtomoderateunipolardepressioninpatients withabipolardiathesis,itmaybebesttostartwith psychotherapybecausetheriskofmanicconversion withtheuseofantidepressantsissubstantial(Martin etal.,2004).Also,ifthereisastrongsuspicionthatthe childhasbipolardisorder,amoodstabilizer,suchas lithiumcarbonate,valproate,orlamotriginemaybe indicated,particularlyifthepatientpresentswitha depressivedisordermarkedbymoodlability(for furtherdiscussionofthetreatmentofbipolardepres- sion,seeKowatchetal.,2005). Recommendation13.TreatmentShouldIncludethe ManagementofComorbidConditions[MS]. Itisofprimeimportancetotreatthecomorbid conditionsthatfrequentlyaccompanyMDDbecause theseconditionsmayinfluencetheinitiation,main- tenance,andrecurrenceofdepression;reducethe probabilityofacompletetreatmentresponse;and increasetheriskofsuicide,otherfunctionalimpairment inschool,andproblemswithinterpersonalrela- tionshipsassociatedwithMDD(Birmaheretal., 1996,2002;Curryetal.,2006;Davissetal.,2001 [ct];Fombonneetal.,2001a,b;HamiltonandBridge, 1999;Hughesetal.,1990,2007).Likewise,depressive symptomsalsomaynegativelyinfluencethetreatmentof comorbiddisorders.Althoughtherearefewstudies(e.g., Davissetal.,2001[ct])toguidetheclinicianinhowto sequencethetreatmentofdepressionandothercomorbid disorders,wesuggestthattheclinicianmakeadetermi- nationofwhichconditioniscausingthegreatestdistress andfunctionalimpairmentandbegintreatmentwiththat disorder.Also,ifrecoveryfromdepressionisunlikely untilacomorbidconditionisaddressed(e.g.,severe malnutritioninanorexia,severesubstancedependence suchascocaineorintravenousdrugdependence),then thecomorbidconditionmustbeaddressedfirst. Severalpsychosocialandpharmacologicaltreatments usedtotreatdepressionalsomaybeusefulforthe treatmentofcomorbidconditions,particularlyanxiety disorders(Bridgeetal.,2007).Fordepressedyouthswith comorbidsubstanceabuse,itisimportanttotreatboth disordersbecausedepressivesymptomatologyincreases theriskofpersistentsubstanceabuseandviceversa; abuseworsenstheprognosisofthedepression,and depressioncomorbidwithsubstanceabuseisapotentset ofriskfactorsforcompletedsuicide(AmericanAcademy ofChildandAdolescentPsychiatry,2001;Gouldetal., 1998).OneRCTinadultsaswellasanopentrialin adolescentswithdepressioncomorbidwithalcohol abusefoundthatfluoxetinewassuperiortoplaceboin reductionofbothdepressivesymptomsandalcoholuse (Corneliusetal.,2001).However,additionalstudies regardingtheuseofpsychosocialandpharmacological treatmentsfordepressedyouthswithcomorbidsub- stanceabusearenecessary. Therearefewpublishedstudiesexaminingthe efficacyofpsychopharmacologicalorpsychotherapeutic treatmentsfordepressioninmedicallyillchildrenand adolescents.Studiesarenecessary,however,because diagnosabledepressionmayoccurfrequentlyinchil- drenandadolescentswithmedicaldiseases,andmedical illnessanditstreatmentmaychangethenaturalcourse ofdepression(Lewinsohnetal.,1996).Furthermore, thepharmacokinetics,pharmacodynamics,andside effectsoftheantidepressantsmaybeaffectedbyboth themedicalillnessesandmedicationsusedtotreatthese illnesses.Psychotherapyisusefulnotonlyfortreating DEPRESSIVEDISORDERS 1519 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. depressioninthesechildrenbutalsoforhelpingthese patientsandtheirfamiliescopewiththemedicalillness (Kovacsetal.,1996;Szigethyetal.,2004[ut]). Recommendation14.DuringAllTreatmentPhases, CliniciansShouldArrangeFrequentFollow-upContacts ThatAllowSufficientTimetoMonitortheSubject _ sClinical Status,EnvironmentalConditions,and,IfAppropriate, MedicationSideEffects[MS]. Symptomsofdepression,suicidalorhomicidal ideation,maniaorhypomania;developmentofnew comorbiddisorders;psychosocialandacademicfunc- tioning;andenvironmentalconditionsshouldbe reviewedfrequentlybyinterviewingthechild,parents, and,ifappropriate,otherinformants(e.g.,teachers). Traditionally,treatmentresponsehasbeendetermined bytheabsenceofMDDcriteria(e.g.,nomorethanone DSM symptom;seeRecommendation6)or,more frequently,byasignificantreduction(e.g., Q 50%)in symptomseverity.However,usingthelattercriterion, patientsdeemed B responders [ maystillhaveconsider- ableresidualsymptoms.Therefore,anabsolutefinal scoreontheBeckDepressionInventory e 9(Beckand Steer,1987)orChildren _ sDepressionRatingScale (PoznanskiandMokros,1995) e 28togetherwith persistentimprovementinpatient _ sfunctioningforat least2weeksorlongermaybetterreflectasatisfactory response.Overallimprovementhasalsobeenmeasured usingascoreof1or2(verymuchormuchimprove- ment)intheClinicalGlobalImpressionScale,Improve- mentsubscale(Guy,1976). Becausethegoalistorestorefunctionandnotjust reducesymptoms,alackofprogressinfunctionalstatus isanimportantcluethatthedepressionisincompletely treatedorthatimpairedfunctionalstatusisduetoa comorbidpsychiatricormedicaldisorderorenviron- mentalfactors.Thefunctionalimprovementcanbe measuredusingseveralratingscalessuchasascore Q 70 ontheGlobalAssessmentofFunctioning( DSM-IV ; AmericanPsychiatricAssociation,2000b)ortheChil- dren _ sGlobalAssessmentScale(Shafferetal.,1983). Ifapatientisbeingtreatedwithmedications,thenitis importanttoevaluatetheadherencetomedicationtreat- ment,presenceofsideeffects,andyouthandparent beliefsaboutthemedicationbenefitsanditssideeffectsthat maycontributetopooradherenceorprematurediscon- tinuationoftreatment.Historyofsuicidality,homicidal ideation,andsomaticsymptomsshouldbeevaluatedbe- forestartingthepharmacologicaltreatment,andduring treatmenttheyshouldbedifferentiatedfromsymptoms ofmoodandotherpsychiatricormedicalconditions. Recommendation15.DuringAllTreatmentPhases,fora ChildorAdolescentWhoIsNotRespondingtoAppropriate Pharmacologicaland/orPsychotherapeuticTreatments, ConsiderFactorsAssociatedWithPoorResponse[MS]. Whenmanagingpatientswhoarenotrespondingto treatment,thefollowingreasonsfortreatmentfailure shouldbeconsidered:misdiagnosis,unrecognizedor untreatedcomorbidpsychiatricormedicaldisorders (e.g.,anxiety,dysthymic,eating,substanceuse,person- ality,hypothyroidism),undetectedbipolardisorder, inappropriatepharmacotherapyorpsychotherapy, inadequatelengthoftreatmentordose,lackofadherence totreatment,medicationsideeffects,exposuretochronic orseverelifeevents(e.g.,sexualabuse,ongoingfamily conflicts),personalidentityissues(e.g.,concernabout same-sexattraction),cultural/ethnicfactors,andan inadequatefitwith,orskilllevelof,thepsychotherapist. PreliminaryresultsoftheNIMHmulticenterstudy, theTreatmentofResistantDepressioninAdolescents (TORDIA),showedthatindepressedadolescentswho havefailedtorespondtoanadequatetrialwithaSSRI, aswitchtoanotherantidepressantplusCBTresultedin abetterresponsethanaswitchtoanotherantidepres- santwithoutadditionalpsychotherapy(Brentetal., 2007[rct]). OpensmallstudiesusinglithiumandMAOI augmentationhaveshowncontradictoryresults(Ryan etal.,1988a[ut],b;Stroberetal.,1992[ut]).Adult studiessuggestthataugmentationwithT3isefficacious andwell-tolerated,butsuchstudieshavenotbeen conductedinyoungerpopulations(Cooper-Kazazetal., 2007[rct]).Salleeetal.