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21/7/2015 Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
http://www.uptodate.com.scihub.club/contents/clinicalmanifestationsdifferentialdiagnosisandinitialmanagementofpsychosisinadults?topicKey=P 1/16
OfficialreprintfromUpToDate www.uptodate.com.scihub.club2015UpToDate
AuthorsStephenMarder,MDMichaelDavis,MD,PhD
SectionEditorMurrayBStein,MD,MPH
DeputyEditorRichardHermann,MD
Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Jun2015.|Thistopiclastupdated:Sep22,2014.
INTRODUCTIONPsychosisisaconditionofthemindbroadlydefinedasalossofcontactwithreality.Itisestimatedthat13to23percentofpeopleexperiencepsychoticsymptomsatsomepointintheirlifetime,and1to4percentwillmeetcriteriaforapsychoticdisorder[1,2].
Psychoticsymptomscanincreasepatientsriskforharmingthemselvesorothersorbeingunabletomeettheirbasicneeds.Mostclinicianswillencounterpatientswithpsychosisandwillthusbenefitfromknowinghowtorecognizepsychoticsymptomsandmakeappropriateinitialevaluationandmanagementdecisions.Otherclinicians,particularlymentalhealthspecialists,willconductamorethoroughpatientassessment,considerthepatientsdifferentialdiagnosis,anddeterminethepatientsdiagnosistoguidelongtermtreatment.
Thistopicwillcharacterizedifferenttypesofpsychoticsymptoms,provideguidanceforformulatingadifferentialdiagnosis,andsuggestinitialevaluationandmanagementpractices.Issuesrelatedtoantipsychoticmedications,thetreatmentofspecificdisorders,andpsychosocialinterventionsarediscussedseparately.(See"Secondgenerationantipsychoticmedications:Pharmacology,administration,andcomparativesideeffects"and"Firstgenerationantipsychoticmedications:Pharmacology,administration,andcomparativesideeffects"and"Schizophrenia:Epidemiologyandpathogenesis"and"Schizophrenia:Clinicalmanifestations,course,assessment,anddiagnosis"and"Pharmacotherapyforschizophrenia:Longactinginjectableantipsychoticdrugs"and"Pharmacotherapyforschizophrenia:Acuteandmaintenancephasetreatment"and"Treatmentofcooccurringschizophreniaandsubstanceusedisorder"and"Treatmentresistantschizophrenia"and"Anxietyinschizophrenia"and"Depressioninschizophrenia"and"Pharmacotherapyforschizophrenia:Sideeffectmanagement"and"Briefpsychoticdisorder"and"Psychosocialinterventionsforschizophrenia".)
CLINICALMANIFESTATIONSPsychosiscanpresentwithawidevarietyofsignsandsymptoms[3],whicharedescribedbelow.
DelusionsDelusionsaredefinedasstronglyheldfalsebeliefsthatarenottypicalofthepatientsculturalorreligiousbackground.Theycanbecategorizedasbizarreornonbizarrebasedontheirplausibility(eg,abeliefthatfamilymembershavebeenreplacedbybodydoublesisbizarreandabeliefthataspouseishavinganaffairisnonbizarre).Frequentlyencounteredtypesofdelusionsinclude:
HallucinationsHallucinationscanbedefinedaswakefulsensoryexperiencesofcontentthatisnotactuallypresent.Theyaredifferentiatedfromillusions,whicharedistortionsormisinterpretationsofrealsensorystimuli.Whilehallucinationscanoccurinanyofthefivesensorymodalities,auditoryhallucinations(eg,hearingvoices)arethemostcommon,followedbyvisual,tactile,olfactory,andgustatoryhallucinations.Auditoryhallucinationscanpresentasspeech(includingspokencommandsorarunningcommentaryonthepatientsactions)orothersounds.Visualhallucinationscanrangefromrecognizableobjectstomoreunformedlightsorshadows.Olfactoryhallucinationsarefrequentlyofunpleasantodors.
Persecutorydelusions(eg,believingoneisbeingfollowedandharassedbygangs)Grandiosedelusions(eg,believingoneisabillionaireCEOwhoownscasinosaroundtheworld)Erotomanicdelusions(eg,believingafamousmoviestarisinlovewiththem)Somaticdelusions(eg,believingonessinuseshavebeeninfestedbyworms)Delusionsofreference(eg,believingdialogueonatelevisionprogramisdirectedspecificallytowardsthepatient)
Delusionsofcontrol(eg,believingonesthoughtsandmovementsarecontrolledbyplanetaryoverlords)
SciHub.
21/7/2015 Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
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ThoughtdisorganizationEvidenceforthoughtdisorganizationisderivedfrompatientspatternsofspeechduringtheinterview.Whiledisorganizedspeechisafrequentlyobservedsymptominpsychosis,itisnonspecificandcanalsobepresentindeliriumorotherneurologicalorcognitivedisorders.Commonlyobservedformsofthoughtdisorganizationinclude:
Agitation/aggressionAgitationisanacutestateofanxiety,heightenedemotionalarousal,andincreasedmotoractivity.Althoughnotspecifictopsychosis,untreatedpsychosisisassociatedwithanincreasedriskforagitationandaggressivebehaviors.Thesecansometimesleadtointentionalorunintentionalbodilyharmtoselforothers.Cliniciansshouldobservethepatientsbehaviors,includingbodylanguageandvoiceintonation,anduseappropriatesafetymeasuresfortheevaluation.(See"Assessmentandemergencymanagementoftheacutelyagitatedorviolentadult".)
