Clinical Manifestations, Differential Diagnosis, And Initial Management of Psychosis in Adults

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.



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.



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



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".)



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



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



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".)



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.

Topic17193Version5.0


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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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SciHub



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]



DurnCE,AzermaiM,VanderSticheleRH.Systematicreviewofanticholinergicriskscalesinolderadults.EurJClinPharmacol201369:1485.




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



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



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.




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

Documents

Clinical Manifestations, Differential Diagnosis, And Initial Management of Psychosis in Adults