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SelectiveserotoninreuptakeinhibitorWikipedia

Selectiveserotoninreuptakeinhibitor
FromWikipedia,thefreeencyclopedia

Selectiveserotoninreuptakeinhibitorsorserotoninspecificreuptakeinhibitors[1](SSRIs)areaclassofdrugsthatare
typicallyusedasantidepressantsinthetreatmentofmajordepressivedisorderandanxietydisorders.

Selectiveserotoninreuptake
inhibitor

TheexactmechanismofSSRIsisunknown.[2]SSRIsarebelievedtoincreasetheextracellularleveloftheneurotransmitter
serotoninbylimitingitsreabsorptionintothepresynapticcell,increasingthelevelofserotonininthesynapticcleftavailableto
bindtothepostsynapticreceptor.Theyhavevaryingdegreesofselectivityfortheothermonoaminetransporters,withpure
SSRIshavingonlyweakaffinityforthenorepinephrineanddopaminetransporters.

Drugclass

SSRIsarethemostwidelyprescribedantidepressantsinmanycountries.[3]TheefficacyofSSRIsinmildormoderatecasesof
depressionhasbeendisputed.[4][5][6]

Contents
1 Medicaluses
1.1 Depression
1.2 Generalizedanxietydisorder
1.3 Obsessivecompulsivedisorder
1.4 Eatingdisorders
1.5 Strokerecovery
1.6 Prematureejaculation
2 Adverseeffects
2.1 Sexualdysfunction
2.2 Cardiac
2.3 Bleeding
2.4 Discontinuationsyndrome
2.5 Suiciderisk
2.6 Pregnancyandbreastfeeding
2.7 Neonatalabstinencesyndrome
2.8 Overdose
3 Contraindicationsanddruginteractions
4 Listofagents
4.1 Relatedagents
5 Mechanismofaction
5.1 Pharmacogenetics
5.2 SSRIsversusTCAs
6 Societyandculture
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Serotonin
Classidentifiers
Use

majordepressivedisorder,anxiety
disorders

ATCcode N06AB
Biological Serotonintransporter
target
Clinicaldata
Drugs.com DrugClasses(https://www.drugs.com/d
rugclass/ssriantidepressants.html)
Consumer BestBuyDrugs
Reports
Externallinks
MeSH

D017367

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6.1 Controversy
7 Seealso
8 References
9 Externallinks

Medicaluses
ThemainindicationforSSRIsismajordepressivedisorder(alsocalled"majordepression","clinicaldepression"andoftensimply"depression").SSRIsarefrequentlyprescribed
foranxietydisorders,suchassocialanxietydisorder,panicdisorders,obsessivecompulsivedisorder(OCD),eatingdisorders,chronicpainandoccasionally,forposttraumatic
stressdisorder(PTSD).Theyarealsofrequentlyusedtotreatdepersonalizationdisorder,althoughgenerallywithpoorresults.[7]

Depression
AntidepressantsarerecommendedbytheNationalInstituteforHealthandCareExcellence(NICE)asafirstlinetreatmentofseveredepressionandforthetreatmentofmildto
moderatedepressionthatpersistsafterconservativemeasuressuchascognitivetherapy.[8]Theyrecommendagainsttheirroutineuseinthosewhohavechronichealthproblems
andmilddepression.[8]
Therehasbeencontroversyregardingtheefficacyofantidepressantsintreatingdepressiondependingonitsseverityandduration.
Twometaanalysespublishedin2008(Kirsch)and2010(Fournier)foundthatinmildandmoderatedepression,theeffectofSSRIsissmallornonecomparedtoplacebo,
whileinveryseveredepressiontheeffectofSSRIsisbetween"relativelysmall"and"substantial".[4][9]The2008metaanalysiscombined35clinicaltrialssubmittedtothe
FoodandDrugAdministration(FDA)beforelicensingoffournewerantidepressants(includingtheSSRIsparoxetineandfluoxetine,thenonSSRIantidepressant
nefazodone,andtheserotoninandnorepinephrinereuptakeinhibitor(SNRI)venlafaxine).Theauthorsattributedtherelationshipbetweenseverityandefficacytoa
reductionoftheplaceboeffectinseverelydepressedpatients,ratherthananincreaseintheeffectofthemedication.[9]Someresearchershavequestionedthestatisticalbasis
ofthisstudysuggestingthatitunderestimatestheeffectsizeofantidepressants.[10][11]
A2010comprehensivereviewconductedbyNICEconcludedthatantidepressantshavenoadvantageoverplacebointhetreatmentofshorttermmilddepression,butthat
theavailableevidencesupportedtheuseofantidepressantsinthetreatmentofdysthymiaandotherformsofchronicmilddepression.[12]
A2012metaanalysisoffluoxetineandvenlafaxineconcludedthatstatisticallyandclinicallysignificanttreatmenteffectswereobservedforeachdrugrelativetoplacebo
irrespectiveofbaselinedepressionseverity.[13]
In2014theU.S.FDApublishedasystematicreviewofallantidepressantmaintenancetrialssubmittedtotheagencybetween1985and2012.Theauthorsconcludedthat
maintenancetreatmentreducedtheriskofrelapseby52%comparedtoplacebo,andthatthiseffectwasprimarilyduetorecurrentdepressionintheplacebogrouprather
thanadrugwithdrawaleffect.[14]
Theredoesnotappeartobeabigdifferenceintheeffectivenessbetweenmedicationsinthesecondgenerationantidepressants(SSRIsandSNRIs).[15]
Inchildrenthereareconcernsaroundthequalityoftheevidenceonthemeaningfulnessofbenefitsseen.[16]Ifamedicationisused,fluoxetineappearstobefirstline.[16]

Generalizedanxietydisorder
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SSRIsarerecommendedbytheNationalInstituteforHealthandCareExcellence(NICE)forthetreatmentofgeneralizedanxietydisorder(GAD)thathasfailedtorespondto
conservativemeasuressuchaseducationandselfhelpactivities.GADisacommondisorderofwhichthecentralfeatureisexcessiveworryaboutanumberofdifferentevents.
Keysymptomsincludeexcessiveanxietyaboutmultipleeventsandissues,anddifficultycontrollingworrisomethoughtsthatpersistsforatleast6months.
AntidepressantsprovideamodesttomoderatereductioninanxietyinGAD,[17]andaresuperiortoplacebointreatingGAD.[18]Theefficacyofdifferentantidepressantsis
similar.[17][18]

Obsessivecompulsivedisorder
SSRIsareasecondlinetreatmentofadultobsessivecompulsivedisorder(OCD)withmildfunctionalimpairmentandasfirstlinetreatmentforthosewithmoderateorsevere
impairment.Inchildren,SSRIscanbeconsideredasecondlinetherapyinthosewithmoderatetosevereimpairment,withclosemonitoringforpsychiatricadverseeffects.[19]
SSRIsareefficaciousinthetreatmentofOCDpatientstreatedwithSSRIsareabouttwiceaslikelytorespondtotreatmentasthosetreatedwithplacebo.[20][21]Efficacyhasbeen
demonstratedbothinshorttermtreatmenttrialsof6to24weeksandindiscontinuationtrialsof28to52weeksduration.[22][23][24]

Eatingdisorders
Antidepressantsarerecommendedasanalternativeoradditionalfirststeptoselfhelpprogramsinthetreatmentofbulimianervosa.[25]SSRIs(fluoxetineinparticular)are
preferredoverotherantidepressantsduetotheiracceptability,tolerability,andsuperiorreductionofsymptomsinshorttermtrials.Longtermefficacyremainspoorly
characterized.
Similarrecommendationsapplytobingeeatingdisorder.[25]SSRIsprovideshorttermreductionsinbingeeatingbehavior,buthavenotbeenassociatedwithsignificantweight
loss.[26]
ClinicaltrialshavegeneratedmostlynegativeresultsfortheuseofSSRIsinthetreatmentofanorexianervosa.[27]TreatmentguidelinesfromtheNationalInstituteofHealthand
ClinicalExcellence[25]recommendagainsttheuseofSSRIsinthisdisorder.ThosefromtheAmericanPsychiatricAssociationnotethatSSRIsconfernoadvantageregarding
weightgain,butthattheymaybeusedforthetreatmentofcoexistingdepressive,anxiety,orobsessivecompulsivedisorders.[26]