DIFFERENTIALDIAGNOSISPsychoticsymptomscanbeassociatedwithawidevarietyofprimarypsychiatricandmedicalillnesses.Clinicalfeaturesofthepsychosisarenotpathognomonicforparticulardiagnoses,butcanprovideevidencesuggestiveofprimarypsychiatricversusmedicaletiologies.
Eachcaseshouldbeevaluatedthoroughlypossiblecausesforpsychosisshouldnotberuledoutbythesefeaturesalone.Athoroughhistory,physicalexamination,mentalstatusexamination,andadditionaltestsasindicatedcanhelpnarrowthedifferential,ruleoutpsychoseswithtreatableunderlyingcauses,andguidetheappropriateinterventionorreferral[4].
PrimarypsychiatricillnessesPsychiatricillnessesaregenerallyclassifiedbydiagnosticcriteriaestablishedbytheDSM5[5]ortheInternationalClassificationofDiseases(ICD,WorldHealthOrganization).Theseconstructsandcriteriaareperiodicallyrevisedbasedonresearchfindingsandexpertconsensus.
Alogia/povertyofcontentVerylittleinformationconveyedbyspeechThoughtblockingSuddenlylosingtrainofthought,exhibitedbyabruptinterruptioninspeechLooseningofassociationSpeechcontentnotableforideaspresentedinsequencethatarenotcloselyrelated
TangentialityAnswerstointerviewquestionsdivergingincreasinglyfromtopicbeingaskedabout(calledcircumstantialityifcontenteventuallyreturnstooriginaltopic)
ClangingorclangassociationUsingwordsinasentencethatarelinkedbyrhymingorphoneticsimilarity(eg,Ifelldownthewellsellbell.)
WordsaladRealwordsarelinkedtogetherincoherently,yieldingnonsensicalcontentPerseverationRepeatingwordsorideaspersistently,oftenevenafterinterviewtopichaschanged
Associatedwithprimarypsychiatric(psychotic)disorders:
FamilyhistoryoftenpresentInsidiousonsetOnsetinteenstomidthirtiesVariablepresentationAuditoryhallucinations
Associatedwithprimarymedicalcondition:
FamilyhistoryvariablypresentAcuteonsetOnsetinfortiesorolderPresentsingeneralmedicalorintensivecaresettingsNonauditoryhallucinations(eg,visual,tactile,olfactory)
SchizophreniaThisdisorderisdefinedbythepresenceofpsychoticsymptoms(eg,delusions,hallucinations,disorganizedspeech,grosslydisorganizedorcatatonicbehavior,ordiminishedemotionalexpressionorvolition)forasignificantportionoftimeduringaonemonthperiod(orlessifsuccessfullytreated).DSM5requiresthatthesymptomsbeassociatedwithadeclineinfunctioningorfailuretoachievetheexpectedleveloffunctioning.Signsofthedisturbancemustpersistforatleastsixmonths.
21/7/2015 Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
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Schizoaffectivedisorder,mooddisorderswithpsychoticfeatures,andattributiontosubstanceuseormedicalconditionsmustberuledout.Additionaldiagnosticrequirementsmustbemetifthereisahistoryofanotherchildhoodonsetpsychiatricdisorder.(See"Schizophrenia:Clinicalmanifestations,course,assessment,anddiagnosis".)
SchizophreniformdisorderThisdisordercanbeconsideredtohavesimilarsymptomaticpresentationasschizophrenia,exceptwithanepisodelastinggreaterthanonemonthbutlessthansixmonths.Inaddition,functionaldeclinedoesnotneedtobepresent.Schizoaffectivedisorder,mooddisorderswithpsychoticfeatures,andattributiontosubstanceuseormedicalcondition(s)mustberuledout.
SchizoaffectivedisorderThisdisorderisdefinedbytheindividualhavinganuninterruptedperiodofillnessduringwhichthereisamajormoodepisodeconcurrentwithpsychoticsymptomsaswellasdelusionsorhallucinationsfortwoormoreweeksintheabsenceofamajormoodepisodeduringthedurationoftheillness.Individualswiththisdisordermusthavesymptomsthatmeetcriteriaforamajormooddisorderforthemajorityofthetotaldurationoftheactiveandresidualportionsoftheillness.Disorderpresentationcannotbeattributabletosubstanceuseoranothermedicalcondition.
DelusionaldisorderThisdisorderischaracterizedbythepresenceofone(ormore)delusionswithadurationofonemonthorlongertheabsenceofmeetingcriteriaforschizophreniaalackofmarkedimpairmentinfunctioningorobviousbizarrebehaviorsandalackofattributiontomanicordepressiveepisodes,substances,othermedicalconditions,orbetterexplanationbyanothermentaldisorder.Thedelusionsareclassifiedaserotomanictype,grandiosetype,jealoustype,persecutorytype,somatictype,mixedtype,orunspecifiedtype,andbywhethertheyhavebizarrecontent.(See"Delusionalparasitosis:Epidemiology,clinicalpresentation,assessmentanddiagnosis"and"Treatmentofdelusionalparasitosis".)
