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酒精使用障碍的药物治疗进展MedicationforAlcoholUseDisorders交流提纲概述酒精使用障碍（alcoholusedisorder，AUD）酒精依赖酒精戒断反应酒精所致精神病酒精所致人格改变酒精所致智能障碍Theassociationbet

weenalcoholuseandpsychosiswasdocumentedasearlyas1847byMarcel.Hewascreditedfordifferentiatingthedisorderfromdeliriumtremens(Johansson1

961).Kraepelin(1913)andotherauthorsalsoreportedadistinctpsychoticsyndromeassociatedwithalcoholismthatdifferedfromdeliriumtremens(alcoholwithdrawalw

ithdelirium),Wernicke’sencephalopathy,Korsakoff’spsychosisandalcohol-induceddementia(Glass1989a).Psychoticmanifestationsmay

alsooccurinothergeneralmedicalorneurologicaldisordersassociatedwithalcoholdependence(GreenbergandLee2001).Earlydescri

ptionsofadistinctpsychoticsyndromeassociatedwithexcessivealcoholusewerebasedoncase-studiesandclinicalobserv

ation.Bleuler(1916)termedtheconditionalcoholichallucinosis.Follow-upstudiesonpatientgroupsappearedfromar

oundthe1950’sanddescribedthefeaturesofwhatiscurrentlyknownas:Alcohol-inducedPsychoticDisorder(AIPD)(APA,DSM-IV-TR2000;DSM-5,2013),orPsycho

ticDisorderduetotheuseofAlcohol(WHOICD-101993).EssentiallytheDSMcriteriarequire:(A)thepresenceofprominenthallucinationsordelus

ions,(B)evidencefromthehistory,physicalexaminationorlaboratoryfindingsthatthesymptomsdevelopedwithinorduringamonthofalcoholintoxi

cationorwithdrawal.Thesymptomsare(C)notbetteraccountedforbyapsychoticdisorderthatisnotsubstance-induced(e.g.symptomsprecedesubsta

nceuse)and(D)donotexclusivelyoccurduringthecourseofadelirium.DSM5stipulatesthattheperiodofonsetshouldbe“duringorso

on”afterintoxicationorwithdrawalofalcoholandthatthedisturbanceshouldcauseclinicalsignificantdistressorimpairment.Initialstud

iesongroupsofpatientsdidnotcomparepatientswithotherdiagnosticgroups(Benedetti1952;Burton-Bradley1958;V

ictorandHope1958).Conclusionswerebasedonclinicalobservationsandfollow-upstudiesovervariableperiodsoftime.Fromthe1960’sstudiesa

doptedamoresystematicresearchapproach(Glass1989a).EpidemiologyWhereasthelifetimeriskforalcoholdependenceis10–15%(males)and3–5%(female

s)(Schuckit2005),only2–3%ofsuchpatientshadpsychoticsymptoms(VictorandAdams1953).However,thesefiguresdidnotexcludep

atientsexperiencingpsychoticsymptomsassociatedwithalcoholwithdrawaldelirium.ItisestimatedthatAIPDpatientsrepresentaminority(33.1%

)ofthegroupofpatientsexperiencingpsychoticsymptomsassociatedwithalcoholdependence(therestbeingmostlyassociatedwi

thalcoholwithdrawaldelirium)(Soykaetal.1988).TheprevalenceofAIPDinalcoholdependentpatientsvariedbetween0.4%and0.7%(inpatients,Germany)(Soyk

a2008a),4%(inpatients,lifetime,Finland)(Peräläetal.2010)and12.36%(Nepal)(Sedain2013).Alifetimeprevalenceof0.41%wasreportedinthe

generalpopulation(Peräläetal.2010).TheGermanstudyexcludedpatientswithothersubstanceabuse,whilsttheFinnishstudyincludedcomorbidlifeti

mesubstanceuse(20%)andotherpsychiatricdisorders(76%).Alcohol-withdrawaldeliriumwasincludedinthealcohol-inducedps

ychoticsyndrome(AIPS)groupand13%ofAIPDpatientsdevelopedaprimarypsychosis.OverestimationofAIPDprevalencemaythereforebepossibleinthe

Finnishstudy,asthesecomorbiddisordersmayalsobeassociatedwithpsychoticfeatures.UnderreportingofAIPDishoweveralso

possiblebecausesomepatientsmayreceiveotherdiagnoseseg.“dualdiagnosis”,alcohol-withdrawaldeliriumetc.ormaynotseektreatmentbecauseoffavo

urableoutcome(Soyka2008a;Peräläetal.2010;KumarandBankole2010).AIPSwasassociatedwithahighmortalityrate(37%over8years)(Peräläetal.2010),and“AIPD