Strokerecovery
SSRIshavebeenusedinthetreatmentofstrokepatients,includingthosewithandwithoutsymptomsofdepression.Arecentmetaanalysisofrandomized,controlledclinical
trialsfoundastatisticallysignificanteffectofSSRIsondependence,neurologicaldeficit,depression,andanxiety.Therewasnostatisticallysignificanteffectondeath,motor
deficits,orcognition.[28]

Prematureejaculation
SSRIsareeffectiveforthetreatmentofprematureejaculation.Chronicadministrationismoreefficaciousthanondemanduse.[29]

Adverseeffects
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Sideeffectsvaryamongtheindividualdrugsofthisclass.However,certaintypesofadverseeffectsarefoundbroadlyamongmostifnotallmembersofthisclass:
increasedriskofbonefracturesby1.7fold[30]
akathisia[31][32][33][34]
suicidalideation(thoughtsofsuicide)(seebelow)
photosensitivity[35]

Sexualdysfunction
SSRIscancausevarioustypesofsexualdysfunctionsuchasanorgasmia,erectiledysfunction,diminishedlibido,genitalnumbness,andsexualanhedonia(pleasureless
orgasm).[36]SexualproblemsarecommonwithSSRIs.[37]Poorsexualfunctionisalsooneofthemostcommonreasonspeoplestopthemedication.[38]
OccasionallysymptomsofsexualdysfunctionmaypersistafterdiscontinuationofSSRIs.[36][39][40][41]
ThemechanismbywhichSSRIscausesexualsideeffectsisnotwellunderstoodasof2015.Therangeofpossiblemechanismsincludes(1)nonspecificneurologicaleffects(e.g.,
sedation)thatgloballyimpairbehaviorincludingsexualfunction(2)specificeffectsonbrainsystemsmediatingsexualfunction(3)specificeffectsonperipheraltissuesand
organs,suchasthepenis,thatmediatesexualfunctionand(4)directorindirecteffectsonhormonesmediatingsexualfunction.[42]Itisprobablethatantidepressantsimpact
severalofthesephysiologicsubstratesofsexualfunction.Animalresearchanddatafromstudiesinhumansubjectssuggestthatsexualbehaviorandfunctionareenhancedby
increasesinbraindopaminergicfunctionandinhibitedbyincreasesinbrainserotonergicfunction.Thelatterobservationisconsistentwiththeassociationofserotonergic
antidepressants(whichincreaseserotonergictransmission)withsexualdysfunction.[43]
Anumberof(nonSSRI)drugsarenotassociatedwithsexualsideeffects(suchasbupropion,mirtazapine,tianeptine,agomelatineandmoclobemide.[44][45])
ThereisnoFDAapprovedtreatmentforSSRIinducedsexualdysfunctionandtherehasbeenalackofrandomized,placebocontrolled,doubleblindstudiesofpotential
treatments.Thereisevidenceforthefollowingmanagementstrategies:forerectiledysfunction,theadditionofaPDE5inhibitorsuchassildenafilfordecreasedlibido,possibly
addingorswitchingtobupropionandforoverallsexualdysfunction,switchingtonefazodone.[46]
SeveralsmallstudieshavesuggestedthatSSRIsmayadverselyaffectsemenquality.[47]

Cardiac
SSRIsdonotappeartoaffecttheriskofcoronaryheartdisease(CHD)inthosewithoutapreviousdiagnosisofCHD.[48]Alargecohortstudysuggestednosubstantialincreasein
theriskofcardiacmalformationsattributabletoSSRIusageduringthefirsttrimesterofpregnancy.[49]Anumberoflargestudiesofpeoplewithoutknownpreexistingheart
diseasehavereportednoEKGchangesrelatedtoSSRIuse.[50]TherecommendedmaximumdailydoseofcitalopramandescitalopramwasreducedduetoconcernswithQT
intervalprolongation.[51][52][53]Inoverdose,fluoxetinehasbeenreportedtocausesinustachycardia,myocardialinfarction,junctionalrhythmsandtrigeminy.Someauthorshave
suggestedelectrocardiographicmonitoringinpatientswithseverepreexistingcardiovasculardiseasewhoaretakingSSRIs.[54]

Bleeding
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SSRIsinteractwithanticoagulants,likewarfarinandaspirin.[55][56][57][58]ThisincludesanincreasedriskofGIbleeding,andpostoperativebleeding.[55]Therelativeriskof
intracranialbleedingisincreased,buttheabsoluteriskisverylow.[59]SSRIsareknowntocauseplateletdysfunction.[60][61]Thisriskisgreaterinthosewhoarealsoon
anticoagulants,antiplateletagentsandNSAIDs(nonsteroidalantiinflammatorydrugs),aswellaswiththecoexistenceofunderlyingdiseasessuchascirrhosisoftheliveror
liverfailure.[62][63]

Discontinuationsyndrome
Serotoninreuptakeinhibitorsshouldnotbeabruptlydiscontinuedafterextendedtherapy,andwheneverpossible,shouldbetaperedoverseveralweekstominimize
discontinuationrelatedsymptomswhichmayincludenausea,headache,dizziness,chills,bodyaches,paresthesias,insomnia,andelectricshocklikesensations.Paroxetinemay
producediscontinuationrelatedsymptomsatagreaterratethanotherSSRIs,thoughqualitativelysimilareffectshavebeenreportedforallSSRIs.[64][65]Discontinuationeffects
appeartobelessforfluoxetine,perhapsowingtoitslonghalflifeandthenaturaltaperingeffectassociatedwithitsslowclearancefromthebody.Onestrategyforminimizing
SSRIdiscontinuationsymptomsistoswitchthepatienttofluoxetineandthentaperanddiscontinuethefluoxetine.[64]

