Major depressive disorder - Wikipedia

Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, ... Majordepressivedisorder FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Mentaldisorderinvolvingpersistentlowmood,lowself-esteem,andlossofinterest Forothertypesofdepression,seeMooddisorder. NottobeconfusedwithDepression(mood). MedicalconditionMajordepressivedisorderOthernamesClinicaldepression,majordepression,unipolardepression,unipolardisorder,recurrentdepressionSorrowingOldMan(AtEternity'sGate)byVincentvanGogh(1890)SpecialtyPsychiatry,clinicalpsychologySymptomsLowmood,lowself-esteem,lossofinterestinnormallyenjoyableactivities,lowenergy,painwithoutaclearcause[1]ComplicationsSelf-harm,suicide[2]Usualonset20s[3][4]Duration>2weeks[1]CausesEnvironmental(adverselifeexperiences,stressfullifeevents),geneticandpsychologicalfactors[5]RiskfactorsFamilyhistory,majorlifechanges,certainmedications,chronichealthproblems,substanceusedisorder[1][5]DifferentialdiagnosisBipolardisorder,ADHD,sadness[6]TreatmentPsychotherapy,antidepressantmedication,electroconvulsivetherapy,exercise[1][7]MedicationAntidepressantsFrequency163million(2017)[8] Majordepressivedisorder(MDD),alsoknownasclinicaldepression,isamentaldisorder[9]characterizedbyatleasttwoweeksofpervasivelowmood,lowself-esteem,andlossofinterestorpleasureinnormallyenjoyableactivities.Thoseaffectedmayalsooccasionallyhavedelusionsorhallucinations.[1]IntroducedbyagroupofUScliniciansinthemid-1970s,[10]thetermwasadoptedbytheAmericanPsychiatricAssociationforthissymptomclusterundermooddisordersinthe1980versionoftheDiagnosticandStatisticalManualofMentalDisorders(DSM-III),andhasbecomewidelyusedsince. Thediagnosisofmajordepressivedisorderisbasedontheperson'sreportedexperiencesandamentalstatusexamination.[11]Thereisnolaboratorytestforthedisorder,buttestingmaybedonetoruleoutphysicalconditionsthatcancausesimilarsymptoms.[11]Themostcommontimeofonsetisinaperson's20s,[3][4]withfemalesaffectedabouttwiceasoftenasmales.[4]Thecourseofthedisordervarieswidely,fromoneepisodelastingmonthstoalifelongdisorderwithrecurrentmajordepressiveepisodes. Thosewithmajordepressivedisorderaretypicallytreatedwithpsychotherapyandantidepressantmedication.[1]Medicationappearstobeeffective,buttheeffectmayonlybesignificantinthemostseverelydepressed.[12][13]Hospitalization(whichmaybeinvoluntary)maybenecessaryincaseswithassociatedself-neglectorasignificantriskofharmtoselforothers.Electroconvulsivetherapy(ECT)maybeconsideredifothermeasuresarenoteffective.[1] Majordepressivedisorderisbelievedtobecausedbyacombinationofgenetic,environmental,andpsychologicalfactors,[1]withabout40%oftheriskbeinggenetic.[5]Riskfactorsincludeafamilyhistoryofthecondition,majorlifechanges,certainmedications,chronichealthproblems,andsubstanceusedisorders.[1][5]Itcannegativelyaffectaperson'spersonallife,worklife,oreducationaswellassleeping,eatinghabits,andgeneralhealth.[1][5]Majordepressivedisorderaffectedapproximately163 millionpeople(2%oftheworld'spopulation)in2017.[8]Thepercentageofpeoplewhoareaffectedatonepointintheirlifevariesfrom7%inJapanto21%inFrance.[4]Lifetimeratesarehigherinthedevelopedworld(15%)comparedtothedevelopingworld(11%).[4]Thedisordercausesthesecond-mostyearslivedwithdisability,afterlowerbackpain.[14] Contents 1Symptomsandsigns 2Cause 2.1Genetics 2.2Otherhealthproblems 3Pathophysiology 4Diagnosis 4.1Clinicalassessment 4.2DSMandICDcriteria 4.2.1Majordepressiveepisode 4.2.2Subtypes 4.3Differentialdiagnoses 5Screeningandprevention 6Management 6.1Lifestyle 6.2Talkingtherapies 6.3Antidepressants 6.4Othermedicationsandsupplements 6.5Electroconvulsivetherapy 6.6Other 7Prognosis 7.1Abilitytowork 7.2Lifeexpectancyandtheriskofsuicide 8Epidemiology 8.1Comorbidity 9History 10Societyandculture 10.1Terminology 10.2Stigma 11Intheelderly 12Research 13References 13.1Citedworks Symptomsandsigns An1892lithographofawomandiagnosedwithmelancholia Majordepressionsignificantlyaffectsaperson'sfamilyandpersonalrelationships,workorschoollife,sleepingandeatinghabits,andgeneralhealth.[15]Apersonhavingamajordepressiveepisodeusuallyexhibitsalowmood,whichpervadesallaspectsoflife,andaninabilitytoexperiencepleasureinpreviouslyenjoyableactivities.[16]Depressedpeoplemaybepreoccupiedwith—orruminateover—thoughtsandfeelingsofworthlessness,inappropriateguiltorregret,helplessnessorhopelessness.[17]Othersymptomsofdepressionincludepoorconcentrationandmemory,withdrawalfromsocialsituationsandactivities,reducedsexdrive,irritability,andthoughtsofdeathorsuicide.Insomniaiscommon;inthetypicalpattern,apersonwakesveryearlyandcannotgetbacktosleep.Hypersomnia,oroversleeping,canalsohappen.[18]Someantidepressantsmayalsocauseinsomniaduetotheirstimulatingeffect.[19]Inseverecases,depressedpeoplemayhavepsychoticsymptoms.Thesesymptomsincludedelusionsor,lesscommonly,hallucinations,usuallyunpleasant.[20]Peoplewhohavehadpreviousepisodeswithpsychoticsymptomsaremorelikelytohavethemwithfutureepisodes.[21] Adepressedpersonmayreportmultiplephysicalsymptomssuchasfatigue,headaches,ordigestiveproblems;physicalcomplaintsarethemostcommonpresentingproblemindevelopingcountries,accordingtotheWorldHealthOrganization'scriteriafordepression.[22]Appetiteoftendecreases,resultinginweightloss,althoughincreasedappetiteandweightgainoccasionallyoccur.[23]Familyandfriendsmaynoticeagitationorlethargy.[18]Olderdepressedpeoplemayhavecognitivesymptomsofrecentonset,suchasforgetfulness,[24]andamorenoticeableslowingofmovements.[25] Depressedchildrenmayoftendisplayanirritableratherthanadepressedmood;[18]mostloseinterestinschoolandshowasteepdeclineinacademicperformance.[26]Diagnosismaybedelayedormissedwhensymptomsareinterpretedas"normalmoodiness."[23] Cause Furtherinformation:BiologyofdepressionandEpigeneticsofdepression Acupanalogydemonstratingthediathesis–stressmodelthatunderthesameamountofstressors,person2ismorevulnerablethanperson1,becauseoftheirpredisposition.[27] Thebiopsychosocialmodelproposesthatbiological,psychological,andsocialfactorsallplayaroleincausingdepression.[5][28]Thediathesis–stressmodelspecifiesthatdepressionresultswhenapreexistingvulnerability,ordiathesis,isactivatedbystressfullifeevents.Thepreexistingvulnerabilitycanbeeithergenetic,[29][30]implyinganinteractionbetweennatureandnurture,orschematic,resultingfromviewsoftheworldlearnedinchildhood.[31]AmericanpsychiatristAaronBecksuggestedthatatriadofautomaticandspontaneousnegativethoughtsabouttheself,theworldorenvironment,andthefuturemayleadtootherdepressivesignsandsymptoms.[32][33] Adversechildhoodexperiences(incorporatingchildhoodabuse,neglectandfamilydysfunction)markedlyincreasetheriskofmajordepression,especiallyifmorethanonetype.[5]Childhoodtraumaalsocorrelateswithseverityofdepression,poorresponsivenesstotreatmentandlengthofillness.Somearemoresusceptiblethanotherstodevelopingmentalillnesssuchasdepressionaftertrauma,andvariousgeneshavebeensuggestedtocontrolsusceptibility.[34] Genetics Familyandtwinstudiesfindthatnearly40%ofindividualdifferencesinriskformajordepressivedisordercanbeexplainedbygeneticfactors.[35]Likemostpsychiatricdisorders,majordepressivedisorderislikelyinfluencedbymanyindividualgeneticchanges.In2018,agenome-wideassociationstudydiscovered44geneticvariantslinkedtoriskformajordepression;[36]a2019studyfound102variantsinthegenomelinkedtodepression.[37]Researchfocusingonspecificcandidategeneshasbeencriticizedforitstendencytogeneratefalsepositivefindings.