(1997[rct])foundthatintra- venousclomipraminewassuperiortoplaceboforadoles- centswithtreatment-resistantdepression.Finally,some reportshavesuggestedthatadolescentswithtreatment- resistantdepressionmayrespondtoECT(American AcademyofChildandAdolescentPsychiatry,2004), butfurtherresearchinthisareaisneeded. Severalpsychopharmacologicalstrategieshavebeen recommendedforadultswithresistantdepressionthat maybeapplicabletoyouths:optimization(extendingthe initialmedicationtrialand/oradjustingthedose,addi- tionofCBTorIPT),switchingtoanotheragentinthe sameoradifferentclassofmedications,augmentation,or AACAPPRACTICEPARAMETERS 1520 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. acombination(e.g.,lithium,T 3 ;Hughesetal.,2007). Optimizationandaugmentationstrategiesareusually usedwhenpatientshaveshownapartialresponsetothe currentregimen,andswitchingisusuallyusedwhen patientshavenotrespondedorcannottoleratethe medications,butnostudieshavevalidatedthesepractices inchildren.Inalandmarkstudyoftreatment-resistant depressedadults,afterunsuccessfultreatmentwithan SSRI,approximatelyoneinfourpatientshadaremission ofsymptomsafterswitchingtoanotherantidepressant (Rushetal.,2006[rct],Trivedietal.,2006[rct]).In addition,acombinationofmedicationplusCBThas beenshowntobesuperiortomedicationmanagement aloneforthetreatmentofpartialrespondersandforthe preventionforrelapse(Favaetal.,2004[ut];Kelleretal., 2000[rct]).Aswitchfromonemodalityoftreatmentto another(medicationtopsychotherapyorviceversa)has beenfoundtobehelpfulforsomechronicallydepressed adultswhohavefailedonemonotherapy(Schatzberg etal.,2005[ut]).Depressedadolescentsandadultswith ahistoryofsexualabusemayshowalowerlikelihood forresponsetostandardtreatmentsandmayneeda psychotherapeuticapproachthatdealswithinterpersonal issuesandtheaftereffectsofthetrauma(Barbe etal.,2004b[rct]).Also,depressedadolescentsran- domizedtoCBTandfluoxetineshowedthehighest responsewhencomparedtothosetreatedwithmono- therapywithCBT,fluoxetine,orplacebo,althoughpost hoccomparisonbetweencombinationandfluoxetine alonewasnotsignificantlydifferent,and,formoresevere depressions,thecombinationwasnotsuperiorto fluoxetinealone(Curryetal.,2006[rct]).Finally,the useofsomatictherapiesthathavenotbeenwellstudied inchildrensuchastranscranialmagneticstimulation ormoreintensivesomatictherapiesfordepressedteens suchaselectroconvulsivetherapyshouldbeconsidered. Eachoftheabove-notedstrategiesrequiresimple- mentationinasystematicfashion,educationofthe patientandfamily,andsupportandeducationto reducethepotentialforthepatienttobecomehopeless. PREVENTION Recommendation16.ChildrenWithRiskFactors AssociatedWithDevelopmentofDepressiveDisorders ShouldHaveAccesstoEarlyServicesInterventions[CG]. SeveralRCTsusingpsychoeducation,cognitive,cop- ingandsocialskills,andfamilytherapyhavetargeted childrenandadolescentsdeemedtobeatriskof depressionbyvirtueofhavingsubsyndromaldepressive