Suiciderisk
Childrenandadolescents
MetaanalysesofshortdurationrandomizedclinicaltrialshavefoundthatSSRIuseisrelatedtoahigherriskofsuicidalbehaviorinchildrenandadolescents.[66][67][68]For
instance,a2004U.S.FoodandDrugAdministration(FDA)analysisofclinicaltrialsonchildrenwithmajordepressivedisorderfoundstatisticallysignificantincreasesofthe
risksof"possiblesuicidalideationandsuicidalbehavior"byabout80%,andofagitationandhostilitybyabout130%.[69]AccordingtotheFDA,theheightenedriskofsuicidality
iswithinthefirstonetotwomonthsoftreatment.[70][71][72]TheNationalInstituteforHealthandCareExcellence(NICE)placestheexcessriskinthe"earlystagesof
treatment".[73]TheEuropeanPsychiatricAssociationplacestheexcessriskinthefirsttwoweeksoftreatmentand,basedonacombinationofepidemiological,prospectivecohort,
medicalclaims,andrandomizedclinicaltrialdata,concludesthataprotectiveeffectdominatesafterthisearlyperiod.A2012Cochranereviewfoundthatatsixtoninemonths,
suicidalideationremainedhigherinchildrentreatedwithantidepressantscomparedtothosetreatedwithpsychologicaltherapy.[74]
Arecentcomparisonofaggressionandhostilityoccurringduringtreatmentwithfluoxetinetoplaceboinchildrenandadolescentsfoundthatnosignificantdifferencebetweenthe
fluoxetinegroupandaplacebogroup.[75]ThereisalsoevidencethathigherratesofSSRIprescriptionsareassociatedwithlowerratesofsuicideinchildren,thoughsincethe
evidenceiscorrelational,thetruenatureoftherelationshipisunclear.[76]
In2004,theMedicinesandHealthcareproductsRegulatoryAgency(MHRA)intheUnitedKingdomjudgedfluoxetine(Prozac)tobetheonlyantidepressantthatoffereda
favorableriskbenefitratioinchildrenwithdepression,thoughitwasalsoassociatedwithaslightincreaseintheriskofselfharmandsuicidalideation.[77]OnlytwoSSRIsare
licensedforusewithchildrenintheUK,sertraline(Zoloft)andfluvoxamine(Luvox),andonlyforthetreatmentofobsessivecompulsivedisorder.Fluoxetineisnotlicensedfor
thisuse.[78]
Adults
ItisunclearwhetherornotSSRIsaffecttheriskofsuicidalbehaviorforadults.
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A2005metaanalysisofdrugcompanydatafoundnoevidencethatSSRIsincreasedtheriskofsuicidehowever,importantprotectiveorhazardouseffectscouldnotbe
excluded.[79]
A2005reviewobservedthatsuicideattemptsareincreasedinthosewhouseSSRIsascomparedtoplaceboandcomparedtotherapeuticinterventionsotherthantricyclic
antidepressants.NodifferenceriskofsuicideattemptswasdetectedbetweenSSRIsversustricyclicantidepressants.[80]
Ontheotherhand,a2006reviewsuggeststhatthewidespreaduseofantidepressantsinthenew"SSRIera"appearstohaveledtoahighlysignificantdeclineinsuicide
ratesinmostcountrieswithtraditionallyhighbaselinesuiciderates.Thedeclineisparticularlystrikingforwomenwho,comparedwithmen,seekmorehelpfordepression.
RecentclinicaldataonlargesamplesintheUStoohaverevealedaprotectiveeffectofantidepressantagainstsuicide.[81]
A2006metaanalysisofrandomcontrolledtrialssuggeststhatSSRIsincreasesuicideideationcomparedwithplacebo.However,theobservationalstudiessuggestthat
SSRIsdidnotincreasesuicideriskmorethanolderantidepressants.TheresearchersstatedthatifSSRIsincreasesuicideriskinsomepatients,thenumberofadditional
deathsisverysmallbecauseecologicalstudieshavegenerallyfoundthatsuicidemortalityhasdeclined(oratleastnotincreased)asSSRIusehasincreased.[82]
AnadditionalmetaanalysisbytheFDAin2006foundanagerelatedeffectofSSRI's.Amongadultsyoungerthan25years,resultsindicatedthattherewasahigherrisk
forsuicidalbehavior.Foradultsbetween25and64,theeffectappearsneutralonsuicidalbehaviorbutpossiblyprotectiveforsuicidalbehaviorforadultsbetweentheages
of25and64.Foradultsolderthan64,SSRI'sseemtoreducetheriskofbothsuicidalbehavior.[66]

Pregnancyandbreastfeeding
SSRIuseinpregnancyhasbeenassociatedwithavarietyofriskswithvaryingdegreesofproofofcausation.Asdepressionisindependentlyassociatedwithnegativepregnancy
outcomes,determiningtheextenttowhichobservedassociationsbetweenantidepressantuseandspecificadverseoutcomesreflectsacausativerelationshiphasbeendifficultin
somecases.[83]Inothercases,theattributionofadverseoutcomestoantidepressantexposureseemsfairlyclear.
SSRIuseinpregnancyisassociatedwithanincreasedriskofspontaneousabortionofabout1.7fold.[84][85]MaternalSSRIusemaybeassociatedwithalowerriskforlate
pretermbirthforverypretermbirthandforcesareansection.[86]
Asystematicreviewoftheriskofmajorbirthdefectsinantidepressantexposedpregnanciesfoundasmallincrease(3%to24%)intheriskofmajormalformationsandariskof
cardiovascularbirthdefectsthatdidnotdifferfromnonexposedpregnancies.[87]Astudyoffluoxetineexposedpregnanciesfounda12%increaseintheriskofmajor
malformationsthatjustmissedstatisticalsignificance.[88]Otherstudieshavefoundanincreasedriskofcardiovascularbirthdefectsamongdepressedmothersnotundergoing
SSRItreatment,suggestingthepossibilityofascertainmentbias,e.g.thatworriedmothersmaypursuemoreaggressivetestingoftheirinfants.[89]Anotherstudyfoundnoincrease
incardiovascularbirthdefectsanda27%increasedriskofmajormalformationsinSSRIexposedpregnancies.[85]
TheFDAissuedastatementonJuly19,2006statingnursingmothersonSSRIsmustdiscusstreatmentwiththeirphysicians.However,themedicalliteratureonthesafetyof
SSRIshasdeterminedthatsomeSSRIslikeSertralineandParoxetineareconsideredsafeforbreastfeeding.[90][91][92]

Neonatalabstinencesyndrome
Severalstudieshavedocumentedneonatalabstinencesyndrome,asyndromeofneurological,gastrointestinal,autonomic,endocrineand/orrespiratorysymptomsamongalarge
minorityofinfantswithintrauterineexposure.Thesesyndromesareshortlived,butinsufficientlongtermdataisavailabletodeterminewhethertherearelongtermeffects.[93][94]
Persistentpulmonaryhypertension
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Persistentpulmonaryhypertension(PPHN)isaseriousandlifethreatening,butveryrare,lungconditionthatoccurssoonafterbirthofthenewborn.NewbornbabieswithPPHN
havehighpressureintheirlungbloodvesselsandarenotabletogetenoughoxygenintotheirbloodstream.About1to2babiesper1000babiesbornintheU.S.developPPHN
shortlyafterbirth,andoftentheyneedintensivemedicalcare.Itisassociatedwithabouta25%riskofsignificantlongtermneurologicaldeficits.[95]A2014metaanalysisfound
noincreasedriskofpersistentpulmonaryhypertensionassociatedwithexposuretoSSRI'sinearlypregnancyandaslightincreaseinriskassociateswithexposurelatein
pregnancy"anestimated286to351womenwouldneedtobetreatedwithanSSRIinlatepregnancytoresultinanaverageofoneadditionalcaseofpersistentpulmonary
hypertensionofthenewborn.".[96]Areviewpublishedin2012reachedconclusionsverysimilartothoseofthe2014study.[97]
Neuropsychiatriceffectsinoffspring
Accordingtoa2015reviewavailabledatafoundthat"somesignalexistssuggestingthatantenatalexposuretoSSRIsmayincreasetheriskofASDs(autismspectrum
disorders)"[98]eventhoughalargecohortstudypublishedin2013[99]andacohortstudyusingdatafromFinland'snationalregisterbetweentheyears1996and2010and
publishedin2016foundnosignificantassociationbetweenSSRIuseandautisminoffspring.[100]The2016FinlandstudyalsofoundnoassociationwithADHD,butdidfindan
associationwithincreasedratesofdepressiondiagnosesinearlyadolescence.[100]

Overdose
SSRIsappearsaferinoverdosewhencomparedwithtraditionalantidepressants,suchasthetricyclicantidepressants.Thisrelativesafetyissupportedbothbycaseseriesand
studiesofdeathspernumbersofprescriptions.[101]However,casereportsofSSRIpoisoninghaveindicatedthatseveretoxicitycanoccur[102]anddeathshavebeenreported
followingmassivesingleingestions,[103]althoughthisisexceedinglyuncommonwhencomparedtothetricyclicantidepressants.[101]
BecauseofthewidetherapeuticindexoftheSSRIs,mostpatientswillhavemildornosymptomsfollowingmoderateoverdoses.Themostcommonlyreportedsevereeffect
followingSSRIoverdoseisserotoninsyndromeserotonintoxicityisusuallyassociatedwithveryhighoverdosesormultipledrugingestion.[104]Otherreportedsignificanteffects
includecoma,seizures,andcardiactoxicity.[101]
TheSSRIs,indecreasingtoxicityinoverdose,canbelistedasfollows:[105]
Citalopram(duetothepotentialforQTintervalprolongation)
Fluvoxamine
Escitalopram
Paroxetine
Sertraline
Fluoxetine