[38]Therearealsoothereffortstoexamineinteractionsbetweenlifestressandpolygenicriskfordepression.[39] Otherhealthproblems Depressioncanalsocomesecondarytoachronicorterminalmedicalcondition,suchasHIV/AIDSorasthma,andmaybelabeled"secondarydepression."[40][41]Itisunknownwhethertheunderlyingdiseasesinducedepressionthrougheffectonqualityoflife,orthroughsharedetiologies(suchasdegenerationofthebasalgangliainParkinson'sdiseaseorimmunedysregulationinasthma).[42]Depressionmayalsobeiatrogenic(theresultofhealthcare),suchasdrug-induceddepression.Therapiesassociatedwithdepressionincludeinterferons,beta-blockers,isotretinoin,contraceptives,[43]cardiacagents,anticonvulsants,antimigrainedrugs,antipsychotics,andhormonalagentssuchasgonadotropin-releasinghormoneagonist.[44]Substanceuseinearlyageisassociatedwithincreasedriskofdevelopingdepressionlaterinlife.[45]Depressionoccurringaftergivingbirthiscalledpostpartumdepressionandisthoughttobetheresultofhormonalchangesassociatedwithpregnancy.[46]Seasonalaffectivedisorder,atypeofdepressionassociatedwithseasonalchangesinsunlight,isthoughttobetriggeredbydecreasedsunlight.[47] VitaminB2,B6andB12deficiencymaycausedepressioninfemales.[48] Pathophysiology Furtherinformation:BiologyofdepressionandEpigeneticsofdepression Thepathophysiologyofdepressionisnotcompletelyunderstood,butcurrenttheoriescenteraroundmonoaminergicsystems,thecircadianrhythm,immunologicaldysfunction,HPA-axisdysfunctionandstructuralorfunctionalabnormalitiesofemotionalcircuits. Derivedfromtheeffectivenessofmonoaminergicdrugsintreatingdepression,themonoaminetheorypositsthatinsufficientactivityofmonoamineneurotransmittersistheprimarycauseofdepression.Evidenceforthemonoaminetheorycomesfrommultipleareas.First,acutedepletionoftryptophan—anecessaryprecursorofserotoninandamonoamine—cancausedepressioninthoseinremissionorrelativesofpeoplewhoaredepressed,suggestingthatdecreasedserotonergicneurotransmissionisimportantindepression.[49]Second,thecorrelationbetweendepressionriskandpolymorphismsinthe5-HTTLPRgene,whichcodesforserotoninreceptors,suggestsalink.Third,decreasedsizeofthelocuscoeruleus,decreasedactivityoftyrosinehydroxylase,increaseddensityofalpha-2adrenergicreceptor,andevidencefromratmodelssuggestdecreasedadrenergicneurotransmissionindepression.[50]Furthermore,decreasedlevelsofhomovanillicacid,alteredresponsetodextroamphetamine,responsesofdepressivesymptomstodopaminereceptoragonists,decreaseddopaminereceptorD1bindinginthestriatum,[51]andpolymorphismofdopaminereceptorgenesimplicatedopamine,anothermonoamine,indepression.[52][53]Lastly,increasedactivityofmonoamineoxidase,whichdegradesmonoamines,hasbeenassociatedwithdepression.[54]However,themonoaminetheoryisinconsistentwithobservationsthatserotonindepletiondoesnotcausedepressioninhealthypersons,thatantidepressantsinstantlyincreaselevelsofmonoaminesbuttakeweekstowork,andtheexistenceofatypicalantidepressantswhichcanbeeffectivedespitenottargetingthispathway.[55]Oneproposedexplanationforthetherapeuticlag,andfurthersupportforthedeficiencyofmonoamines,isadesensitizationofself-inhibitioninraphenucleibytheincreasedserotoninmediatedbyantidepressants.[56]However,disinhibitionofthedorsalraphehasbeenproposedtooccurasaresultofdecreasedserotonergicactivityintryptophandepletion,resultinginadepressedstatemediatedbyincreasedserotonin.Furthercounteringthemonoaminehypothesisisthefactthatratswithlesionsofthedorsalraphearenotmoredepressivethancontrols,thefindingofincreasedjugular5-HIAAinpeoplewhoaredepressedthatnormalizedwithselectiveserotoninreuptakeinhibitor(SSRI)treatment,andthepreferenceforcarbohydratesinpeoplewhoaredepressed.[57]Alreadylimited,themonoaminehypothesishasbeenfurtheroversimplifiedwhenpresentedtothegeneralpublic.[58] Immunesystemabnormalitieshavebeenobserved,includingincreasedlevelsofcytokinesinvolvedingeneratingsicknessbehavior(whichsharesoverlapwithdepression).[59][60][61]Theeffectivenessofnonsteroidalanti-inflammatorydrugs(NSAIDs)andcytokineinhibitorsintreatingdepression,[62]andnormalizationofcytokinelevelsaftersuccessfultreatmentfurthersuggestimmunesystemabnormalitiesindepression.[63] HPA-axisabnormalitieshavebeensuggestedindepressiongiventheassociationofCRHR1withdepressionandtheincreasedfrequencyofdexamethasonetestnon-suppressioninpeoplewhoaredepressed.However,thisabnormalityisnotadequateasadiagnosistool,becauseitssensitivityisonly44%.[64]Thesestress-relatedabnormalitiesarethoughttobethecauseofhippocampalvolumereductionsseeninpeoplewhoaredepressed.[65]Furthermore,ameta-analysisyieldeddecreaseddexamethasonesuppression,andincreasedresponsetopsychologicalstressors.[66]Furtherabnormalresultshavebeenobscuredwiththecortisolawakeningresponse,withincreasedresponsebeingassociatedwithdepression.[67] Theoriesunifyingneuroimagingfindingshavebeenproposed.Thefirstmodelproposedisthelimbic-corticalmodel,whichinvolveshyperactivityoftheventralparalimbicregionsandhypoactivityoffrontalregulatoryregionsinemotionalprocessing.[68]Anothermodel,thecortico-striatalmodel,suggeststhatabnormalitiesoftheprefrontalcortexinregulatingstriatalandsubcorticalstructuresresultindepression.[69]Anothermodelproposeshyperactivityofsaliencestructuresinidentifyingnegativestimuli,andhypoactivityofcorticalregulatorystructuresresultinginanegativeemotionalbiasanddepression,consistentwithemotionalbiasstudies.[70] Diagnosis Clinicalassessment Furtherinformation:Ratingscalesfordepression Caricatureofamanwithdepression Adiagnosticassessmentmaybeconductedbyasuitablytrainedgeneralpractitioner,orbyapsychiatristorpsychologist,[15]whorecordstheperson'scurrentcircumstances,biographicalhistory,currentsymptoms,familyhistory,andalcoholanddruguse.Theassessmentalsoincludesamentalstateexamination,whichisanassessmentoftheperson'scurrentmoodandthoughtcontent,inparticularthepresenceofthemesofhopelessnessorpessimism,self-harmorsuicide,andanabsenceofpositivethoughtsorplans.[15]Specialistmentalhealthservicesarerareinruralareas,andthusdiagnosisandmanagementisleftlargelytoprimary-careclinicians.[71]Thisissueisevenmoremarkedindevelopingcountries.[72]Ratingscalesarenotusedtodiagnosedepression,buttheyprovideanindicationoftheseverityofsymptomsforatimeperiod,soapersonwhoscoresaboveagivencut-offpointcanbemorethoroughlyevaluatedforadepressivedisorderdiagnosis.Severalratingscalesareusedforthispurpose;[73]theseincludetheHamiltonRatingScaleforDepression,[74]theBeckDepressionInventory[75]ortheSuicideBehaviorsQuestionnaire-Revised.[76] Primary-carephysicianshavemoredifficultywithunderrecognitionandundertreatmentofdepressioncomparedtopsychiatrists.Thesecasesmaybemissedbecauseforsomepeoplewithdepression,physicalsymptomsoftenaccompanydepression.Inaddition,theremayalsobebarriersrelatedtotheperson,provider,and/orthemedicalsystem.Non-psychiatristphysicianshavebeenshowntomissabouttwo-thirdsofcases,althoughthereissomeevidenceofimprovementinthenumberofmissedcases.[77] Beforediagnosingmajordepressivedisorder,adoctorgenerallyperformsamedicalexaminationandselectedinvestigationstoruleoutothercausesofsymptoms.TheseincludebloodtestsmeasuringTSHandthyroxinetoexcludehypothyroidism;basicelectrolytesandserumcalciumtoruleoutametabolicdisturbance;andafullbloodcountincludingESRtoruleoutasystemicinfectionorchronicdisease.[78]Adverseaffectivereactionstomedicationsoralcoholmisusemayberuledout,aswell.Testosteronelevelsmaybeevaluatedtodiagnosehypogonadism,acauseofdepressioninmen.[79]VitaminDlevelsmightbeevaluated,aslowlevelsofvitaminDhavebeenassociatedwithgreaterriskfordepression.