”(includingpatientswithdeliriumtremens)wasalsoidentifiedasariskfactorforprematuredeath(Mattissonetal.2011).Nosignificantdemographicdiffere

nces(age,education,maritalstatusandemployment)werefoundbetweenmalealcoholicpatientswithandwithoutahistoryofpsychosis(Tsuangetal.1994).Theag

eofonsetofalcoholismreportedinAIPDvariedbetween21.4(Jordaanetal.2009),and29.1years(Tsuangetal.1994)withthelatterstudyshowingasigni

ficantlyyoungerageofonsetofalcoholismforAIPDpatientsthantheirnon-psychoticmalecounterparts.Themeanageofo

nsetofpsychosiswassignificantlylaterinAIPD(36.2and37.4years)comparedtoschizophrenia(24.8and32.8year

s)(Jordaanetal.2009andSoyka1990).ThesexratiosinpatientswithAIPDandalcohol-withdrawaldeliriumweresimilar(male/female:3.64–3.68:1respectively)(Soy

kaetal.1988).Historiesofhigher(Tsuangetal.1994)andlower(Jordaanetal.2009)levelsofalcoholconsumptioninAIPDcom

paredtouncomplicatedalcoholdependentpatientswerereportedinstudieswithvaryingmethodologies.Higherratesof

otherdruguseinAIPDcomparedtouncomplicatedalcoholdependencewerealsoreported(Tsuangetal.1994).ClinicalfeaturesAIPD

ischaracterizedbyacuteonsetofauditoryhallucinations(Benedetti1952;VictorandHope1958;Johansson1961)andoftenpersecutorydelusions,

inclearconsciousness(Seitz1951:VictorandHope1958;Soykaetal.1988;Soyka1990)andtheabsenceofthoughtprocessdisorder(Burton-Bradley1958;Scott

etal.1969;Cutting1978;Surawicz1980;Glass1989a,b)inindividualswithheavyalcoholconsumptionThehallucinationsarecharacteristicallyintheformofderogat

oryvoices(Glass1989a;Soyka1990).While10%ofpatientshavesymptomssuggestiveofdeliriumintheacutephase(Benedetti1952),th

ediagnosisofAIPDcanonlybemadeifpsychoticsymptomspersistinaclearsensorium(Soykaetal.1988).Insomnia,anxiety,anddepression(includingsuicidality

)aresymptomaticofalcohol-usedisorders(Schuckit2009).SimilarsymptomsweredocumentedinearlydescriptionsofAI

PD(Bleuler1916;Glass1989a).Comparedwithalcoholdependence,morepatientswithAIPDhadhistoriesofdepression(Tsuangetal.1994),andanxietysym

ptomsmaybeariskfactorforsuicidalityinAIPD(Jordaanetal.2009).Controversialissuesrelatingtothediagnosis

Controversyregardingthenosologicalstatusofthedisorderhascharacterizedtheliteratureforseveralyears(Glass1989a).AIPDneedstobedist

inguishedfromalcohol-withdrawaldelirium(Soykaetal.1988;Grossetal.1968),schizophrenia(Glass1989a;Soyka1990)and

psychosesassociatedwithgeneralmedicalconditionssuchasepilepsy(Slateretal.1963;Robertsetal.1990;Nicolsonetal.2006)andheadinjuries(DavidandP

rince2005).OtherearlierdescriptionsandexplanationsforAIPDsuggestedanassociationwithbipolardisorder(Schneider1928),depressionwithp

aranoidfeatures(SuwakiandIshino1976)andanassociationwithconcurrentpersonalitytraits(MayandEbaugh1953).Moreoverothersquestioned

theassociationwithalcoholsuggestingthatthedisordercouldoccurintheabsenceofalcoholism(HendersonandGillespie1936).Associationwi

thalcoholwithdrawaldelirium“deliriumtremens”Alcoholwithdrawaldelirium(“deliriumtremens”)mayexhibit

featuressimilartoAIPD,suggestingacloserelationshipbetweenthetwodisorders.Earlyreportsnotedthatthecourseofdeliriumtremenswasshorter(K

raepelin1913;BowmanandJellinek1941)andthehallucinationsmorelikelyvisualthanauditorycomparedtoAIPD(K

raepelin1913).Itwasalsoobservedthatpatientswithalcoholhallucinosiswereusuallycorrectlyorientatedwithintactattentionandfreeofpsychomotoragitati

on(BowmanandJellinek1941).ComparedwithAIPD,patientswithdeliriumtremenswereolder,hadlongeralcoholabusehisto

ries,seemedbetterequippedsociallyandintellectuallyandhadsignificantlyfewerheadinjuriesthanthehallucinosisgroup(Johansson1961).Anotherstu

dyreportednodifferencesinthemarital,occupationalandsocialstatusamongstpatientswithalcoholichallucinosis,chronicalcoholismwithoutpsycho

sisanddeliriumtremens.Itwasalsonotedthatsomepatientswithalcoholhallucinosispresentedwithdeliriousfeatures(Scott1967

).InaseriesofpublicationsGrossetal.(1968,1970,1972a,b)challengedtheimportanceofaclearsensoriumandproposedaspectrum

ofhallucinatorystateswhichallowedformildcloudingofconsciousnessinalcoholichallucinosis.Thesestudiescom

paredtheonset,clinicalpresentation,neuroimagingfindings,treatmentresponseandclinicalcourseinpatientswith

AIPDwiththatofotherdiagnosticcategoriesincludingalcohol-withdrawaldelirium(deliriumtremens),schizophrenia,alcoholdep

endenceandhealthyvolunteers(Johansson1961;Scott1967;Scottetal.1969;Cutting1978;Soykaetal.1988,2012;S

oyka1990;Tsuangetal.1994;AliyevandAliyev2005,2008;Jordaanetal.2009,2010,2012;andPeräläetal.2010.Epidemiology