BriefpsychoticdisorderThisdisorderischaracterizedbythepresenceofpsychoticsymptoms(eg,delusions,hallucinations,disorganizedspeech,orgrosslydisorganizedorcatatonicbehavior)withdurationonedayand
21/7/2015 Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
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SubstanceinducedpsychosesManyprescriptionmedicationsaswellasillicitsubstancescaninducetransientpsychoticsymptoms[6].TheDSM5definessubstance/medicationinducedpsychoticdisorderashavingthepresenceofdelusionsand/orhallucinationsduringorsoonafterintoxication,withdrawal,orexposuretoasubstance,withthedisturbancenotbeingbetterexplainedbyanothertypeofpsychoticdisorder.Thedisturbancecannotoccurexclusivelyduringthecourseofadeliriumandmustcausesignificantdistressorimpairmentinfunction.Atablelistsmajorsubstances,medications,andtoxinsthatcancausetransientpsychoses(table1).
PsychosesassociatedwithmedicalorneurologicalconditionsAlargenumberofmedicalillnessescanbeaccompaniedbypsychoticsymptoms.Presentinganddistinguishingcharacteristicsofthesediseasesaredescribedseparately.
DeliriumAdeliriumisanacutementaldisturbancecharacterizedbyproblemsofattention,confusion,anddisorientation.Itoftenpresentssuddenlyandfluctuatesinintensity.Deliriumfrequentlyisassociatedwithpsychoticsymptoms[7]andcanimprovefollowingantipsychotictreatment[8].Frequentcausesofdeliriumincludefluidorelectrolyteabnormalities,hypoglycemia,hypoxia,hypercapnea,infections,ormedications,substanceintoxicationorwithdrawalaredescribedinatable(table1).(See"Diagnosisofdeliriumandconfusionalstates".)
DIAGNOSTICEVALUATIONPrimarypsychiatricillnessesaregenerallydiagnosesofexclusion.Itisimportanttoconductathoroughevaluationofpsychoticsymptoms,particularlyoninitialpresentation[10],inordertoidentifytreatableunderlyingcauses.
InterviewTheinterviewshouldfocusonestablishingatimelineofsymptoms,apsychiatrichistoryincluding
mustbesevereenoughtocausemarkedimpairmentinsocialoroccupationalfunctioningortonecessitatehospitalizationtopreventharmtoselforothers,ortherearepsychoticfeatures.Theepisodesalsocannotbeattributabletosubstanceuseorothermedicalconditions.(See"Bipolardisorderinadults:Clinicalfeatures",sectionon'Psychosis'.)
EndocrinedisordersThyroiddisease,parathyroiddisease,adrenaldisease.(See"Diagnosisofhyperthyroidism"and"Primaryhyperparathyroidism:Clinicalmanifestations"and"Diagnosisofadrenalinsufficiencyinadults".)
HepaticandrenaldisordersHepaticencephalopathy,uremicencephalopathy.(See"Hepaticencephalopathyinadults:Clinicalmanifestationsanddiagnosis".)
InfectiousdiseaseHIV,syphilis,herpessimplexencephalitis,Lymedisease,priondisorders.(See"AcuteandearlyHIVinfection:Clinicalmanifestationsanddiagnosis"and"Pathogenesis,clinicalmanifestations,andtreatmentofearlysyphilis"and"Epidemiology,clinicalmanifestations,anddiagnosisofgenitalherpessimplexvirusinfection"and"DiagnosisofLymedisease"and"Diseasesofthecentralnervoussystemcausedbyprions".)
InflammatoryordemyelinatingdisordersAntiNMDAreceptorencephalitis,systemiclupuserythematosus,multiplesclerosis,leukodystrophies.(See"Paraneoplasticandautoimmuneencephalitis"and"Diagnosisofmultiplesclerosisinadults"and"Diagnosisanddifferentialdiagnosisofsystemiclupuserythematosusinadults"and"Differentialdiagnosisofacutecentralnervoussystemdemyelinationinchildren".)
MetabolicdisordersoracuteprocessesWilsonsdisease,acuteintermittentporphyria.(See"Wilsondisease:Clinicalmanifestations,diagnosis,andnaturalhistory"and"Porphyrias:Anoverview".)
Neurodegenerativedisorders[9]Alzheimersdisease,dementiawithLewybodies,Parkinsonsdisease,Huntingtonsdisease.(See"Evaluationofcognitiveimpairmentanddementia".)
NeurologicalHeadtrauma/traumaticbraininjury,spaceoccupyinglesions(tumors,cysts),seizuredisordersstroke.(See"Clinicalpresentationanddiagnosisofbraintumors".)
VitamindeficiencyVitaminB12deficiency.(See"DiagnosisandtreatmentofvitaminB12andfolatedeficiency".)
21/7/2015 Clinicalmanifestations,differentialdiagnosis,andinitialmanagementofpsychosisinadults
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priordiagnosesandtreatments,asubstanceusehistory,afamilyhistoryforpsychiatricillness,andacompletemedicalhistory.Disorganizedthinkingmaypreventthepatientfromgivingacoherenthistory.Additionally,patientsmaynotspontaneouslyreportpsychoticsymptomsanypatientinwhompsychoticsymptomsaresuspectedshouldbeaskeddirectlyaboutexperiencinghallucinations,suspiciousness,thoughtreading,specialmessagesfromTVorradio,andspecialpowersorabilities.Theclinicianshouldseekcorroborativesourcesofinformation,wheneverpossible,forevidenceofdelusionalorreferentialthinkingorotherunusualbehaviors.