Contraindicationsanddruginteractions
ThefollowingdrugsmayprecipitateserotoninsyndromeinpeopleonSSRIs:[106][107]
Linezolid
Monoamineoxidaseinhibitors(MAOIs)includingmoclobemide,phenelzine,tranylcypromine,selegilineandmethyleneblue
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Lithium
Sibutramine
MDMA(ecstasy)
Dextromethorphan
Tramadol
Pethidine/meperidine
St.John'swort
Yohimbe
Tricyclicantidepressants(TCAs)
Serotoninnorepinephrinereuptakeinhibitors(SNRIs)
Buspirone
Triptan
Mirtazapine
PainkillersoftheNSAIDsdrugfamilymayinterfereandreduceefficiencyofSSRIsandmaycompoundtheincreasedriskofgastrointestinalbleedscausedbySSRI
use.[56][58][108]NSAIDsinclude:
Aspirin
Ibuprofen(Advil,Nurofen)
Naproxen(Aleve)
ThereareanumberofpotentialpharmacokineticinteractionsbetweenthevariousindividualSSRIsandothermedications.MostofthesearisefromthefactthateverySSRIhas
theabilitytoinhibitcertainP450cytochromes.[109][110]
DrugName CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 CYP2B6
Citalopram

Escitalopram 0

Fluoxetine

++

+/++

+++

Fluvoxamine +++

++

+++

Paroxetine

+++

+++

Sertraline

+/++

Legend:
0noinhibition.
+mildinhibition.
++moderateinhibition.
+++stronginhibition.

Listofagents
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Drugsinthisclassinclude:
Mostcommon:
citalopram
escitalopram
fluoxetine
fluvoxamine
paroxetine
sertraline
Other:
dapoxetine
indalpine(discontinued)
zimelidine(discontinued)
cericlamine(reachedphaseIIIdiscontinuedin1999)
Panuramine
Selectiveserotoninreuptakeinhibitors(SSRIs)

Citalopram

Dapoxetine

Panuramine

Fluoxetine
Escitalopram

Fluvoxamine

Cericlamine

Indalpine
Paroxetine

Femoxetine

Sertraline

Zimelidine

Relatedagents
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SSRIsformasubclassofserotoninuptakeinhibitors,whichincludesothernonselectiveinhibitorsaswell.Theserotonergicserotoninnorepinephrinereuptakeinhibitorsand
serotoninnorepinephrinedopaminereuptakeinhibitorsarealsocommonlyusedasantidepressants.

Mechanismofaction
Inthebrain,messagesarepassedfromanervecelltoanotherviaachemicalsynapse,asmallgapbetweenthecells.Thepresynapticcellthatsendstheinformationreleases
neurotransmittersincludingserotoninintothatgap.Theneurotransmittersarethenrecognizedbyreceptorsonthesurfaceoftherecipientpostsynapticcell,whichuponthis
stimulation,inturn,relaysthesignal.About10%oftheneurotransmittersarelostinthisprocesstheother90%arereleasedfromthereceptorsandtakenupagainbymonoamine
transportersintothesendingpresynapticcell,aprocesscalledreuptake.
SSRIsinhibitthereuptakeofserotonin.Asaresult,theserotoninstaysinthesynapticgaplongerthanitnormallywould,andmayrepeatedlystimulatethereceptorsofthe
recipientcell.Intheshortrun,thisleadstoanincreaseinsignalingacrosssynapsesinwhichserotoninservesastheprimaryneurotransmitter.Onchronicdosing,theincreased
occupancyofpresynapticserotoninreceptorssignalsthepresynapticneurontosynthesizeandreleaselessserotonin.Serotoninlevelswithinthesynapsedrop,thenriseagain,
ultimatelyleadingtodownregulationofpostsynapticserotoninreceptors.[111]Other,indirecteffectsmayincludeincreasednorepinephrineoutput,increasedneuronalcyclicAMP
levels,andincreasedlevelsofregulatoryfactorssuchasBDNFandCREB.[112]Owingtothelackofawidelyacceptedcomprehensivetheoryofthebiologyofmooddisorders,
thereisnowidelyacceptedtheoryofhowthesechangesleadtothemoodelevatingandantianxietyeffectsofSSRIs.

Pharmacogenetics
LargebodiesofresearcharedevotedtousinggeneticmarkerstopredictwhetherpatientswillrespondtoSSRIsorhavesideeffectsthatwillcausetheirdiscontinuation,although
thesetestsarenotyetreadyforwidespreadclinicaluse.[113]

SSRIsversusTCAs
SSRIsaredescribedas'selective'becausetheyaffectonlythereuptakepumpsresponsibleforserotonin,asopposedtoearlierantidepressants,whichaffectothermonoamine
neurotransmittersaswell,andasaresult,SSRIshavefewersideeffects.
ThereappearstobenosignificantdifferenceineffectivenessbetweenSSRIsandtricyclicantidepressants,whichwerethemostcommonlyusedclassofantidepressantsbeforethe
developmentofSSRIs.[114]However,SSRIshavetheimportantadvantagethattheirtoxicdoseishigh,and,therefore,theyaremuchmoredifficulttouseasameanstocommit
suicide.Further,theyhavefewerandmildersideeffects.Tricyclicantidepressantsalsohaveahigherriskofseriouscardiovascularsideeffects,whichSSRIslack.
SSRIsactonsignalpathwayssuchascAMP(CyclicAMP)onthepostsynapticneuronalcell,whichleadstothereleaseofBrainDerivedNeurotrophicFactor(BDNF).BDNF
enhancesthegrowthandsurvivalofcorticalneuronsandsynapses.[112]

Societyandculture
Controversy

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AstudyexaminingpublicationofresultsfromFDAevaluatedantidepressantsconcludedthatthosewithfavorableresultsweremuchmorelikelytobepublishedthanthosewith
negativeresults.[115]
DavidHealyhasarguedthatwarningsignswereavailableformanyyearspriortoregulatoryauthoritiesmovingtoputwarningsonantidepressantlabelsthattheymightcause
suicidalthoughts.[116]Atthetimethesewarningswereadded,othersarguedthattheevidenceforharmremainedunpersuasive[117][118]andotherscontinuedtodosoafterthe
warningswereadded.[119][120]

Seealso
DevelopmentanddiscoveryofSSRIdrugs
Dopaminereuptakeinhibitor(DRI)
Noradrenergicandspecificserotonergicantidepressant(NaSSA)
Norepinephrinedopaminereuptakeinhibitor(NDRI)
Norepinephrinereuptakeinhibitor(NRI)
Serotoninantagonistandreuptakeinhibitor
Serotoninnorepinephrinedopaminereuptakeinhibitor(SNDRI)
Serotoninnorepinephrinereuptakeinhibitor(SNRI)
Serotoninreleasingagent(SRA)
Serotoninreuptakeinhibitor(SRI)
Traceamineassociatedreceptor1(TAAR1)