[80]Subjectivecognitivecomplaintsappearinolderdepressedpeople,buttheycanalsobeindicativeoftheonsetofadementingdisorder,suchasAlzheimer'sdisease.[81][82]Cognitivetestingandbrainimagingcanhelpdistinguishdepressionfromdementia.[83]ACTscancanexcludebrainpathologyinthosewithpsychotic,rapid-onsetorotherwiseunusualsymptoms.[84]Nobiologicaltestsconfirmmajordepression.[85]Ingeneral,investigationsarenotrepeatedforasubsequentepisodeunlessthereisamedicalindication. DSMandICDcriteria ThemostwidelyusedcriteriafordiagnosingdepressiveconditionsarefoundintheAmericanPsychiatricAssociation'sDiagnosticandStatisticalManualofMentalDisordersandtheWorldHealthOrganization'sInternationalStatisticalClassificationofDiseasesandRelatedHealthProblems.[86]ThelattersystemistypicallyusedinEuropeancountries,whiletheformerisusedintheUSandmanyothernon-Europeannations,[87]andtheauthorsofbothhaveworkedtowardsconformingonewiththeother.[88] BothDSM-5andICD-10markouttypical(main)depressivesymptoms.[89]ICD-10definesthreetypicaldepressivesymptoms(depressedmood,anhedonia,andreducedenergy),twoofwhichshouldbepresenttodeterminethedepressivedisorderdiagnosis.[90][91]AccordingtoDSM-5,therearetwomaindepressivesymptoms:adepressedmood,andlossofinterest/pleasureinactivities(anhedonia).Thesesymptoms,aswellasfiveoutoftheninemorespecificsymptomslisted,mustfrequentlyoccurformorethantwoweeks(totheextentinwhichitimpairsfunctioning)forthediagnosis.[92] MajordepressivedisorderisclassifiedasamooddisorderinDSM-5.[93]Thediagnosishingesonthepresenceofsingleorrecurrentmajordepressiveepisodes.[94]Furtherqualifiersareusedtoclassifyboththeepisodeitselfandthecourseofthedisorder.ThecategoryUnspecifiedDepressiveDisorderisdiagnosedifthedepressiveepisode'smanifestationdoesnotmeetthecriteriaforamajordepressiveepisode.[93]TheICD-10systemdoesnotusethetermmajordepressivedisorderbutlistsverysimilarcriteriaforthediagnosisofadepressiveepisode(mild,moderateorsevere);thetermrecurrentmaybeaddediftherehavebeenmultipleepisodeswithoutmania.[86] Majordepressiveepisode Mainarticle:Majordepressiveepisode Amajordepressiveepisodeischaracterizedbythepresenceofaseverelydepressedmoodthatpersistsforatleasttwoweeks.[23]Episodesmaybeisolatedorrecurrentandarecategorizedasmild(fewsymptomsinexcessofminimumcriteria),moderate,orsevere(markedimpactonsocialoroccupationalfunctioning).Anepisodewithpsychoticfeatures—commonlyreferredtoaspsychoticdepression—isautomaticallyratedassevere.[93]Ifthepersonhashadanepisodeofmaniaormarkedlyelevatedmood,adiagnosisofbipolardisorderismadeinstead.Depressionwithoutmaniaissometimesreferredtoasunipolarbecausethemoodremainsatoneemotionalstateor"pole".[95] BereavementisnotanexclusioncriterioninDSM-5,anditisuptothecliniciantodistinguishbetweennormalreactionstoalossandMDD.Excludedarearangeofrelateddiagnoses,includingdysthymia,whichinvolvesachronicbutmildermooddisturbance;[96]recurrentbriefdepression,consistingofbrieferdepressiveepisodes;[97][98]minordepressivedisorder,wherebyonlysomesymptomsofmajordepressionarepresent;[99]andadjustmentdisorderwithdepressedmood,whichdenoteslowmoodresultingfromapsychologicalresponsetoanidentifiableeventorstressor.[100] Subtypes TheDSM-5recognizessixfurthersubtypesofMDD,calledspecifiers,inadditiontonotingthelength,severityandpresenceofpsychoticfeatures: "Melancholicdepression"ischaracterizedbyalossofpleasureinmostorallactivities,afailureofreactivitytopleasurablestimuli,aqualityofdepressedmoodmorepronouncedthanthatofgrieforloss,aworseningofsymptomsinthemorninghours,early-morningwaking,psychomotorretardation,excessiveweightloss(nottobeconfusedwithanorexianervosa),orexcessiveguilt.[101] "Atypicaldepression"ischaracterizedbymoodreactivity(paradoxicalanhedonia)andpositivity,significantweightgainorincreasedappetite(comforteating),excessivesleeporsleepiness(hypersomnia),asensationofheavinessinlimbsknownasleadenparalysis,andsignificantlong-termsocialimpairmentasaconsequenceofhypersensitivitytoperceivedinterpersonalrejection.[102] "Catatonicdepression"isarareandsevereformofmajordepressioninvolvingdisturbancesofmotorbehaviorandothersymptoms.Here,thepersonismuteandalmoststuporous,andeitherremainsimmobileorexhibitspurposelessorevenbizarremovements.Catatonicsymptomsalsooccurinschizophreniaorinmanicepisodes,ormaybecausedbyneurolepticmalignantsyndrome.[103] "Depressionwithanxiousdistress"wasaddedintotheDSM-5asameanstoemphasizethecommonco-occurrencebetweendepressionormaniaandanxiety,aswellastheriskofsuicideofdepressedindividualswithanxiety.Specifyinginsuchawaycanalsohelpwiththeprognosisofthosediagnosedwithadepressiveorbipolardisorder.[93] "Depressionwithperi-partumonset"referstotheintense,sustainedandsometimesdisablingdepressionexperiencedbywomenaftergivingbirthorwhileawomanispregnant.DSM-IV-TRusedtheclassification"postpartumdepression,"butthiswaschangedtonotexcludecasesofdepressedwomanduringpregnancy.Depressionwithperipartumonsethasanincidencerateof3–6%amongnewmothers.TheDSM-Vmandatesthattoqualifyasdepressionwithperipartumonset,onsetoccursduringpregnancyorwithinonemonthofdelivery.[104] "Seasonalaffectivedisorder"(SAD)isaformofdepressioninwhichdepressiveepisodescomeonintheautumnorwinter,andresolveinspring.Thediagnosisismadeifatleasttwoepisodeshaveoccurredincoldermonthswithnoneatothertimes,overatwo-yearperiodorlonger.[105] Differentialdiagnoses Mainarticle:Depression(differentialdiagnoses) Toconfirmmajordepressivedisorderasthemostlikelydiagnosis,otherpotentialdiagnosesmustbeconsidered,includingdysthymia,adjustmentdisorderwithdepressedmood,orbipolardisorder.Dysthymiaisachronic,mildermooddisturbanceinwhichapersonreportsalowmoodalmostdailyoveraspanofatleasttwoyears.Thesymptomsarenotassevereasthoseformajordepression,althoughpeoplewithdysthymiaarevulnerabletosecondaryepisodesofmajordepression(sometimesreferredtoasdoubledepression).[96]Adjustmentdisorderwithdepressedmoodisamooddisturbanceappearingasapsychologicalresponsetoanidentifiableeventorstressor,inwhichtheresultingemotionalorbehavioralsymptomsaresignificantbutdonotmeetthecriteriaforamajordepressiveepisode.[100]Bipolardisorder,previouslyknownasmanic–depressivedisorder,isaconditioninwhichdepressivephasesalternatewithperiodsofmaniaorhypomania.Althoughdepressioniscurrentlycategorizedasaseparatedisorder,thereisongoingdebatebecauseindividualsdiagnosedwithmajordepressionoftenexperiencesomehypomanicsymptoms,indicatingamooddisordercontinuum.[106] Otherdisordersneedtoberuledoutbeforediagnosingmajordepressivedisorder.Theyincludedepressionsduetophysicalillness,medications,andsubstanceusedisorders.Depressionduetophysicalillnessisdiagnosedasamooddisorderduetoageneralmedicalcondition.Thisconditionisdeterminedbasedonhistory,laboratoryfindings,orphysicalexamination.Whenthedepressioniscausedbyamedication,non-medicaluseofapsychoactivesubstance,orexposuretoatoxin,itisthendiagnosedasaspecificmooddisorder(previouslycalledsubstance-inducedmooddisorder).[107] Screeningandprevention Preventiveeffortsmayresultindecreasesinratesoftheconditionofbetween22and38%.[108]Since2016,theUnitedStatesPreventiveServicesTaskForce(USPSTF)hasrecommendedscreeningfordepressionamongthoseovertheage12;[109][110]thougha2005Cochranereviewfoundthattheroutineuseofscreeningquestionnaireshaslittleeffectondetectionortreatment.[111]ScreeningthegeneralpopulationisnotrecommendedbyauthoritiesintheUKorCanada.[112] Behavioralinterventions,suchasinterpersonaltherapyandcognitive-behavioraltherapy,areeffectiveatpreventingnewonsetdepression.