MentalstatusexaminationAcompletementalstatusexaminationshouldbeconducted,payingparticularattentiontothepatientsappearance(grooming,hygiene)andgeneralbehaviors,moodandaffect,thoughtprocesses,evidenceforperceptualdisturbances(respondingtointernalstimuli),unusualthoughtcontent,attention,andmemoryfunction.
Commonmedicalworkup
Additionalteststoconsiderbasedonotherevidence
DifferentiationbetweenDSM5psychoticdisordersIfsubstances,medications,orunderlyingmedicalconditionshavebeenruledoutascausesforpsychoticsymptoms,aprimarypsychiatricdisordershouldbeconsidered.Whendeterminingthespecificdisorder,theassociatedsymptomsandtimecoursearetheprimarydifferentiators[11].
Ifclinicallysignificantmoodsymptomsarepresent(depressiveormanicsymptoms),thenmajordepressivedisorderwithpsychoticfeatures,bipolardisorderwithpsychoticfeatures,orschizoaffectivedisordershouldbeconsideredaspossibilities.Iftheindividualhasneverhadpsychoticsymptomswithoutmoodsymptoms,thediagnosiswillbemajordepressivedisorderwithpsychoticfeaturesorbipolardisorderwithpsychoticfeatures(dependingonahistoryofmanicsymptoms).Iftheindividualhasanoverlapofmoodsymptomswithpsychosisforthemajority(butnotall)ofthepsychoticillness,schizoaffectivedisorderwillbethelikelydiagnosis.
Ifthereisamorelimitedoverlapofpsychosisandmoodsymptoms(eithernooverlaporoverlaponlyforaminorityoftheillnessduration),thenbriefpsychoticdisorder,schizophreniformdisorder,schizophrenia,ordelusionaldisorderwouldbepossiblediagnoses.Thedurationofthepsychoticepisodewilldifferentiatebetweenbriefpsychoticdisorder(sixmonths).
Delusionaldisorderwouldbeconsideredifthepsychoticsymptomsarelimitedtodelusions,functioningisnotmarkedlyimpaired,andothersymptomsandbehaviorsassociatedwithschizophreniaarenotpresent.Schizotypalpersonalitydisorderwouldbeconsideredifthereisnoperiodofsignificantpersistentpsychotic
ChemistrypaneltoevaluatefordisturbancesinfluidorelectrolytesCompletebloodcounttoevaluateforinfectiousprocessesbloodcultureifindicatedHepaticfunctionpaneltoevaluateforliverabnormalitiesThyroidstimulatinghormoneleveltoruleoutthyroiddiseaseVDRL/RPRtoscreenforsyphilisUrinalysistoevaluateforurinarytractinfectionorotherabnormalitiesurinecultureifindicatedUrinedrugscreentoevaluateforrecentsubstanceuseVitaminB12levelstoevaluatefordeficiencyHIVtoevaluateforinfection
Computedtomography(CT)brainormagneticresonanceimaging(MRI)toevaluateforspaceoccupyinglesions,demyelinatingdisorders,orstroke
Electroencephalogram(EEG)LumbarpunctureHeavymetalscreenRheumatologicworkup(eg,antinuclearantibody,antiribosomeantibody,antiNMDAreceptorantibody)Hormonelevels
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symptomsandifthereisapervasivepatternofsocialandinterpersonaldeficitsmarkedbyacutediscomfortwith,andreducedcapacityfor,closerelationshipsaswellasbycognitiveorperceptualdistortionsandeccentricitiesofbehavior[11].
INITIALMANAGEMENTPatientswithpsychosisshouldbeevaluatedforagitation,riskofharmtothemselvesorothers,andtheirabilitytotakecareofthemselves.Patientsatriskofharmtothemselvesorothersmayneedtobehospitalized.Managementofagitatedpatientswithpsychosisisdescribedindetailseparately.Arapidlyactingfirstgenerationantipsychoticand/orarapidlyactingbenzodiazepinearesuggestedtosedateseverelyagitated,potentiallyviolentpatientswithpsychosis.(See"Assessmentandemergencymanagementoftheacutelyagitatedorviolentadult".)
Patientswithpsychosisandtheirfamiliesshouldbeeducatedabouttheirillnesses,risksassociatedwithpsychosis(eg,increasedriskofharmtothemselvesorothers),andrisksandsideeffectsassociatedwithantipsychoticmedications.Familiesorcaregiversshouldbeadvisedtoreduceenvironmentalstimulation,notarguewithdelusionalideas,andinteractwithpsychoticpatientsinacalmandgentlemanner.