symptoms,apreviousepisodeofdepression,and/ora familyhistoryofdepression(Beardsleeetal.,2003; Clarkeetal.,1995,2001,2002[rct];Jaycoxetal.,1994 [rct];Weiszetal.,1997[rct]). Arecentmeta-analysisoftheexistingliterature regardingthepreventionofdepressivesymptomsin youthshowedthatprogramsthatincludedpopulations atriskweremoreeffectivethanthosetargetinggeneral populations(universalstudies),particularlyforfemales andoldersubjects.However,theeffectsofthese treatmentsweresmalltomodest,bothimmediately post-interventionandatanaveragefollow-upof6 months(HorowitzandGarber,2006). Successfultreatmentofmotherswithdepression wasassociatedwithsignificantlyfewernewpsychia- tricdiagnosesandhigherremissionratesofexisting disordersintheirchildren(Weissmanetal.,2006a). Maternaldepressionhasalsobeenassociatedwith lessresponsetoCBTfordepression(Brentetal., 1998).Thesefindingssupporttheimportanceof earlyidentificationandvigoroustreatmentfor depressedmothersinprimarycareorpsychiatric clinics. Early-onsetdysthymiaisassociatedwithanincreased riskofMDD(Kovacsetal.,1994),indicatingtheneed forearlytreatment.Also,thereisevidencethatanxiety disorderisaprecursorofdepression(Kovacsetal., 1989;Pineetal.,1998;Weissmanetal.,2005),and treatmentofthisdisordermayreducetheonsetand recurrencesofdepression(Daddsetal.,1999;Hayward etal.,2000).BecauseSSRIsappeartohaveamuch greaterefficacyforanxietythanfordepression,vigorous detectionandtreatmentofanxietydisordersmay reducetheriskofsubsequentdepression. Thestrategiesforthepreventionofonsetorof recurrenceofdepressionshouldincludetheameliora- tionofriskfactorsassociatedwiththisdisorder.In addition,preventionmayalsoincludelifestylemodi- fications:regularandadequatesleep,exercise,acoping planforstress(e.g.,meditation,yoga,exercise,social activities),pursuitofenjoyableandmeaningfulactiv- ities,andavoidanceofsituationsthatarepredictably stressfulandnonproductive.Forthosewithrecurrent depression,aproactiveplantoavoidstressorsandaplan forcopingwithanticipateddifficultiesmaybehelpful inrelapseandrecurrenceprevention.Finally,itis DEPRESSIVEDISORDERS 1521 J.AM.ACAD.CHILDADOLESC.PSYCHIATRY,46:11,NOVEMBER2007 Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. importanttoeducatecaregivers,schoolpersonnel, pediatricians,andyouthsaboutthewarningsignsof depressivedisorderandappropriatesourcesofassess- mentandtreatment. PARAMETERLIMITATIONS AACAPpracticeparametersaredevelopedtoassist cliniciansinpsychiatricdecisionmaking.Thesepara- metersarenotintendedtodefinethestandardofcare, norshouldtheybedeemedinclusiveofalloftheproper methodsofcareorexclusiveofothermethodsofcare directedatobtainingthedesiredresults.Theultimate judgmentregardingthecareofaparticularpatient mustbemadebytheclinicianinlightofallofthe circumstancespresentedbythepatientandhisorher family,thediagnosticandtreatmentoptionsavailable, andavailableresources. Disclosure:Dr.Birmaherparticipatesorhasparticipatedinforumsfor SolvayPharmaceuticals,Inc.,andAbcomm,Inc.,andreceivesroyalties fromRandomHouse.Dr.Buksteinreceivesorhasreceivedresearch support,actedasaconsultantto,and/orservedonthespeakers _ bureaus ofCephalon,Forest,McNeilPediatrics,Shire,EliLilly,andNovartis. Drs.Brent,BernetandWalterhavenofinancialrelationshipsto disclose. 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