[108][113][114]Becausesuchinterventionsappeartobemosteffectivewhendeliveredtoindividualsorsmallgroups,ithasbeensuggestedthattheymaybeabletoreachtheirlargetargetaudiencemostefficientlythroughtheInternet.[115] TheNetherlandsmentalhealthcaresystemprovidespreventiveinterventions,suchasthe"CopingwithDepression"course(CWD)forpeoplewithsub-thresholddepression.Thecourseisclaimedtobethemostsuccessfulofpsychoeducationalinterventionsforthetreatmentandpreventionofdepression(bothforitsadaptabilitytovariouspopulationsanditsresults),withariskreductionof38%inmajordepressionandanefficacyasatreatmentcomparingfavorablytootherpsychotherapies.[113][116] Management Mainarticle:Managementofdepression Thethreemostcommontreatmentsfordepressionarepsychotherapy,medication,andelectroconvulsivetherapy.Psychotherapyisthetreatmentofchoice(overmedication)forpeopleunder18.TheUKNationalInstituteforHealthandCareExcellence(NICE)2004guidelinesindicatethatantidepressantsshouldnotbeusedfortheinitialtreatmentofmilddepressionbecausetherisk-benefitratioispoor.Theguidelinesrecommendthatantidepressantstreatmentincombinationwithpsychosocialinterventionsshouldbeconsideredfor: Peoplewithahistoryofmoderateorseveredepression Thosewithmilddepressionthathasbeenpresentforalongperiod Asasecondlinetreatmentformilddepressionthatpersistsafterotherinterventions Asafirstlinetreatmentformoderateorseveredepression. Theguidelinesfurthernotethatantidepressanttreatmentshouldbecontinuedforatleastsixmonthstoreducetheriskofrelapse,andthatSSRIsarebettertoleratedthantricyclicantidepressants.[117] AmericanPsychiatricAssociationtreatmentguidelinesrecommendthatinitialtreatmentshouldbeindividuallytailoredbasedonfactorsincludingseverityofsymptoms,co-existingdisorders,priortreatmentexperience,andpersonalpreference.Optionsmayincludepharmacotherapy,psychotherapy,exercise,electroconvulsivetherapy(ECT),transcranialmagneticstimulation(TMS)orlighttherapy.Antidepressantmedicationisrecommendedasaninitialtreatmentchoiceinpeoplewithmild,moderate,orseveremajordepression,andshouldbegiventoallpeoplewithseveredepressionunlessECTisplanned.[118]Thereisevidencethatcollaborativecarebyateamofhealthcarepractitionersproducesbetterresultsthanroutinesingle-practitionercare.[119] Treatmentoptionsaremuchmorelimitedindevelopingcountries,whereaccesstomentalhealthstaff,medication,andpsychotherapyisoftendifficult.Developmentofmentalhealthservicesisminimalinmanycountries;depressionisviewedasaphenomenonofthedevelopedworlddespiteevidencetothecontrary,andnotasaninherentlylife-threateningcondition.[120]Thereisinsufficientevidencetodeterminetheeffectivenessofpsychologicalversusmedicaltherapyinchildren.[121] Lifestyle Furtherinformation:Neurobiologicaleffectsofphysicalexercise§ Majordepressivedisorder Physicalexerciseisonerecommendedwaytomanagemilddepression. Physicalexercisehasbeenfoundtobeeffectiveformajordepression,andmayberecommendedtopeoplewhoarewilling,motivated,andhealthyenoughtoparticipateinanexerciseprogramastreatment.[122]Itisequivalenttotheuseofmedicationsorpsychologicaltherapiesinmostpeople.[7]Inolderpeopleitdoesappeartodecreasedepression.[123]Sleepanddietmayalsoplayaroleindepression,andinterventionsintheseareasmaybeaneffectiveadd-ontoconventionalmethods.[124]Inobservationalstudies,smokingcessationhasbenefitsindepressionaslargeasorlargerthanthoseofmedications.[125] Talkingtherapies Seealso:Behavioraltheoriesofdepression Talkingtherapy(psychotherapy)canbedeliveredtoindividuals,groups,orfamiliesbymentalhealthprofessionals,includingpsychotherapists,psychiatrists,psychologists,clinicalsocialworkers,counselors,andpsychiatricnurses.A2012reviewfoundpsychotherapytobebetterthannotreatmentbutnotothertreatments.[126]Withmorecomplexandchronicformsofdepression,acombinationofmedicationandpsychotherapymaybeused.[127][128]Thereismoderate-qualityevidencethatpsychologicaltherapiesareausefuladditiontostandardantidepressanttreatmentoftreatment-resistantdepressionintheshortterm.[129]Psychotherapyhasbeenshowntobeeffectiveinolderpeople.[130][131]Successfulpsychotherapyappearstoreducetherecurrenceofdepressionevenafterithasbeenstoppedorreplacedbyoccasionalboostersessions. Themost-studiedformofpsychotherapyfordepressionisCBT,whichteachesclientstochallengeself-defeating,butenduringwaysofthinking(cognitions)andchangecounter-productivebehaviors.CBTcanperformaswellasantidepressantsinpeoplewithmajordepression.[132]CBThasthemostresearchevidenceforthetreatmentofdepressioninchildrenandadolescents,andCBTandinterpersonalpsychotherapy(IPT)arepreferredtherapiesforadolescentdepression.[133]Inpeopleunder18,accordingtotheNationalInstituteforHealthandClinicalExcellence,medicationshouldbeofferedonlyinconjunctionwithapsychologicaltherapy,suchasCBT,interpersonaltherapy,orfamilytherapy.[134]Severalvariablespredictsuccessforcognitivebehavioraltherapyinadolescents:higherlevelsofrationalthoughts,lesshopelessness,fewernegativethoughts,andfewercognitivedistortions.[135]CBTisparticularlybeneficialinpreventingrelapse.[136][137]Cognitivebehavioraltherapyandoccupationalprograms(includingmodificationofworkactivitiesandassistance)havebeenshowntobeeffectiveinreducingsickdaystakenbyworkerswithdepression.[138]Severalvariantsofcognitivebehaviortherapyhavebeenusedinthosewithdepression,themostnotablebeingrationalemotivebehaviortherapy,[139]andmindfulness-basedcognitivetherapy.[140]Mindfulness-basedstressreductionprogramsmayreducedepressionsymptoms.[141][142]Mindfulnessprogramsalsoappeartobeapromisinginterventioninyouth.[143] Psychoanalysisisaschoolofthought,foundedbySigmundFreud,whichemphasizestheresolutionofunconsciousmentalconflicts.[144]Psychoanalytictechniquesareusedbysomepractitionerstotreatclientspresentingwithmajordepression.[145]Amorewidelypracticedtherapy,calledpsychodynamicpsychotherapy,isinthetraditionofpsychoanalysisbutlessintensive,meetingonceortwiceaweek.Italsotendstofocusmoreontheperson'simmediateproblems,andhasanadditionalsocialandinterpersonalfocus.[146]Inameta-analysisofthreecontrolledtrialsofShortPsychodynamicSupportivePsychotherapy,thismodificationwasfoundtobeaseffectiveasmedicationformildtomoderatedepression.[147] Antidepressants Sertraline(Zoloft)isusedprimarilytotreatmajordepressioninadults. Conflictingresultshavearisenfromstudiesthatlookattheeffectivenessofantidepressantsinpeoplewithacute,mildtomoderatedepression.[148]AreviewcommissionedbytheNationalInstituteforHealthandCareExcellence(UK)concludedthatthereisstrongevidencethatSSRIs,suchasescitalopram,paroxetine,andsertraline,havegreaterefficacythanplaceboonachievinga50%reductionindepressionscoresinmoderateandseveremajordepression,andthatthereissomeevidenceforasimilareffectinmilddepression.[149]Similarly,aCochranesystematicreviewofclinicaltrialsofthegenerictricyclicantidepressantamitriptylineconcludedthatthereisstrongevidencethatitsefficacyissuperiortoplacebo.[150] In2014theUSFoodandDrugAdministrationpublishedasystematicreviewofallantidepressantmaintenancetrialssubmittedtotheagencybetween1985and2012.Theauthorsconcludedthatmaintenancetreatmentreducedtheriskofrelapseby52%comparedtoplacebo,andthatthiseffectwasprimarilyduetorecurrentdepressionintheplacebogroupratherthanadrugwithdrawaleffect.[12] Tofindthemosteffectiveantidepressantmedicationwithminimalside-effects,thedosagescanbeadjusted,andifnecessary,combinationsofdifferentclassesofantidepressantscanbetried.Responseratestothefirstantidepressantadministeredrangefrom50to75%,anditcantakeatleastsixtoeightweeksfromthestartofmedicationtoimprovement.