Werecommendsymptomatictreatmentofpsychosiswithanantipsychoticmedication,evenifthepsychiatricdisorderormedicalconditionunderlyingthepsychosishasnotyetbeenestablished.Whileantipsychoticshavebeenmostextensivelystudiedinthetreatmentofschizophrenia,themedicationsappeartobebroadlyeffectiveforpsychoticsymptoms.Asexamples,metaanalyseshavefoundantipsychoticsareeffectiveinthetreatmentofpsychoticmaniainbipolardisorder[12],majordepressivedisorderwithpsychoticfeatures(whencombinedwithanantidepressant)[13],delirium[14],psychosisinParkinsonsdisease(clozapine)[15],andpsychosisofAlzheimersdisease[16].Thereislessofanevidencebasefortheiruseforrarergeneralmedicalconditions.Theuseandeffectivenessofantipsychoticdrugsforindividualdisordersanddiseasesarediscussedseparately.(See"Pharmacotherapyforschizophrenia:Acuteandmaintenancephasetreatment"and"Treatmentresistantschizophrenia"and"Briefpsychoticdisorder"and"Managementofneuropsychiatricsymptomsofdementia"and"Treatmentofdelusionalparasitosis"and"Treatmentofpostpartumpsychosis"and"Unipolarmajordepressionwithpsychoticfeatures:Acutetreatment"and"Guidelinesforprescribingclozapineinschizophrenia".)
Ifthepsychosisisassociatedwithamooddisorderexacerbation,theunderlyingmooddisordershouldbetreatedaswell.Ifthepsychosisisassociatedwithageneralmedicalcondition,antipsychotictherapyshouldbeaddedtotheappropriatetreatmentfortheunderlyingcondition.(See"Unipolarmajordepressionwithpsychoticfeatures:Acutetreatment"and"Bipolardisorderinadults:Pharmacotherapyforacutemaniaandhypomania".)
Antipsychoticdrugsaremosteffectiveatimprovingpositivepsychoticsymptoms(eg,hallucinations,delusions)whileofferinglessbenefitfornegativesymptoms(eg,bluntedaffect,avolition)orcognitivedeficitsthatarefrequentlyassociatedwithpsychosis.Antipsychoticscanreduceagitation[17]andmayreducesuiciderisk[18].Thebenefitsofantipsychoticsshould,however,beweighedagainsttheirrisksandpossiblesideeffects(table2).Appropriatestepsshouldbetakentomitigaterisk(eg,performingbaselineEKGsonolderadultpatientsorthosewithcardiachistoryandconsideringpossibilityforantipsychoticinducedQTcprolongation).(See"Pharmacotherapyforschizophrenia:Acuteandmaintenancephasetreatment",sectionon'Antipsychoticdrugefficacyandselection'.)
Withtheexceptionofclozapine,whichisusedfortreatmentresistantchronicpsychosis,thereisanabsenceofrigorousevidencethatanyoneantipsychoticdrugismoreeffectivethanotherantipsychotics.Thechoiceamongantipsychoticsisusuallymadeonthebasisofsideeffectprofile,cost,andformulationsavailable(table2).
Thedoseofmostantipsychoticdrugsshouldbetitratedfromaninitialdosetothetherapeuticrange,asdescribedinthetables,asquicklyastolerated(table2andtable3).Asanexample,risperidonecanbestartedat1to2mg/dayandtitratedtoatherapeuticdose(typically2to6mg/day).Ifasatisfactoryclinicalresponseisnotseenwithinsevendays,thedosecanbeincreasedin0.5to1mg/dayincrementstoamaximumof8mg/day.Ifthereisnoimprovementinpsychoticsymptomsaftertwoweeksofatherapeuticdose,adifferentantipsychoticshouldbeconsidered.Therecommendeddurationofantipsychotictherapyvariesaccordingto
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theunderlyingetiology:inchronicschizophrenia,antipsychoticsshouldbeofferedindefinitelytoreducerelapserisk[19]withtimelimitedpsychoses(suchasdelirium),antipsychotictherapycanbecontinuedfortwoweeksaftertheresolutionofsymptomsandthentaperedoffgradually.Theselectionamongantipsychoticdrugsandtheirdosingaredescribedindetailseparately.(See"Firstgenerationantipsychoticmedications:Pharmacology,administration,andcomparativesideeffects"and"Secondgenerationantipsychoticmedications:Pharmacology,administration,andcomparativesideeffects"and"Pharmacotherapyforschizophrenia:Acuteandmaintenancephasetreatment",sectionon'Acutephase'.)
ConsultationorreferraltoapsychiatristAnypatientwithaninitialonsetofpsychosisshouldbeevaluatedbyapsychiatrist,whetherintheformofanurgentoutpatientpsychiatricconsultationorinanemergencyroomoraninpatientconsultationbyahospitalpsychiatrist.Presentingpatientsengagedinlongitudinaltreatmentforapsychoticdisorder(orotherdisorder/illnesswithpsychosis)shouldbeevaluatedifheorsheis:
VoluntaryversusinvoluntarytreatmentPatientsatriskofharmtothemselvesorothersmayneedtobehospitalizedtoensuresafety.Evaluationandtreatmentforpsychosisshouldbevoluntarywheneverpossible,butthenatureoftheillnessmayleadpatientstofearoravoidtreatment.Inmoststates,dangerousnesstoselforothers,ortheinabilitytoprovideforone'sbasicneedsoffood,clothing,andshelter,issufficientcauseforinvoluntarytreatment.Thelegalmechanismforinitiatingthisdifferssignificantlybylegaljurisdiction.Clinicians,especiallythoseinemergencysettings,shouldbecomefamiliarwithinvoluntarytreatmentprocedureswithintheirlegaljurisdictions.Thelocalcommunitymentalhealthagencyorthenearestpsychiatricemergencyserviceshouldbeabletoassistwithinformation,legalforms,andotheraidinarranginginvoluntarycare.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthekeyword(s)ofinterest.)