References
1.Barlow,DavidH.Durand,V.Mark(2009)."Chapter7:MoodDisordersandSuicide".
AbnormalPsychology:AnIntegrativeApproach(Fifthed.).Belmont,CA:Wadsworth
CengageLearning.p.239.ISBN0495095567.OCLC192055408.
2.http://pi.lilly.com/us/prozac.pdfpage20
3.PreskornSH,RossR,StangaCY(2004)."SelectiveSerotoninReuptakeInhibitors".In
SheldonH.Preskorn,HohnP.Feighner,ChristinaY.Stanga,RuthRoss.Antidepressants:
Past,PresentandFuture.Berlin:Springer.pp.24162.ISBN9783540430544.
4.FournierJC,DeRubeisRJ,HollonSD,DimidjianS,AmsterdamJD,SheltonRC,Fawcett
J(January2010)."AntidepressantDrugEffectsandDepressionSeverity".JAMA.303(1):
4753.doi:10.1001/jama.2009.1943.PMC3712503 .PMID20051569.
5.Kramer,Peter(7Sep2011)."InDefenseofAntidepressants".TheNewYorkTimes.
Retrieved13July2011.
6.PiesR(April2010)."AntidepressantsWork,SortofOurSystemofCareDoesNot".
JournalofClinicalPsychopharmacology.30(2):101104.
doi:10.1097/JCP.0b013e3181d52dea.PMID20520282.
7.Medford,Nick."Understandingandtreatingdepersonalizationdisorder".Advancesin
PsychiatricTreatment(2005).Retrieved20111111.
8."www.nice.org.uk"(PDF).Archivedfromtheoriginal(PDF)onSeptember28,2013.
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor

9.KirschI,DeaconBJ,HuedoMedinaTB,ScoboriaA,MooreTJ,JohnsonBT(February
2008)."InitialSeverityandAntidepressantBenefits:AMetaAnalysisofDataSubmittedto
theFoodandDrugAdministration".PLoSMedicine.5(2):e45.
doi:10.1371/journal.pmed.0050045.PMC2253608 .PMID18303940.
10.HorderJ,MatthewsP,WaldmannR(June2010)."Placebo,ProzacandPLoS:significant
lessonsforpsychopharmacology".JournalofPsychopharmacology.25(10):127788.
doi:10.1177/0269881110372544.PMID20571143.
11.FountoulakisKN,MllerHJ(August2010)."Efficacyofantidepressants:areanalysisand
reinterpretationoftheKirschdata".TheInternationalJournalof
Neuropsychopharmacology.14(3):18.doi:10.1017/S1461145710000957.
PMID20800012.
12.Depression:TheNICEGuidelineontheTreatmentandManagementofDepressionin
Adults(UpdatedEdition)(PDF).RCPsychPublications.2010.ISBN1904671853.
13.GibbonsRD,HurK,BrownCH,DavisJM,MannJJ(June2012)."Benefitsfrom
antidepressants:synthesisof6weekpatientleveloutcomesfromdoubleblindplacebo
controlledrandomizedtrialsoffluoxetineandvenlafaxine".ArchivesofGeneral
Psychiatry.69(6):5729.doi:10.1001/archgenpsychiatry.2011.2044.PMC3371295 .
PMID22393205.
11/15

12/7/2016

SelectiveserotoninreuptakeinhibitorWikipedia

14.FournierJC,DeRubeisRJ,HollonSD,DimidjianS,AmsterdamJD,SheltonRC,Fawcett
J(January2010)."Antidepressantdrugeffectsanddepressionseverity:apatientlevel
metaanalysis".JAMA.303(1):4753.doi:10.1001/jama.2009.1943.PMC3712503 .
PMID20051569.
15.GartlehnerG,HansenRA,MorganLC,ThalerK,LuxL,VanNoordM,MagerU,Thieda
P,GaynesBN,WilkinsT,StrobelbergerM,LloydS,ReichenpfaderU,LohrKN
(December2011)."Comparativebenefitsandharmsofsecondgenerationantidepressants
fortreatingmajordepressivedisorder:anupdatedmetaanalysis".AnnalsofInternal
Medicine.155(11):77285.doi:10.7326/000348191551120111206000009.
PMID22147715.
16.HetrickSE,McKenzieJE,CoxGR,SimmonsMB,MerrySN(Nov14,2012)."Newer
generationantidepressantsfordepressivedisordersinchildrenandadolescents.".The
CochraneDatabaseofSystematicReviews.11:CD004851.
doi:10.1002/14651858.cd004851.pub3.PMID23152227.
17."www.nice.org.uk"(PDF).Retrieved20130220.
18.KapczinskiF,LimaMS,SouzaJS,SchmittR(2003).Kapczinski,FlavioFK,ed.
"Antidepressantsforgeneralizedanxietydisorder".TheCochraneDatabaseofSystematic
Reviews(2):CD003592.doi:10.1002/14651858.CD003592.PMID12804478.
19."Obsessivecompulsivedisorder:Coreinterventionsinthetreatmentofobsessive
compulsivedisorderandbodydysmorphicdisorder"(PDF).November2005
20.ArrollB,ElleyCR,FishmanT,GoodyearSmithFA,KenealyT,BlashkiG,KerseN,
MacgillivrayS(2009).Arroll,Bruce,ed."Antidepressantsversusplacebofordepression
inprimarycare".TheCochraneDatabaseofSystematicReviews(3):CD007954.
doi:10.1002/14651858.CD007954.PMID19588448.
21.https://web.archive.org/web/20130413110435/http://www.medscape.com/viewarticle/570825
.ArchivedfromtheoriginalonApril13,2013.Missingorempty|title=(help)
22.FinebergNA,BrownA,ReghunandananS,PampaloniI(2012)."Evidencebased
pharmacotherapyofobsessivecompulsivedisorder".TheInternationalJournalof
Neuropsychopharmacology.15(8):117391.doi:10.1017/S1461145711001829.
PMID22226028.
23."Sertralineprescribinginformation"(PDF).Retrieved20150130.
24."Paroxetineprescribinginformation"(PDF).Retrieved20150130.
25."Eatingdisordersinover8s:management"(PDF).NICE.January2004.
26."NationalGuidelineClearinghouse|Practiceguidelineforthetreatmentofpatientswith
eatingdisorders".
27.FlamentMF,BissadaH,SpettigueW(March2012)."Evidencebasedpharmacotherapyof
eatingdisorders".TheInternationalJournalofNeuropsychopharmacology.15(2):189
207.doi:10.1017/S1461145711000381.PMID21414249.
28.MeadGE,HsiehCF,LeeR,KutlubaevMA,ClaxtonA,HankeyGJ,HackettML(2012).
Mead,GillianE,ed."Selectiveserotoninreuptakeinhibitors(SSRIs)forstrokerecovery".
TheCochraneDatabaseofSystematicReviews.11:CD009286.
doi:10.1002/14651858.CD009286.pub2.PMID23152272.
29.WaldingerMD(November2007)."Prematureejaculation:stateoftheart".TheUrologic
ClinicsofNorthAmerica.34(4):5919,viiviii.doi:10.1016/j.ucl.2007.08.011.
PMID17983899.
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor

30.WuQ,BencazAF,HentzJG,CrowellMD(January2012)."Selectiveserotoninreuptake
inhibitortreatmentandriskoffractures:ametaanalysisofcohortandcasecontrol
studies".OsteoporosisInternational.23(1):36575.doi:10.1007/s0019801117788.
PMID21904950.
31.StahlSM,LonnenAJ(2011)."TheMechanismofDruginducedAkathsia".CNS
Spectrums.PMID21406165.
32.LaneRM(1998)."SSRIinducedextrapyramidalsideeffectsandakathisia:implications
fortreatment".JournalofPsychopharmacology.12(2):192214.
doi:10.1177/026988119801200212.PMID9694033.
33.KoliscakLP,MakelaEH(2009)."Selectiveserotoninreuptakeinhibitorinducedakathisia".
JournaloftheAmericanPharmacistsAssociation.49(2):e2836quize378.
doi:10.1331/JAPhA.2009.08083.PMID19289334.
34.LeoRJ(1996)."Movementdisordersassociatedwiththeserotoninselectivereuptake
inhibitors".TheJournalofClinicalPsychiatry.57(10):44954.
doi:10.4088/JCP.v57n1002.PMID8909330.
35.September23,2012."SSRIsandDepression".Emedicinehealth.com.Retrieved
20120923.
36.Bahrick,Audrey(2008)."PersistenceofSexualDysfunctionSideEffectsafter
DiscontinuationofAntidepressantMedications:EmergingEvidence"(PDF).TheOpen
PsychologyJournal.1:4250.doi:10.2174/1874350100801010042.Retrieved30January
2014.
37.Taylor,MJRudkin,LBullemorDay,PLubin,JChukwujekwu,CHawton,K(31May
2013)."Strategiesformanagingsexualdysfunctioninducedbyantidepressantmedication.".
TheCochraneDatabaseofSystematicReviews.5:CD003382.
doi:10.1002/14651858.CD003382.pub3.PMID23728643.
38.Kennedy,SHRizvi,S(April2009)."Sexualdysfunction,depression,andtheimpactof
antidepressants.".JournalofClinicalPsychopharmacology.29(2):15764.
doi:10.1097/jcp.0b013e31819c76e9.PMID19512977.
39.Waldinger,MD(2015)."Psychiatricdisordersandsexualdysfunction.".Handbookof
ClinicalNeurology/editedbyDavidB.VoduekandFranoisBoller.Handbookof
ClinicalNeurology.130:46989.doi:10.1016/B9780444632470.000274.
ISBN9780444632470.PMID26003261.
40.http://pi.lilly.com/us/prozac.pdfPage14.
41."Onehundredandtwentycasesofenduringsexualdysfunctionfollowingtreatment".
ResearchGate.doi:10.3233/JRS140617.Retrieved20160130.
42.Gitlin,M.J.(19940901)."Psychotropicmedicationsandtheireffectsonsexualfunction:
diagnosis,biology,andtreatmentapproaches".TheJournalofClinicalPsychiatry.55(9):
406413.ISSN01606689.PMID7929021.
43."AntidepressantAssociatedSexualDysfunction:APotentiallyAvoidableTherapeutic
ChallengePrimaryPsychiatry".PrimaryPsychiatry.Retrieved20160130.
44.Clayton,AnitaH.(2003)."AntidepressantAssociatedSexualDysfunction:APotentially
AvoidableTherapeuticChallenge".PrimaryPsychiatry.10(1):5561.
45.KanalyKA,BermanJR(December2002)."SexualsideeffectsofSSRImedications:
potentialtreatmentstrategiesforSSRIinducedfemalesexualdysfunction".Current
Women'sHealthReports.2(6):40916.PMID12429073.
12/15

12/7/2016

SelectiveserotoninreuptakeinhibitorWikipedia

46.BalonR(2006)."SSRIAssociatedSexualDysfunction".TheAmericanJournalof
Psychiatry.163(9):15049quiz1664.doi:10.1176/appi.ajp.163.9.1504.PMID16946173.
47.KoyuncuH,SerefogluEC,OzdemirAT,HellstromWJ(September2012)."Deleterious
effectsofselectiveserotoninreuptakeinhibitortreatmentonsemenparametersinpatients
withlifelongprematureejaculation".Int.J.Impot.Res.24(5):1713.
doi:10.1038/ijir.2012.12.PMID22573230.
48.OhSW,KimJ,MyungSK,HwangSS,YoonDH(Mar20,2014)."AntidepressantUseand
RiskofCoronaryHeartDisease:MetaAnalysisofObservationalStudies.".British
JournalofClinicalPharmacology.78(4):72737.doi:10.1111/bcp.12383.
PMID24646010.
49.HuybrechtsKF,PalmstenK,AvornJ,CohenLS,HolmesLB,FranklinJM,MogunH,
LevinR,KowalM,SetoguchiS,HernndezDazS(2014)."AntidepressantUsein
PregnancyandtheRiskofCardiacDefects".NewEnglandJournalofMedicine.370(25):
23972407.doi:10.1056/NEJMoa1312828.ISSN00284793.PMID24941178.
50.GoldbergRJ(1998)."Selectiveserotoninreuptakeinhibitors:infrequentmedicaladverse
effects".ArchivesofFamilyMedicine.7(1):7884.doi:10.1001/archfami.7.1.78.
PMID9443704.
51.FDA."FDADrugSafety".
52.Citalopramandescitalopram:QTintervalprolongationnewmaximumdailydose
restrictions(includinginelderlypatients),contraindications,andwarnings(http://www.mhr
a.gov.uk/Safetyinformation/DrugSafetyUpdate/CON137769).FromMedicinesand
HealthcareProductsRegulatoryAgency.Articledate:December2011
53."ref2"(PDF).Retrieved20120923.
54.PacherP,UngvariZ,NanasiPP,FurstS,KecskemetiV(Jun1999)."Speculationson
differencebetweentricyclicandselectiveserotoninreuptakeinhibitorantidepressantson
theircardiaceffects.Isthereany?".CurrentMedicinalChemistry.6(6):46980.
PMID10213794.
55.WeinriebRM,AuriacombeM,LynchKG,LewisJD(March2005)."Selectiveserotonin
reuptakeinhibitorsandtheriskofbleeding".ExpertOpiniononDrugSafety.4(2):337
44.doi:10.1517/14740338.4.2.337.PMID15794724.
56.Taylor,DCarol,PShitij,K(2012).TheMaudsleyprescribingguidelinesinpsychiatry.
WestSussex:WileyBlackwell.ISBN9780470979693.
57.AndradeC,SandarshS,ChethanKB,NageshKS(December2010)."SerotoninReuptake
InhibitorAntidepressantsandAbnormalBleeding:AReviewforCliniciansanda
ReconsiderationofMechanisms".TheJournalofClinicalPsychiatry.71(12):15651575.
doi:10.4088/JCP.09r05786blu.PMID21190637.
58.deAbajoFJ,GarcaRodrguezLA(July2008)."Riskofuppergastrointestinaltract
bleedingassociatedwithselectiveserotoninreuptakeinhibitorsandvenlafaxinetherapy:
interactionwithnonsteroidalantiinflammatorydrugsandeffectofacidsuppressing
agents".ArchivesofGeneralPsychiatry.65(7):795803.doi:10.1001/archpsyc.65.7.795.
PMID18606952.
59.HackamDG,MrkobradaM(2012)."Selectiveserotoninreuptakeinhibitorsandbrain
hemorrhage:ametaanalysis".Neurology.79(18):18625.
doi:10.1212/WNL.0b013e318271f848.PMID23077009.