[118][151]Antidepressantmedicationtreatmentisusuallycontinuedfor16to20weeksafterremission,tominimizethechanceofrecurrence,[118]andevenuptooneyearofcontinuationisrecommended.[152]Peoplewithchronicdepressionmayneedtotakemedicationindefinitelytoavoidrelapse.[15] SSRIsaretheprimarymedicationsprescribed,owingtotheirrelativelymildside-effects,andbecausetheyarelesstoxicinoverdosethanotherantidepressants.[153]PeoplewhodonotrespondtooneSSRIcanbeswitchedtoanotherantidepressant,andthisresultsinimprovementinalmost50%ofcases.[154]Anotheroptionistoswitchtotheatypicalantidepressantbupropion.[155]Venlafaxine,anantidepressantwithadifferentmechanismofaction,maybemodestlymoreeffectivethanSSRIs.[156]However,venlafaxineisnotrecommendedintheUKasafirst-linetreatmentbecauseofevidencesuggestingitsrisksmayoutweighbenefits,[157]anditisspecificallydiscouragedinchildrenandadolescents.[158][159] Forchildren,someresearchhassupportedtheuseoftheSSRIantidepressantfluoxetine.[160]Thebenefithoweverappearstobeslightinchildren,[160][161]whileotherantidepressantshavenotbeenshowntobeeffective.[160]Medicationsarenotrecommendedinchildrenwithmilddisease.[162]Thereisalsoinsufficientevidencetodetermineeffectivenessinthosewithdepressioncomplicatedbydementia.[163]Anyantidepressantcancauselowbloodsodiumlevels;[164]nevertheless,ithasbeenreportedmoreoftenwithSSRIs.[153]ItisnotuncommonforSSRIstocauseorworseninsomnia;thesedatingatypicalantidepressantmirtazapinecanbeusedinsuchcases.[165][166] Irreversiblemonoamineoxidaseinhibitors,anolderclassofantidepressants,havebeenplaguedbypotentiallylife-threateningdietaryanddruginteractions.Theyarestillusedonlyrarely,althoughnewerandbetter-toleratedagentsofthisclasshavebeendeveloped.[167]Thesafetyprofileisdifferentwithreversiblemonoamineoxidaseinhibitors,suchasmoclobemide,wheretheriskofseriousdietaryinteractionsisnegligibleanddietaryrestrictionsarelessstrict.[168] Itisunclearwhetherantidepressantsaffectaperson'sriskofsuicide.[169]Forchildren,adolescents,andprobablyyoungadultsbetween18and24yearsold,thereisahigherriskofbothsuicidalideationsandsuicidalbehaviorinthosetreatedwithSSRIs.[170][171]Foradults,itisunclearwhetherSSRIsaffecttheriskofsuicidality.Onereviewfoundnoconnection;[172]anotheranincreasedrisk;[173]andathirdnoriskinthose25–65yearsoldandadecreasedriskinthosemorethan65.[174]AblackboxwarningwasintroducedintheUnitedStatesin2007onSSRIsandotherantidepressantmedicationsduetotheincreasedriskofsuicideinpeopleyoungerthan24yearsold.[175]SimilarprecautionarynoticerevisionswereimplementedbytheJapaneseMinistryofHealth.[176] Othermedicationsandsupplements Thecombineduseofantidepressantsplusbenzodiazepinesdemonstratesimprovedeffectivenesswhencomparedtoantidepressantsalone,buttheseeffectsmaynotendure.[177]Theadditionofabenzodiazepineisbalancedagainstpossibleharmsandotheralternativetreatmentstrategieswhenantidepressantmono-therapyisconsideredinadequate.[177] Thereisinsufficienthighqualityevidencetosuggestomega-3fattyacidsareeffectiveindepression.[178]ThereislimitedevidencethatvitaminDsupplementationisofvalueinalleviatingthesymptomsofdepressioninindividualswhoarevitaminD-deficient.[80]ThereissomepreliminaryevidencethatCOX-2inhibitors,suchascelecoxib,haveabeneficialeffectonmajordepression.[179]Lithiumappearseffectiveatloweringtheriskofsuicideinthosewithbipolardisorderandunipolardepressiontonearlythesamelevelsasthegeneralpopulation.[180]Thereisanarrowrangeofeffectiveandsafedosagesoflithiumthusclosemonitoringmaybeneeded.[181]Low-dosethyroidhormonemaybeaddedtoexistingantidepressantstotreatpersistentdepressionsymptomsinpeoplewhohavetriedmultiplecoursesofmedication.[182]Limitedevidencesuggestsstimulants,suchasamphetamineandmodafinil,maybeeffectiveintheshortterm,orasadjuvanttherapy.[183][184]Also,itissuggestedthatfolatesupplementsmayhavearoleindepressionmanagement.[185]Thereistentativeevidenceforbenefitfromtestosteroneinmales.[186] Electroconvulsivetherapy Electroconvulsivetherapy(ECT)isastandardpsychiatrictreatmentinwhichseizuresareelectricallyinducedinapersonwithdepressiontoproviderelieffrompsychiatricillnesses.[187]: 1880 ECTisusedwithinformedconsent[188]asalastlineofinterventionformajordepressivedisorder.[189]AroundofECTiseffectiveforabout50%ofpeoplewithtreatment-resistantmajordepressivedisorder,whetheritisunipolarorbipolar.[190]Follow-uptreatmentisstillpoorlystudied,butabouthalfofpeoplewhorespondrelapsewithintwelvemonths.[191]Asidefromeffectsinthebrain,thegeneralphysicalrisksofECTaresimilartothoseofbriefgeneralanesthesia.[192]: 259 Immediatelyfollowingtreatment,themostcommonadverseeffectsareconfusionandmemoryloss.[189][193]ECTisconsideredoneoftheleastharmfultreatmentoptionsavailableforseverelydepressedpregnantwomen.[194] AusualcourseofECTinvolvesmultipleadministrations,typicallygiventwoorthreetimesperweek,untilthepersonnolongerhassymptoms.ECTisadministeredunderanesthesiawithamusclerelaxant.[195]Electroconvulsivetherapycandifferinitsapplicationinthreeways:electrodeplacement,frequencyoftreatments,andtheelectricalwaveformofthestimulus.Thesethreeformsofapplicationhavesignificantdifferencesinbothadversesideeffectsandsymptomremission.Aftertreatment,drugtherapyisusuallycontinued,andsomepeoplereceivemaintenanceECT.[189] ECTappearstoworkintheshorttermviaananticonvulsanteffectmostlyinthefrontallobes,andlongertermvianeurotrophiceffectsprimarilyinthemedialtemporallobe.[196] Other Transcranialmagneticstimulation(TMS)ordeeptranscranialmagneticstimulationisanoninvasivemethodusedtostimulatesmallregionsofthebrain.[197]TMSwasapprovedbytheFDAfortreatment-resistantmajordepressivedisorder(trMDD)in2008[198]andasof2014evidencesupportsthatitisprobablyeffective.[199]TheAmericanPsychiatricAssociation[200]theCanadianNetworkforMoodandAnxietyDisorders,[201]andtheRoyalAustraliaandNewZealandCollegeofPsychiatristshaveendorsedTMSfortrMDD.[202] Transcranialdirectcurrentstimulation(tDCS)isanothernoninvasivemethodusedtostimulatesmallregionsofthebrainwithaweakelectriccurrent.Severalmeta-analyseshaveconcludedthatactivetDCSwasusefulfortreatingdepression.[203][204] Brightlighttherapyreducesdepressionsymptomseverity,withbenefitforbothseasonalaffectivedisorderandfornonseasonaldepression,andaneffectsimilartothoseforconventionalantidepressants.Fornonseasonaldepression,addinglighttherapytothestandardantidepressanttreatmentwasnoteffective.[205]Fornonseasonaldepression,wherelightwasusedmostlyincombinationwithantidepressantsorwaketherapy,amoderateeffectwasfound,withresponsebetterthancontroltreatmentinhigh-qualitystudies,instudiesthatappliedmorninglighttreatment,andwithpeoplewhorespondtototalorpartialsleepdeprivation.[206]Bothanalysesnotedpoorquality,shortduration,andsmallsizeofmostofthereviewedstudies. Thereisasmallamountofevidencethatsleepdeprivationmayimprovedepressivesymptomsinsomeindividuals,[207]withtheeffectsusuallyshowingupwithinaday.Thiseffectisusuallytemporary.Besidessleepiness,thismethodcancauseasideeffectofmaniaorhypomania.[208] ThereisinsufficientevidenceforReiki[209]anddancemovementtherapyindepression.[210] Asof2019[update]cannabisisspecificallynotrecommendedasatreatment.[211] Prognosis Studieshaveshownthat80%ofthosewithafirstmajordepressiveepisodewillhaveatleastonemoredepressionduringtheirlife,[212]withalifetimeaverageoffourepisodes.[213]Othergeneralpopulationstudiesindicatethataroundhalfthosewhohaveanepisoderecover(whethertreatedornot)andremainwell,whiletheotherhalfwillhaveatleastonemore,andaround15%ofthoseexperiencechronicrecurrence.