SUMMARYANDRECOMMENDATIONS
ExperiencingamarkedincreaseinsymptomseverityDisplayingagitatedoraggressivebehaviorApossibledangertothemselvesorothersUnabletoprovidefortheirbasicneeds
Basicstopics(see"Schizophrenia:Epidemiologyandpathogenesis"and"Patientinformation:Tardivedyskinesia(TheBasics)"and"Patientinformation:Bipolardisorder(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Bipolardisorder(manicdepression)(BeyondtheBasics)")
Psychosisisaconditionofthemindbroadlydefinedasalossofcontactwithreality,whichoftenpresentswithdelusions,hallucinations,thoughtdisorganization,orunusualbehaviors.(See'Clinicalmanifestations'above.)
Patientswithpsychosisareatelevatedriskforagitatedandaggressivebehaviors,andsafetyprecautionsshouldbeemployed.(See'Agitation/aggression'aboveand'Mentalstatusexamination'above.)
Psychoticsymptomscanpresentinavarietyofpsychiatricandmedicalillnessesclinicalfeaturesarenotpathognomonicforparticulardiagnoses.(See'Psychosesassociatedwithmedicalorneurological
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REFERENCES
1. vanOsJ,HanssenM,BijlRV,VolleberghW.Prevalenceofpsychoticdisorderandcommunitylevelofpsychoticsymptoms:anurbanruralcomparison.ArchGenPsychiatry200158:663.
2. PerlJ,SuvisaariJ,SaarniSI,etal.LifetimeprevalenceofpsychoticandbipolarIdisordersinageneralpopulation.ArchGenPsychiatry200764:19.
3. SadockBJ,SadockVA,KaplanHI.KaplanandSadock'sComprehensiveTextbookofPsychiatry,LippincottWilliams&Wilkins,2009.Vol1.
4. SheitmanBB,LeeH,StrousR,LiebermanJA.Theevaluationandtreatmentoffirstepisodepsychosis.SchizophrBull199723:653.
5. AmericanPsychiatricAssociation.DiagnosticandStatisticalManualofMentalDisorders,FifthEdition(DSM5),AmericanPsychiatricAssociation,Arlington,VA2013.
6. FiorentiniA,VolonteriLS,DragognaF,etal.Substanceinducedpsychoses:acriticalreviewoftheliterature.CurrDrugAbuseRev20114:228.
7. WebsterR,HolroydS.Prevalenceofpsychoticsymptomsindelirium.Psychosomatics200041:519.8. LeentjensAF,RundellJ,RummansT,etal.Delirium:Anevidencebasedmedicine(EBM)monograph
forpsychosomaticmedicinepractice,comissionedbytheAcademyofPsychosomaticMedicine(APM)andtheEuropeanAssociationofConsultationLiaisonPsychiatryandPsychosomatics(EACLPP).JPsychosomRes201273:149.
9. JellingerKA.Cerebralcorrelatesofpsychoticsyndromesinneurodegenerativediseases.JCellMolMed201216:995.
10. FreudenreichO,SchulzSC,GoffDC.Initialmedicalworkupoffirstepisodepsychosis:aconceptualreview.EarlyIntervPsychiatry20093:10.
11. FirstMB.DSM5HandbookofDifferentialDiagnosis,AmericanPsychiatricPublishing,Arlington,VA2013.
conditions'above.)
Itisimportanttoperformathoroughhistory,physicalexamination,mentalstatusexamination,andworkupinordertoruleouttreatableunderlyingcausesofpsychosisandguideappropriatetherapy(See'Diagnosticevaluation'above.)
Patientswithpsychosisshouldbeevaluatedforagitation,riskofharmtothemselvesorothers,andtheirabilitytotakecareofthemselves.Patientsatriskofharmmayneedtobehospitalized.Severelyagitatedpatientswithpsychosismayimmediatesedationorotherrestraint.(See'Initialmanagement'aboveand"Assessmentandemergencymanagementoftheacutelyagitatedorviolentadult".)
Werecommendsymptomatictreatmentofpsychosiswithanantipsychoticmedication,evenifthespecificpsychiatricdisorderormedicalconditionunderlyingthepsychosishasnotyetbeenestablished(Grade1B).Asantipsychoticdrugsarelargelysimilarinefficacy,selectionamongthemistypicallymadeonthebasisofpatientpresentationandthemedicationssideeffectprofile,cost,andformulationsavailable(table2andtable3).(See'Initialmanagement'above.)
Asanexample,risperidonecanbestartedat1to2mg/dayandtitratedtoatherapeuticdose(typically2to6mg/day).Ifasatisfactoryclinicalresponseisnotachievedaftersevendays,thedosecanbeincreasedinincrementsof0.5to1mg/daytoamaximumof8mg/day.(See'Initialmanagement'above.)
Antipsychotictreatmentistypicallyadministeredincombinationwithtreatmentoftheunderlyingcondition.Thisappliestomedicalconditionscausingpsychosisaswellasamooddisorderexacerbationorsubstanceusedisorder.(See"Unipolarmajordepressionwithpsychoticfeatures:Acutetreatment"and"Bipolardisorderinadults:Pharmacotherapyforacutemaniaandhypomania"and"Pharmacotherapyforschizophrenia:Acuteandmaintenancephasetreatment"and"Treatmentofcooccurringschizophreniaandsubstanceusedisorder"and"Psychosocialinterventionsforschizophrenia"and"Briefpsychoticdisorder".)