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor

60.SerebruanyVL(February2006)."Selectiveserotoninreuptakeinhibitorsandincreased
bleedingrisk:arewemissingsomething?".TheAmericanJournalofMedicine.119(2):
1136.doi:10.1016/j.amjmed.2005.03.044.PMID16443409.
61.HalperinD,ReberG(2007)."Influenceofantidepressantsonhemostasis".Dialoguesin
ClinicalNeuroscience.9(1):4759.PMC3181838 .PMID17506225.
62.AndradeC,SandarshS,ChethanKB,NageshKS(2010)."Serotoninreuptakeinhibitor
antidepressantsandabnormalbleeding:areviewforcliniciansandareconsiderationof
mechanisms".TheJournalofClinicalPsychiatry.71(12):156575.
doi:10.4088/JCP.09r05786blu.PMID21190637.
63.deAbajoFJ(2011)."Effectsofselectiveserotoninreuptakeinhibitorsonplateletfunction:
mechanisms,clinicaloutcomesandimplicationsforuseinelderlypatients".Drugs&
Aging.28(5):34567.doi:10.2165/1158934000000000000000.PMID21542658.
64."PsychiatryOnline|APAPracticeGuidelines|PracticeGuidelinefortheTreatmentof
PatientsWithMajorDepressiveDisorder,ThirdEdition".
65.RenoirT(2013)."Selectiveserotoninreuptakeinhibitorantidepressanttreatment
discontinuationsyndrome:areviewoftheclinicalevidenceandthepossiblemechanisms
involved".FrontiersinPharmacology.4:45.doi:10.3389/fphar.2013.00045.
PMC3627130 .PMID23596418.
66.StoneMB,JonesML(20061117)."Clinicalreview:relationshipbetweenantidepressant
drugsandsuicidalbehaviorinadults"(PDF).OverviewforDecember13Meetingof
PsychopharmacologicDrugsAdvisoryCommittee(PDAC).FDA.pp.1174.Retrieved
20070922.
67.LevensonM,HollandC(20061117)."StatisticalEvaluationofSuicidalityinAdults
TreatedwithAntidepressants"(PDF).OverviewforDecember13Meetingof
PsychopharmacologicDrugsAdvisoryCommittee(PDAC).FDA.pp.75140.Retrieved
20070922.
68.OlfsonM,MarcusSC,ShafferD(August2006)."Antidepressantdrugtherapyandsuicide
inseverelydepressedchildrenandadults:Acasecontrolstudy".ArchivesofGeneral
Psychiatry.63(8):86572.doi:10.1001/archpsyc.63.8.865.PMID16894062.
69.HammadTA(20040816)."Reviewandevaluationofclinicaldata.Relationshipbetween
psychiatricdrugsandpediatricsuicidalbehavior"(PDF).FDA.pp.42115.Retrieved
20080529.
70."AntidepressantUseinChildren,Adolescents,andAdults".
71."FDAMedicationGuideforAntidepressants"(PDF).Retrieved20140605.
72.CoxGR,CallahanP,ChurchillR,HunotV,MerrySN,ParkerAG,HetrickSE(2012).
"Psychologicaltherapiesversusantidepressantmedication,aloneandincombinationfor
depressioninchildrenandadolescents".CochraneDatabaseSystRev.11:CD008324.
doi:10.1002/14651858.CD008324.pub2.PMID23152255.
73."www.nice.org.uk"(PDF).
74.CoxGR,CallahanP,ChurchillR,HunotV,MerrySN,ParkerAG,HetrickSE(2012).
"Psychologicaltherapiesversusantidepressantmedication,aloneandincombinationfor
depressioninchildrenandadolescents".CochraneDatabaseSystRev.11:CD008324.
doi:10.1002/14651858.CD008324.pub2.PMID23152255.

13/15

12/7/2016

SelectiveserotoninreuptakeinhibitorWikipedia

75.MetaAnalysisofAggressionand/orHostilityRelatedEventsinChildrenandAdolescents
TreatedwithFluoxetineComparedwithPlacebo(http://www.liebertonline.com/doi/abs/10.1
089/cap.2006.0138)JournalofChildandAdolescentPsychopharmacology.October2007
17(5)713718.doi:10.1089/cap.2006.0138(https://dx.doi.org/10.1089%2Fcap.2006.0138).
76.GibbonsRD,HurK,BhaumikDK,MannJJ(November2006)."Therelationshipbetween
antidepressantprescriptionratesandrateofearlyadolescentsuicide".TheAmerican
JournalofPsychiatry.163(11):1898904.doi:10.1176/appi.ajp.163.11.1898.
PMID17074941.
77."ReportoftheCSMexpertworkinggrouponthesafetyofselectiveserotoninreuptake
inhibitorantidepressants"(PDF).MHRA.20041201.Retrieved20070925.
78."SelectiveSerotoninReuptakeInhibitors(SSRIs):OverviewofregulatorystatusandCSM
advicerelatingtomajordepressivedisorder(MDD)inchildrenandadolescentsincludinga
summaryofavailablesafetyandefficacydata".MHRA.20050929.Retrieved
20080529.
79.GunnellD,SaperiaJ,AshbyD(February2005)."Selectiveserotoninreuptakeinhibitors
(SSRIs)andsuicideinadults:metaanalysisofdrugcompanydatafromplacebocontrolled,
randomisedcontrolledtrialssubmittedtotheMHRA'ssafetyreview".BMJ(Clinical
ResearchEd.).330(7488):385.doi:10.1136/bmj.330.7488.385.PMC549105 .
PMID15718537.
80.FergussonD,DoucetteS,GlassKC,ShapiroS,HealyD,HebertP,HuttonB(February
2005)."Associationbetweensuicideattemptsandselectiveserotoninreuptakeinhibitors:
systematicreviewofrandomisedcontrolledtrials".BMJ(ClinicalResearchEd.).330
(7488):396.doi:10.1136/bmj.330.7488.396.PMC549110 .PMID15718539.
81.RihmerZ,AkiskalH(August2006)."Doantidepressantst(h)reat(en)depressives?Toward
aclinicallyjudiciousformulationoftheantidepressantsuicidalityFDAadvisoryinlightof
decliningnationalsuicidestatisticsfrommanycountries".JournalofAffectiveDisorders.
94(13):313.doi:10.1016/j.jad.2006.04.003.PMID16712945.
82.HallWD,LuckeJ(2006)."Howhavetheselectiveserotoninreuptakeinhibitor
antidepressantsaffectedsuicidemortality?".TheAustralianandNewZealandJournalof
Psychiatry.40(1112):94150.doi:10.1111/j.14401614.2006.01917.x.PMID17054562.
83.MalmH(December2012)."Prenatalexposuretoselectiveserotoninreuptakeinhibitorsand
infantoutcome".TherapeuticDrugMonitoring.34(6):60714.
doi:10.1097/FTD.0b013e31826d07ea.PMID23042258.
84.RahimiR,NikfarS,AbdollahiM(2006)."Pregnancyoutcomesfollowingexposureto
serotoninreuptakeinhibitors:ametaanalysisofclinicaltrials".ReproductiveToxicology
(Elmsford,N.Y.).22(4):571575.doi:10.1016/j.reprotox.2006.03.019.PMID16720091.
85.NikfarS,RahimiR,HendoieeN,AbdollahiM(2012)."Increasingtheriskofspontaneous
abortionandmajormalformationsinnewbornsfollowinguseofserotoninreuptake
inhibitorsduringpregnancy:Asystematicreviewandupdatedmetaanalysis".Daru:
JournalofFacultyofPharmacy,TehranUniversityofMedicalSciences.20(1):75.
doi:10.1186/200822312075.PMC3556001 .PMID23351929.
86.MalmH,SouranderA,GisslerM,GyllenbergD,HinkkaYliSalomkiS,McKeagueIW,
ArtamaM,BrownAS.PregnancyComplicationsFollowingPrenatalExposuretoSSRIsor
MaternalPsychiatricDisorders:ResultsFromPopulationBasedNationalRegisterData"
AmJPsychiatry2015Dec172(12):122432.doi:10.1176/appi.ajp.2015.14121575.Epub
2015Aug4.PMID26238606
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor

87.EinarsonTR,KennedyD,EinarsonA(2012)."Dofindingsdifferacrossresearchdesign?
Thecaseofantidepressantuseinpregnancyandmalformations".JournalofPopulation
TherapeuticsandClinicalPharmacology=JournaldelaThrapeutiquedesPopulationset
delaPharamcologieClinique.19(2):e33448.PMID22946124.
88.RigginL,FrankelZ,MorettiM,PupcoA,KorenG(April2013)."Thefetalsafetyof
fluoxetine:asystematicreviewandmetaanalysis".JournalofObstetricsandGynaecology
Canada.35(4):3629.PMID23660045.
89.KorenG,NordengHM(February2013)."Selectiveserotoninreuptakeinhibitorsand
malformations:caseclosed?".SeminarsinFetal&NeonatalMedicine.18(1):1922.
doi:10.1016/j.siny.2012.10.004.PMID23228547.
90."BreastfeedingUpdate:SDCBC'squarterlynewsletter".Breastfeeding.org.Archivedfrom
theoriginalonFebruary25,2009.Retrieved20100710.
91."UsingAntidepressantsinBreastfeedingMothers".kellymom.com.Retrieved20100710.
92.GentileS,RossiA,BellantuonoC(2007)."SSRIsduringbreastfeeding:spotlightonmilk
toplasmaratio".ArchivesofWomen'sMentalHealth.10(2):3951.doi:10.1007/s00737
00701730.PMID17294355.
93.FengerGrnJ,ThomsenM,AndersenKS,NielsenRG(September2011)."Paediatric
outcomesfollowingintrauterineexposuretoserotoninreuptakeinhibitors:asystematic
review".DanishMedicalBulletin.58(9):A4303.PMID21893008.
94.KievietN,DolmanKM,HonigA(2013)."Theuseofpsychotropicmedicationduring
pregnancy:howaboutthenewborn?".NeuropsychiatricDiseaseandTreatment.9:1257
1266.doi:10.2147/NDT.S36394.PMC3770341 .PMID24039427.
95."PersistentNewbornPulmonaryHypertension".
96.GrigoriadisS,VonderportenEH,MamisashviliL,TomlinsonG,DennisCL,KorenG,
SteinerM,MousmanisP,CheungA,RossLE(2014)."Prenatalexposureto
antidepressantsandpersistentpulmonaryhypertensionofthenewborn:systematicreview
andmetaanalysis".BMJ(ClinicalResearchEd.).348:f6932.doi:10.1136/bmj.f6932.
PMC3898424 .PMID24429387.
97.'tJongGW,EinarsonT,KorenG,EinarsonA(November2012)."Antidepressantusein
pregnancyandpersistentpulmonaryhypertensionofthenewborn(PPHN):asystematic
review".ReproductiveToxicology.34(3):2937.doi:10.1016/j.reprotox.2012.04.015.
PMID22564982.
98.GentileS.(2015)."Prenatalantidepressantexposureandtheriskofautismspectrum
disordersinchildren.ArewelookingatthefallofGods?".J.Affect.Disord.182:1327.
doi:10.1016/j.jad.2015.04.048.PMID25985383.Epub2015May6.
99.HviidA,MelbyeM,PasternakB(19December2013)."Useofselectiveserotoninreuptake
inhibitorsduringpregnancyandriskofautism".TheNewEnglandJournalofMedicine.
369(25):24062415.doi:10.1056/NEJMoa1301449.PMID24350950.Retrieved
18December2013.
100.HeliMalm,AlanS.Brownetal.(2016)."GestationalExposuretoSelectiveSerotonin
ReuptakeInhibitorsandOffspringPsychiatricDisorders:ANationalRegisterBased
Study".JournaloftheAmericanAcademyofChild&AdolescentPsychiatry.55:359366.
doi:10.1016/j.jaac.2016.02.013.
101.IsbisterGK,BoweSJ,DawsonA,WhyteIM(2004)."Relativetoxicityofselective
serotoninreuptakeinhibitors(SSRIs)inoverdose".JournalofToxicology.Clinical
Toxicology.42(3):27785.doi:10.1081/CLT120037428.PMID15362595.
14/15

12/7/2016

SelectiveserotoninreuptakeinhibitorWikipedia

102.BorysDJ,SetzerSC,LingLJ,ReisdorfJJ,DayLC,KrenzelokEP(1992)."Acute
fluoxetineoverdose:areportof234cases".TheAmericanJournalofEmergencyMedicine.
10(2):11520.doi:10.1016/07356757(92)90041U.PMID1586402.
103.OstrmM,ErikssonA,ThorsonJ,SpigsetO(1996)."Fataloverdosewithcitalopram".
Lancet.348(9023):33940.doi:10.1016/S01406736(05)645138.PMID8709713.
104.SporerKA(1995)."Theserotoninsyndrome.Implicateddrugs,pathophysiologyand
management".DrugSafety.13(2):94104.doi:10.2165/0000201819951302000004.
PMID7576268.
105.WhiteN,LitovitzT,ClancyC(December2008)."Suicidalantidepressantoverdoses:a
comparativeanalysisbyantidepressanttype"(PDF).JournalofMedicalToxicology.4(4):
238250.doi:10.1007/BF03161207.PMC3550116 .PMID19031375.
106.EnerRA,MeglatherySB,VanDeckerWA,GallagherRM(March2003)."Serotonin
SyndromeandOtherSerotonergicDisorders".PainMedicine.4(1):6374.
doi:10.1046/j.15264637.2003.03005.x.PMID12873279.
107.BoyerEW,ShannonMShannon,M(2005)."Theserotoninsyndrome"(PDF).TheNew
EnglandJournalofMedicine.352(11):11121120.doi:10.1056/NEJMra041867.
PMID15784664.
108.SolomonH.Snyder."J.L.WarnerSchmidtet.al"Antidepressanteffectsofselective
serotoninreuptakeinhibitors(SSRIs)areattenuatedbyantiinflammatorydrugsinmiceand
humans"PNAS2011".Pnas.org.Retrieved20120923.
109.Brunton,LChabner,BKnollman,B(2010).GoodmanandGilmansThe
PharmacologicalBasisofTherapeutics(12thed.).McGrawHillProfessional.ISBN978
0071624428.
110.Ciraulo,DAShader,RI(2011).PharmacotherapyofDepression(2nded.).Springer.
p.49.doi:10.1007/9781603274357.ISBN9781603274357.
111.Goodman,LouisS.(LouisSanford)Brunton,LaurenceL.Chabner,Bruce.Knollmann,
BjrnC.(2001).GoodmanandGilman'spharmacologicalbasisoftherapeutics.New
York:McGrawHill.pp.459461.ISBN0071624422.

112.Kolb,BryanandWishawIan.AnIntroductiontoBrainandBehavior.NewYork:Worth
Publishers2006,Print.
113.RasmussenTorvikLJ,McAlpineDD(2007)."GeneticscreeningforSSRIdrugresponse
amongthosewithmajordepression:greatpromiseandunseenperils".Depressionand
Anxiety.24(5):3507.doi:10.1002/da.20251.PMID17096399.
114.AndersonIM(April2000)."Selectiveserotoninreuptakeinhibitorsversustricyclic
antidepressants:ametaanalysisofefficacyandtolerability".JournalofAffective
Disorders.58(1):1936.doi:10.1016/S01650327(99)000920.PMID10760555.
115.TurnerEH,MatthewsAM,LinardatosE,TellRA,RosenthalR(January2008)."Selective
publicationofantidepressanttrialsanditsinfluenceonapparentefficacy".TheNew
EnglandJournalofMedicine.358(3):25260.doi:10.1056/NEJMsa065779.
PMID18199864.
116.HealyDAldredG(2005)."Antidepressantdruguseandtheriskofsuicide"(PDF).
InternationalReviewofPsychiatry.17:163172.doi:10.1080/09540260500071624.
117.LapierreYD(September2003)."Suicidalitywithselectiveserotoninreuptakeinhibitors:
Validclaim?".JPsychiatryNeurosci.28(5):3407.PMC193980 .PMID14517577.
118.KhanA,KhanS,KoltsR,BrownWA(2003)."SuicideratesinclinicaltrialsofSSRIs,
otherantidepressants,andplacebo:analysisofFDAreports.".Am.J.Psychiatry.160:790
2.doi:10.1176/appi.ajp.160.4.790.PMID12668373.
119.KaizarEE,GreenhouseJB,SeltmanH,KelleherK(2006)."Doantidepressantscause
suicidalityinchildren?ABayesianmetaanalysis".Clin.Trials.3(2):7390discussion
918.doi:10.1191/1740774506cn139oa.PMID16773951.
120.GibbonsRD,BrownCH,HurK,DavisJ,MannJJ(June2012)."Suicidalthoughtsand
behaviorwithantidepressanttreatment:reanalysisoftherandomizedplacebocontrolled
studiesoffluoxetineandvenlafaxine".Arch.Gen.Psychiatry.69(6):5807.
doi:10.1001/archgenpsychiatry.2011.2048.PMC3367101 .PMID22309973.

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