[214]Studiesrecruitingfromselectiveinpatientsourcessuggestlowerrecoveryandhigherchronicity,whilestudiesofmostlyoutpatientsshowthatnearlyallrecover,withamedianepisodedurationof11months.Around90%ofthosewithsevereorpsychoticdepression,mostofwhomalsomeetcriteriaforothermentaldisorders,experiencerecurrence.[215][216]Caseswhenoutcomeispoorareassociatedwithinappropriatetreatment,severeinitialsymptomsincludingpsychosis,earlyageofonset,previousepisodes,incompleterecoveryafteroneyearoftreatment,pre-existingseverementalormedicaldisorder,andfamilydysfunction.[217] Ahighproportionofpeoplewhoexperiencefullsymptomaticremissionstillhaveatleastonenotfullyresolvedsymptomaftertreatment.[218]Recurrenceorchronicityismorelikelyifsymptomshavenotfullyresolvedwithtreatment.[218]Currentguidelinesrecommendcontinuingantidepressantsforfourtosix monthsafterremissiontopreventrelapse.Evidencefrommanyrandomizedcontrolledtrialsindicatescontinuingantidepressantmedicationsafterrecoverycanreducethechanceofrelapseby70%(41%onplacebovs.18%onantidepressant).Thepreventiveeffectprobablylastsforatleastthefirst36 monthsofuse.[219] Majordepressiveepisodesoftenresolveovertimewhetherornottheyaretreated.Outpatientsonawaitinglistshowa10–15%reductioninsymptomswithinafewmonths,withapproximately20%nolongermeetingthefullcriteriaforadepressivedisorder.[220]Themediandurationofanepisodehasbeenestimatedtobe23weeks,withthehighestrateofrecoveryinthefirstthreemonths.[221]Accordingtoa2013review,23%ofuntreatedadultswithmildtomoderatedepressionwillremitwithin3months,32%within6monthsand53%within12months.[222] Abilitytowork Depressionmayaffectpeople'sabilitytowork.Thecombinationofusualclinicalcareandsupportwithreturntowork(likeworkinglesshoursorchangingtasks)probablyreducessickleaveby15%,andleadstofewerdepressivesymptomsandimprovedworkcapacity,reducingsickleavebyanannualaverageof25daysperyear.[138]Helpingdepressedpeoplereturntoworkwithoutaconnectiontoclinicalcarehasnotbeenshowntohaveaneffectonsickleavedays.Additionalpsychologicalinterventions(suchasonlinecognitivebehavioraltherapy)leadtofewersickdayscomparedtostandardmanagementonly.Streamliningcareoraddingspecificprovidersfordepressioncaremayhelptoreducesickleave.[138] Lifeexpectancyandtheriskofsuicide Depressedindividualshaveashorterlifeexpectancythanthosewithoutdepression,inpartbecausepeoplewhoaredepressedareatriskofdyingofsuicide.[223]Upto60%ofpeoplewhodieofsuicidehaveamooddisordersuchasmajordepression,andtheriskisespeciallyhighifapersonhasamarkedsenseofhopelessnessorhasbothdepressionandborderlinepersonalitydisorder.[224]About2–8%ofadultswithmajordepressiondiebysuicide,[2][225]andabout50%ofpeoplewhodiebysuicidehaddepressionoranothermooddisorder.[226]ThelifetimeriskofsuicideassociatedwithadiagnosisofmajordepressionintheUSisestimatedat3.4%,whichaveragestwohighlydisparatefiguresofalmost7%formenand1%forwomen[227](althoughsuicideattemptsaremorefrequentinwomen).[228]Theestimateissubstantiallylowerthanapreviouslyacceptedfigureof15%,whichhadbeenderivedfromolderstudiesofpeoplewhowerehospitalized.[229] Depressedpeoplehaveahigherrateofdyingfromothercauses.[230]Thereisa1.5-to2-foldincreasedriskofcardiovasculardisease,independentofotherknownriskfactors,andisitselflinkeddirectlyorindirectlytoriskfactorssuchassmokingandobesity.Peoplewithmajordepressionarelesslikelytofollowmedicalrecommendationsfortreatingandpreventingcardiovasculardisorders,furtherincreasingtheirriskofmedicalcomplications.[231]Cardiologistsmaynotrecognizeunderlyingdepressionthatcomplicatesacardiovascularproblemundertheircare.[232] Epidemiology Mainarticle:Epidemiologyofdepression Disability-adjustedlifeyearforunipolardepressivedisordersper100,000inhabitantsin2004.[233]  nodata  <700  700–775  775–850  850–925  925–1000  1000–1075  1075–1150  1150–1225  1225–1300  1300–1375  1375–1450  >1450 Majordepressivedisorderaffectedapproximately163 millionpeoplein2017(2%oftheglobalpopulation).[8]Thepercentageofpeoplewhoareaffectedatonepointintheirlifevariesfrom7%inJapanto21%inFrance.[4]Inmostcountriesthenumberofpeoplewhohavedepressionduringtheirlivesfallswithinan8–18%range.[4]InNorthAmerica,theprobabilityofhavingamajordepressiveepisodewithinayear-longperiodis3–5%formalesand8–10%forfemales.[234][235]Majordepressionisabouttwiceascommoninwomenasinmen,althoughitisunclearwhythisisso,andwhetherfactorsunaccountedforarecontributingtothis.[236]Therelativeincreaseinoccurrenceisrelatedtopubertaldevelopmentratherthanchronologicalage,reachesadultratiosbetweentheagesof15and18,andappearsassociatedwithpsychosocialmorethanhormonalfactors.[236]Asof2017[update],depressionisthethirdmostcommonworldwidecauseofdisabilityamongbothsexes,followinglowbackpainandheadache.[237] Peoplearemostlikelytodeveloptheirfirstdepressiveepisodebetweentheagesof30and40,andthereisasecond,smallerpeakofincidencebetweenages50and60.[238]Theriskofmajordepressionisincreasedwithneurologicalconditionssuchasstroke,Parkinson'sdisease,ormultiplesclerosis,andduringthefirstyearafterchildbirth.[239]Itisalsomorecommonaftercardiovascularillnesses,andisrelatedmoretothosewithapoorcardiacdiseaseoutcomethantoabetterone.[240][241]Depressivedisordersaremorecommoninurbanpopulationsthaninruralonesandtheprevalenceisincreasedingroupswithpoorersocioeconomicfactors,e.g.,homelessness.[242] MajordepressioniscurrentlytheleadingcauseofdiseaseburdeninNorthAmericaandotherhigh-incomecountries,andthefourth-leadingcauseworldwide.Intheyear2030,itispredictedtobethesecond-leadingcauseofdiseaseburdenworldwideafterHIV,accordingtotheWHO.[243]Delayorfailureinseekingtreatmentafterrelapseandthefailureofhealthprofessionalstoprovidetreatmentaretwobarrierstoreducingdisability.[244] Comorbidity Majordepressionfrequentlyco-occurswithotherpsychiatricproblems.The1990–92NationalComorbiditySurvey(US)reportsthathalfofthosewithmajordepressionalsohavelifetimeanxietyanditsassociateddisorders,suchasgeneralizedanxietydisorder.[245]Anxietysymptomscanhaveamajorimpactonthecourseofadepressiveillness,withdelayedrecovery,increasedriskofrelapse,greaterdisabilityandincreasedsuicidalbehavior.[246]Depressedpeoplehaveincreasedratesofalcoholandsubstanceuse,particularlydependence,[247][248]andaroundathirdofindividualsdiagnosedwithattentiondeficithyperactivitydisorder(ADHD)developcomorbiddepression.[249]Post-traumaticstressdisorderanddepressionoftenco-occur.[15]DepressionmayalsocoexistwithADHD,complicatingthediagnosisandtreatmentofboth.[250]Depressionisalsofrequentlycomorbidwithalcoholusedisorderandpersonalitydisorders.[251]Depressioncanalsobeexacerbatedduringparticularmonths(usuallywinter)inthosewithseasonalaffectivedisorder.Whileoveruseofdigitalmediahasbeenassociatedwithdepressivesymptoms,usingdigitalmediamayalsoimprovemoodinsomesituations.[252][253] Depressionandpainoftenco-occur.Oneormorepainsymptomsarepresentin65%ofpeoplewhohavedepression,andanywherefrom5to85%ofpeoplewhoareexperiencingpainwillalsohavedepression,dependingonthesetting—alowerprevalenceingeneralpractice,andhigherinspecialtyclinics.Depressionisoftenunderrecognized,andthereforeundertreated,inpatientspresentingwithpain.[254]Depressionoftencoexistswithphysicaldisorderscommonamongtheelderly,suchasstroke,othercardiovasculardiseases,Parkinson'sdisease,andchronicobstructivepulmonarydisease.[255] History Mainarticle:Historyofdepression TheAncientGreekphysicianHippocratesdescribedasyndromeofmelancholiaasadistinctdiseasewithparticularmentalandphysicalsymptoms;hecharacterizedall"fearsanddespondencies,iftheylastalongtime"asbeingsymptomaticoftheailment.