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12. YildizA,VietaE,LeuchtS,BaldessariniRJ.Efficacyofantimanictreatments:metaanalysisofrandomized,controlledtrials.Neuropsychopharmacology201136:375.
13. WijkstraJ,LijmerJ,BurgerH,etal.Pharmacologicaltreatmentforpsychoticdepression.CochraneDatabaseSystRev201311:CD004044.
14. WangHR,WooYS,BahkWM.Atypicalantipsychoticsinthetreatmentofdelirium.PsychiatryClinNeurosci201367:323.
15. FrielingH,HillemacherT,ZiegenbeinM,etal.TreatingdopamimeticpsychosisinParkinson'sdisease:structuredreviewandmetaanalysis.EurNeuropsychopharmacol200717:165.
16. KatzI,deDeynPP,MintzerJ,etal.TheefficacyandsafetyofrisperidoneinthetreatmentofpsychosisofAlzheimer'sdiseaseandmixeddementia:ametaanalysisof4placebocontrolledclinicaltrials.IntJGeriatrPsychiatry200722:475.
17. CaasF.Managementofagitationintheacutepsychoticpatientefficacywithoutexcessivesedation.EurNeuropsychopharmacol200717Suppl2:S108.
18. RingbckWeitoftG,BerglundM,LindstrmEA,etal.Mortality,attemptedsuicide,rehospitalisationandprescriptionrefillforclozapineandotherantipsychoticsinSwedenaregisterbasedstudy.PharmacoepidemiolDrugSaf201423:290.
19. BuchananRW,KreyenbuhlJ,KellyDL,etal.The2009schizophreniaPORTpsychopharmacologicaltreatmentrecommendationsandsummarystatements.SchizophrBull201036:71.
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GRAPHICS
Substancesandmedicationswithcapacitytoinducepsychosis
Substanceormedication
Examples
Alcoholandsedatives/hypnotics
Alcohol(intoxicationorwithdrawal),barbituratesandbenzodiazepines(particularlywithdrawal)
Anabolicsteroids Testosterone,methyltestosterone
Analgesics Meperidine,pentazocine,indomethacin
Anticholinergics Atropine,scopolamine
Antidepressants Bupropion,othersiftriggeringamanicswitch
Antiepileptics Zonisamide,otheranticonvulsantsathighdoses
Antimalarial Mefloquine,chloroquine
Antiparkinsonian Levodopa,selegiline,amantadine,pramipexole,bromocriptine
Antivirals Abacavir,efavirenz,nevirapine,acyclovir
Cannabinoids Marijuana,syntheticcannabinoids(ie,"spice"),dronabinol
Cardiovascular Digoxin,disopyramide,propafenone,quinidine
Corticosteroids Prednisone,dexamethasone,etc
Hallucinogens LSD,PCP(phencyclidine),ketamine,psilocybincontainingmushrooms,mescaline,synthetic"designerdrugs"(eg,2CB,"NBomb"[25INBOMe]),salviadivinorum
Inhalants Toluene,butane,gasoline
Interferons Interferonalfa2a/2b
Overthecounter(OTC) Dextromethorphan(DXM),diphenhydramine,somedecongestants
Stimulants Cocaine,amphetamine/methamphetamine,methylphenidate,certaindietpills,"bathsalts"(MDPV,mephedrone),MDMA/ecstasy
Toxins Carbonmonoxide,organophosphates,heavymetals(eg,arsenic,manganese,mercury,thallium)
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Selectedadverseeffectsofantipsychoticmedicationsforschizophrenia
Weight
gain/diabetesmellitus
Hypercholesterolemia EPS/TD
Prolactinelevation Sedation
Firstgenerationagents
Chlorpromazine +++ +++ + ++ +++
Fluphenazine + + +++ +++ +
Haloperidol + + +++ +++ ++
Loxapine ++ ND ++ ++ ++
Perphenazine ++ ND ++ ++ ++
Pimozide + ND +++ ++ +
Thioridazine* ++ ND + +++ +++
Thiothixene ++ ND +++ ++ +
Trifluoperazine ++ ND +++ ++ +
Secondgenerationagents
Aripiprazole + ++ +
Asenapine ++ ++ ++ ++
Clozapine ++++ ++++ +++
Iloperidone ++ ++ +
Lurasidone + ++ ++
Olanzapine ++++ ++++ + + ++
Paliperidone +++ + ++ +++ +
Quetiapine +++ +++ ++
Risperidone +++ + +++ +++ +
Ziprasidone + + +
Adverseeffectsmaybedosedependent.
EPS:extrapyramidalsymptomsTD:tardivedyskinesiaND:nodata.*Thioridazineisalsoassociatedwithdosedependentretinitispigmentosa.Refertotext.Clozapinealsocausesgranulocytopeniaoragranulocytosisinapproximately1percentofpatientsrequiringregularbloodcellcountmonitoring.Clozapinehasbeenassociatedwithexcessriskofmyocarditisandvenousthromboemboliceventsincludingfatalpulmonaryembolism.TheseissuesareaddressedintheUpToDatetopicreviewofguidelinesforprescribingclozapinesectiononadverseeffects.
Adaptedwithspecialpermissionfrom:1. TreatmentGuidelinesfromTheMedicalLetter,June2013Vol.11(130):53.
www.medicalletter.org.Additionaldatafrom:
RummelKlugeC,etal.Headtoheadcomparisonsofmetabolicsideeffectsofsecondgenerationantipsychoticsinthetreatmentofschizophrenia:asystematicreviewandmetaanalysisSchizophrRes,November,2010123:225.
[1]
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DurnCE,AzermaiM,VanderSticheleRH.Systematicreviewofanticholinergicriskscalesinolderadults.EurJClinPharmacol201369:1485.
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Pharmacologyofantipsychotics:Dosing(adult),formulations,kineticsandpotentialfordruginteractions
Agent
Usualoraldoserange
(mg/day)
Initialoraldose(mg/day)
Usualmaximumoraldose(mg/day)*
Formulations
Halflifeafteroral
administration(hours)
Firstgenerationantipsychotics(FGAs)
Chlorpromazine 400to600 25to200 800 Tab,IM 30
Fluphenazine 2to15 2to10 12 Tab,IM,LAI,oralsolution
33
Haloperidol 2to20 2to10 30 Tab,IM,LAI,oralsolution
20
Loxapine 2080 20 100 CapsuleoralinhalationforuseinhealthcaresettingsasalternativetoIMinjection
OralsolutionandIMinjectionavailableincountriesotherthanUnitedStates
12
Perphenazine 12to24 8to16 24 Tab 912
Pimozide 8to10 1to2 10
4(CYP2D6poormetabolizer)
Tab 55
Thiothixene(tiotixene)
10to20 5to10 30 Capsule 33
Thioridazine 200to600 150 600 Tab 2125
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Trifluoperazine 15to20 4to10 40 Tab 22
Secondgenerationantipsychotics(SGAs)
Aripiprazole 10to15 10to15 30 Tab,ODT,IM,LAI,oralsolution
7594
Asenapine 10to20 10 20 Sublingualtab 24
Clozapine 150to600 2550 900 Tab,ODT,oralsuspension
12
Iloperidone 12to24 2 24
12(CYP2D6poormetabolizerorreceiving2D6inhibitorcotreatment)
Tab 1826
Lurasidone 40to80 40
20(renalorhepaticinsufficiency)
160
80(moderateorsevererenalinsufficiency,moderatehepaticinsufficiency)
40(severehepaticinsufficiency)
Tab 2937(steadystate)
Olanzapine 10to20 5to10 30 Tab,ODT,IM,LAI 3038
Paliperidone 6to12 6 12 ERtab,LAI 23
Quetiapine 150to750(immediaterelease)
400to800(extended
50 750(immediaterelease)
800(extendedrelease)
Tab,ERtab 612
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release)
Risperidone 2to6 1to2 8 Tab,ODT,LAI,oralsolution
20
Ziprasidone 40to160 40to80 200 Capsule,IM 7oral
25IM
Dosesshownaretotaldailydose,oraladministration,formaintenancetreatmentofschizophreniainotherwisehealthyadults.Foradditionalinformation,refertoLexicompindividualdrugmonographsincludedwithUpToDate.
ODT:orallydissolvingtabletTab:tabletERtab:extendedreleasetabletIM:shortactingintramuscularinjectionLAI:longactinginjectable(eg,depot)CYP:cytochromeP450Pgp:membranePglycoproteintransportersUGTglucuronidation:uridine5'diphosphateglucuronyltransferases.*Usualmaximumtotaloraldailydoseformaintenancetreatmentofschizophreniainadultpatientswithoutsignificantcomorbidity.Dosesshownmaynotbethemaximumdoseusedinsomeclinicaltrialsorinexceptionalpatients.Onlypotenttomoderateinhibitoreffectsarelistedinthistable.Foradditionalinformationincludingmoderatetoweakinhibitororinducereffects,andtodeterminespecificdruginteractions,refertoindividualdrugmonographssectionondruginteractionsandtheLexiInteractprogramincludedwithUpToDate.SmokingmaydecreasebloodconcentrationsofantipsychoticsprimarilymetabolizedbyCYP1A2.
Preparedwithdatafrom:1. LexicompOnline.Copyright19782015Lexicomp,Inc.AllRightsReserved.2. WynnGH,etal(eds)ClinicalManualofDrugInteractionPrinciplesforMedicalPracticeAPA
publishing,WashingtonDC.Copyright2009.
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Disclosures:StephenMarder,MDGrant/Research/ClinicalTrialSupport:Sunovion[Psychosis(Lurasidone)].Consultant/AdvisoryBoards:Otsuka[Psychosis(Aripiprazole,brexpiprazole)]Lundbeck[Psychosis(Aripiprazole,brexpiprazole]Pfizer[Psychosis(Ziprasidone)].MichaelDavis,MD,PhDNothingtodisclose.MurrayBStein,MD,MPHGrant/Research/ClinicalTrialSupport:Janssen[socialanxietydisorder].Consultant/AdvisoryBoards:Janssen[anxietyandtraumaticstress]Tonix[anxietyandtraumaticstress]Pfizer[anxietyandtraumaticstress].RichardHermann,MDNothingtodisclose.Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy
Disclosures