[256]Itwasasimilarbutfarbroaderconceptthantoday'sdepression;prominencewasgiventoaclusteringofthesymptomsofsadness,dejection,anddespondency,andoftenfear,anger,delusionsandobsessionswereincluded.[257] DiagnosesofdepressiongobackatleastasfarasHippocrates. ThetermdepressionitselfwasderivedfromtheLatinverbdeprimere,"topressdown".[258]Fromthe14thcentury,"todepress"meanttosubjugateortobringdowninspirits.Itwasusedin1665inEnglishauthorRichardBaker'sChronicletorefertosomeonehaving"agreatdepressionofspirit",andbyEnglishauthorSamuelJohnsoninasimilarsensein1753.[259]Thetermalsocameintouseinphysiologyandeconomics.AnearlyusagereferringtoapsychiatricsymptomwasbyFrenchpsychiatristLouisDelasiauvein1856,andbythe1860sitwasappearinginmedicaldictionariestorefertoaphysiologicalandmetaphoricalloweringofemotionalfunction.[260]SinceAristotle,melancholiahadbeenassociatedwithmenoflearningandintellectualbrilliance,ahazardofcontemplationandcreativity.Thenewerconceptabandonedtheseassociationsandthroughthe19thcentury,becamemoreassociatedwithwomen.[257] Althoughmelancholiaremainedthedominantdiagnosticterm,depressiongainedincreasingcurrencyinmedicaltreatisesandwasasynonymbytheendofthecentury;GermanpsychiatristEmilKraepelinmayhavebeenthefirsttouseitastheoverarchingterm,referringtodifferentkindsofmelancholiaasdepressivestates.[261]Freudlikenedthestateofmelancholiatomourninginhis1917paperMourningandMelancholia.Hetheorizedthatobjectiveloss,suchasthelossofavaluedrelationshipthroughdeathoraromanticbreak-up,resultsinsubjectivelossaswell;thedepressedindividualhasidentifiedwiththeobjectofaffectionthroughanunconscious,narcissisticprocesscalledthelibidinalcathexisoftheego.Suchlossresultsinseveremelancholicsymptomsmoreprofoundthanmourning;notonlyistheoutsideworldviewednegativelybuttheegoitselfiscompromised.[262]Theperson'sdeclineofself-perceptionisrevealedinhisbeliefofhisownblame,inferiority,andunworthiness.[263]Healsoemphasizedearlylifeexperiencesasapredisposingfactor.[257]AdolfMeyerputforwardamixedsocialandbiologicalframeworkemphasizingreactionsinthecontextofanindividual'slife,andarguedthatthetermdepressionshouldbeusedinsteadofmelancholia.[264]ThefirstversionoftheDSM(DSM-I,1952)containeddepressivereactionandtheDSM-II(1968)depressiveneurosis,definedasanexcessivereactiontointernalconflictoranidentifiableevent,andalsoincludedadepressivetypeofmanic-depressivepsychosiswithinMajoraffectivedisorders.[265] Inthemid-20thcentury,researcherstheorizedthatdepressionwascausedbyachemicalimbalanceinneurotransmittersinthebrain,atheorybasedonobservationsmadeinthe1950softheeffectsofreserpineandisoniazidinalteringmonoamineneurotransmitterlevelsandaffectingdepressivesymptoms.[266]Thechemicalimbalancetheoryhasneverbeenproven.[267] Thetermunipolar(alongwiththerelatedtermbipolar)wascoinedbytheneurologistandpsychiatristKarlKleist,andsubsequentlyusedbyhisdisciplesEddaNeeleandKarlLeonhard.[268] ThetermMajordepressivedisorderwasintroducedbyagroupofUScliniciansinthemid-1970saspartofproposalsfordiagnosticcriteriabasedonpatternsofsymptoms(calledthe"ResearchDiagnosticCriteria",buildingonearlierFeighnerCriteria),[10]andwasincorporatedintotheDSM-IIIin1980.[269]TheAmericanPsychiatricAssociationadded"majordepressivedisorder"totheDiagnosticandStatisticalManualofMentalDisorders(DSM-III),[270]asasplitofthepreviousdepressiveneurosisintheDSM-II,whichalsoencompassedtheconditionsnowknownasdysthymiaandadjustmentdisorderwithdepressedmood.[270]TomaintainconsistencytheICD-10usedthesamecriteria,withonlyminoralterations,butusingtheDSMdiagnosticthresholdtomarkamilddepressiveepisode,addinghigherthresholdcategoriesformoderateandsevereepisodes.[89][269]Theancientideaofmelancholiastillsurvivesinthenotionofamelancholicsubtype. Thenewdefinitionsofdepressionwerewidelyaccepted,albeitwithsomeconflictingfindingsandviews.Therehavebeensomecontinuedempiricallybasedargumentsforareturntothediagnosisofmelancholia.[271][272]Therehasbeensomecriticismoftheexpansionofcoverageofthediagnosis,relatedtothedevelopmentandpromotionofantidepressantsandthebiologicalmodelsincethelate1950s.[273] Societyandculture Terminology The16thAmericanpresident,AbrahamLincoln,had"melancholy",aconditionthatnowmaybereferredtoasclinicaldepression.[274] Theterm"depression"isusedinanumberofdifferentways.Itisoftenusedtomeanthissyndromebutmayrefertoothermooddisordersorsimplytoalowmood.People'sconceptualizationsofdepressionvarywidely,bothwithinandamongcultures."Becauseofthelackofscientificcertainty,"onecommentatorhasobserved,"thedebateoverdepressionturnsonquestionsoflanguage.Whatwecallit—'disease,''disorder,''stateofmind'—affectshowweview,diagnose,andtreatit."[275]Thereareculturaldifferencesintheextenttowhichseriousdepressionisconsideredanillnessrequiringpersonalprofessionaltreatment,oranindicatorofsomethingelse,suchastheneedtoaddresssocialormoralproblems,theresultofbiologicalimbalances,orareflectionofindividualdifferencesintheunderstandingofdistressthatmayreinforcefeelingsofpowerlessness,andemotionalstruggle.[276][277] Thediagnosisislesscommoninsomecountries,suchasChina.IthasbeenarguedthattheChinesetraditionallydenyorsomatizeemotionaldepression(althoughsincetheearly1980s,theChinesedenialofdepressionmayhavemodified).[278]Alternatively,itmaybethatWesternculturesreframeandelevatesomeexpressionsofhumandistresstodisorderstatus.AustralianprofessorGordonParkerandothershavearguedthattheWesternconceptofdepressionmedicalizessadnessormisery.[279][280]Similarly,Hungarian-AmericanpsychiatristThomasSzaszandothersarguethatdepressionisametaphoricalillnessthatisinappropriatelyregardedasanactualdisease.[281]TherehasalsobeenconcernthattheDSM,aswellasthefieldofdescriptivepsychiatrythatemploysit,tendstoreifyabstractphenomenasuchasdepression,whichmayinfactbesocialconstructs.[282]AmericanarchetypalpsychologistJamesHillmanwritesthatdepressioncanbehealthyforthesoul,insofaras"itbringsrefuge,limitation,focus,gravity,weight,andhumblepowerlessness."[283]HillmanarguesthattherapeuticattemptstoeliminatedepressionechotheChristianthemeofresurrection,buthavetheunfortunateeffectofdemonizingasoulfulstateofbeing. Stigma Historicalfigureswereoftenreluctanttodiscussorseektreatmentfordepressionduetosocialstigmaaboutthecondition,orduetoignoranceofdiagnosisortreatments.Nevertheless,analysisorinterpretationofletters,journals,artwork,writings,orstatementsoffamilyandfriendsofsomehistoricalpersonalitieshasledtothepresumptionthattheymayhavehadsomeformofdepression.PeoplewhomayhavehaddepressionincludeEnglishauthorMaryShelley,[284]American-BritishwriterHenryJames,[285]andAmericanpresidentAbrahamLincoln.[286]Somewell-knowncontemporarypeoplewithpossibledepressionincludeCanadiansongwriterLeonardCohen[287]andAmericanplaywrightandnovelistTennesseeWilliams.[288]Somepioneeringpsychologists,suchasAmericansWilliamJames[289][290]andJohnB.Watson,[291]dealtwiththeirowndepression. Therehasbeenacontinuingdiscussionofwhetherneurologicaldisordersandmooddisordersmaybelinkedtocreativity,adiscussionthatgoesbacktoAristoteliantimes.[292][293]Britishliteraturegivesmanyexamplesofreflectionsondepression.[294]EnglishphilosopherJohnStuartMillexperiencedaseveral-months-longperiodofwhathecalled"adullstateofnerves",whenoneis"unsusceptibletoenjoymentorpleasurableexcitement;oneofthosemoodswhenwhatispleasureatothertimes,becomesinsipidorindifferent".HequotedEnglishpoetSamuelTaylorColeridge's"Dejection"asaperfectdescriptionofhiscase:"Agriefwithoutapang,void,darkanddrear,/Adrowsy,stifled,unimpassionedgrief,/Whichfindsnonaturaloutletorrelief/Inword,orsigh,ortear."[295][296]EnglishwriterSamuelJohnsonusedtheterm"theblackdog"inthe1780stodescribehisowndepression,[297]anditwassubsequentlypopularizedbyBritishPrimeMinisterSirWinstonChurchill,whoalsohadthedisorder.[297]JohannWolfgangvonGoetheinhisFaust,PartI,publishedin1808,hasMephistophelesassumetheformofablackdog,specificallyapoodle. Socialstigmaofmajordepressioniswidespread,andcontactwithmentalhealthservicesreducesthisonlyslightly.Publicopinionsontreatmentdiffermarkedlytothoseofhealthprofessionals;alternativetreatmentsareheldtobemorehelpfulthanpharmacologicalones,whichareviewedpoorly.[298]IntheUK,theRoyalCollegeofPsychiatristsandtheRoyalCollegeofGeneralPractitionersconductedajointFive-yearDefeatDepressioncampaigntoeducateandreducestigmafrom1992to1996;[299]aMORIstudyconductedafterwardsshowedasmallpositivechangeinpublicattitudestodepressionandtreatment.[300] Intheelderly Seealso:Latelifedepression Depressionisespeciallycommonamongthoseover65yearsofageandincreasesinfrequencybeyondthisage.[301]Theriskofdepressionincreasesinrelationtothefrailtyoftheindividual.[302]Depressionisoneofthemostimportantfactorswhichnegativelyimpactqualityoflifeinadults,aswellastheelderly.[301]Bothsymptomsandtreatmentamongtheelderlydifferfromthoseoftherestofthepopulation.[301] Theelderlyindividualmaynotpresentwithclassicaldepressivesymptoms.[301]Diagnosisandtreatmentisfurthercomplicatedinthattheelderlyareoftensimultaneouslytreatedwithanumberofotherdrugs,andoftenhaveotherconcurrentdiseases.[301]Antidepressantsworklesswellfortheelderlythanforyoungerindividualswithdepression.[303] Problemsolvingtherapy,cognitivebehavioraltherapy,andinterpersonaltherapyareeffectiveinterventions.[303]ECThasbeenusedintheelderly,andregister-studiessuggestitiseffective,althoughlesssoascomparedtotherestofthepopulation.Therisksinvolvedwithtreatmentofdepressionamongtheelderlyasopposedtobenefitsarenotentirelyclear.[301]Physicalexercisemaybeparticularlyhelpfulamongtheelderlywithdepression.[304] Research Trialsareinvestigatingwhetherbotulinumtoxin,whenusedtomakeapersonappeartofrownless,stopsnegativefeedbackfromthefaceandaffectsdepression.[305] Psilocybinmayhaveabeneficialroleinthetreatmentofdepression.[306][307] 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Listentothisarticle(1hourand20minutes) Thisaudiofilewascreatedfromarevisionofthisarticledated6 October 2014 (2014-10-06),anddoesnotreflectsubsequentedits.(Audiohelp ·Morespokenarticles) ClassificationDICD-11:6A71ICD-10:F32,F33ICD-9-CM:296.2,296.3OMIM:608516MeSH:D003865DiseasesDB:3589ExternalresourcesMedlinePlus:003213eMedicine:med/532PatientUK:Majordepressivedisorder vteMentaldisorders (Classification)AdultpersonalityandbehaviorSexual Ego-dystonicsexualorientation Paraphilia Fetishism Voyeurism Sexualmaturationdisorder Sexualrelationshipdisorder Other Factitiousdisorder Munchausensyndrome Genderdysphoria Intermittentexplosivedisorder Dermatillomania Kleptomania Pyromania Trichotillomania Personalitydisorder ChildhoodandlearningEmotionalandbehavioral ADHD Conductdisorder ODD Emotionalandbehavioraldisorders Separationanxietydisorder Movementdisorders Stereotypic Socialfunctioning DAD RAD Selectivemutism Speech Cluttering Stuttering Ticdisorder Tourettesyndrome Intellectualdisability X-linkedintellectualdisability Lujan–Frynssyndrome Psychologicaldevelopment(developmentaldisabilities) Pervasive Specific Mood(affective) Bipolar BipolarI BipolarII BipolarNOS Cyclothymia Depression Atypicaldepression Dysthymia Majordepressivedisorder Melancholicdepression Seasonalaffectivedisorder Mania NeurologicalandsymptomaticAutismspectrum Autism Aspergersyndrome High-functioningautism PDD-NOS Savantsyndrome Dementia AIDSdementiacomplex Alzheimer'sdisease Creutzfeldt–Jakobdisease Frontotemporaldementia Huntington'sdisease Mildcognitiveimpairment Parkinson'sdisease Pick'sdisease Sundowning Vasculardementia Wandering Other Delirium Organicbrainsyndrome Post-concussionsyndrome Neurotic,stress-relatedandsomatoformAdjustment Adjustmentdisorderwithdepressedmood AnxietyPhobia Agoraphobia Socialanxiety Socialphobia Anthropophobia Specificsocialphobia Specificphobia Claustrophobia Other Generalizedanxietydisorder OCD Panicattack Panicdisorder Stress Acutestressdisorder PTSD Dissociative Depersonalization-derealizationdisorder Dissociativeidentitydisorder Fuguestate Psychogenicamnesia Somaticsymptom Bodydysmorphicdisorder Conversiondisorder Gansersyndrome Globuspharyngis Psychogenicnon-epilepticseizures Falsepregnancy Hypochondriasis Masspsychogenicillness Nosophobia Psychogenicpain Somatizationdisorder PhysiologicalandphysicalbehaviorEating Anorexianervosa Bulimianervosa Ruminationsyndrome Otherspecifiedfeedingoreatingdisorder Nonorganicsleep Hypersomnia Insomnia Parasomnia Nightterror Nightmare REMsleepbehaviordisorder Postnatal Postpartumdepression Postpartumpsychosis SexualdysfunctionArousal Erectiledysfunction Femalesexualarousaldisorder Desire Hypersexuality Hypoactivesexualdesiredisorder Orgasm Anorgasmia Delayedejaculation Prematureejaculation Sexualanhedonia Pain Nonorganicdyspareunia Nonorganicvaginismus Psychoactivesubstances,substanceabuseandsubstance-related Drugoverdose Intoxication Physicaldependence Reboundeffect Stimulantpsychosis Substancedependence Withdrawal Schizophrenia,schizotypalanddelusionalDelusional Delusionaldisorder Folieàdeux Psychosisandschizophrenia-like Briefreactivepsychosis Schizoaffectivedisorder Schizophreniformdisorder Schizophrenia Childhoodschizophrenia Disorganized(hebephrenic)schizophrenia Paranoidschizophrenia Pseudoneuroticschizophrenia Simple-typeschizophrenia Other Catatonia Symptomsanduncategorized Impulse-controldisorder Klüver–Bucysyndrome Psychomotoragitation Stereotypy vteMooddisorderSpectrumBipolardisorder BipolarI BipolarII Cyclothymia BipolarNOS Childhood Hypomania Mania Mixedaffectivestate Rapidcycling Depression Majordepressivedisorder Dysthymia Seasonalaffectivedisorder Atypicaldepression Melancholicdepression Majordepressiveepisode Comorbidities Schizoaffectivedisorder Symptoms Delusion Depression(differentialdiagnoses) Emotionaldysregulation Anhedonia Dysphoria Suicidalideation Hallucination Moodswing Sleepdisorder Hypersomnia Insomnia Psychosis Psychoticdepression Racingthoughts Reducedaffectdisplay Diagnosis BipolarSpectrumDiagnosticScale ChildManiaRatingScale GeneralBehaviorInventory HypomaniaChecklist MoodDisorderQuestionnaire Ratingscalesfordepression YoungManiaRatingScale TreatmentAnticonvulsants Carbamazepine Lamotrigine Oxcarbazepine Valproate Sodiumvalproate Valproatesemisodium Sympathomimetics,SSRIsandsimilar Bupropion Dextroamphetamine Escitalopram Fluoxetine Methylphenidate Sertraline Othermoodstabilizers Antipsychotics Atypicalantipsychotics Lithium Lithiumcarbonate Lithiumcitrate Lithiumsulfate Lithiumtoxicity Non-pharmaceutical Clinicalpsychology Cognitivebehavioraltherapy Dialecticalbehaviortherapy Electroconvulsivetherapy Involuntarycommitment Lighttherapy Psychotherapy Transcranialmagneticstimulation History EmilKraepelin FrederickK.Goodwin JohnCade KarlLeonhard KayRedfieldJamison MogensSchou Authoritycontrol:Nationallibraries Spain France(data) Israel UnitedStates Japan Croatia 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