酒精使用障碍的药物治疗课件

酒精使用障碍的药物治疗进展Medication for Alcohol Use Disorders酒精使用障碍的药物治疗进展Medication for Al1交流提纲交流提纲2概述o酒精使用障碍（alcohol use disorder，AUD）o酒精依赖o酒精戒断反应o酒精所致精神病o酒精所致人格改变o酒精所致智能障碍概述酒精使用障碍（alcohol use disorder，3oThe association between alcohol use and psychosis was documentedas early as 1847 by Marcel.oHe was credited for differentiating the disorder from delirium tremens (Johansson 1961).The association between alcoho4oKraepelin(1913)and other authors also reported a distinct psychotic syndrome associated with alcoholism that differed from delirium tremens(alcohol withdrawal with delirium),Wernickes encephalopathy,Korsakoffs psychosis and alcohol-induced dementia(Glass 1989a).Kraepelin(1913)and other aut5oPsychotic manifestations may also occur in other general medical or neurological disorders associated with alcohol dependence(Greenberg and Lee 2001).Psychotic manifestations may a6oEarly descriptions of a distinct psychotic syndrome associated with excessive alcohol use were based on case-studies and clinical observation.oBleuler(1916)termed the condition alcoholic hallucinosis.Early descriptions of a distin7oFollow-up studies on patient groupsappeared from around the 1950s and described the features of what is currently known as:oAlcohol-induced Psychotic Disorder(AIPD)(APA,DSM-IV-TR 2000;DSM-5,2013),oor Psychotic Disorder due to the use of Alcohol(WHO ICD-10 1993).Follow-up studies on patient g8oEssentially the DSM criteria require:o(A)the presence of prominent hallucinations or delusions,o(B)evidence from the history,physical examination or laboratory findings that the symptoms developed within or during a month of alcohol intoxication or withdrawal.oThe symptoms are(C)not better accounted foroby a psychotic disorder that is not substance-induced(e.g.symptoms precede substance use)and(D)do not exclusively occur during the course of a delirium.Essentially the DSM criteria r9oDSM 5 stipulates thatothe period of onset should be“during or soon”after intoxicationoor withdrawal of alcohol and that the disturbance shouldocause clinical significant distress or impairment.DSM 5 stipulates that10oInitial studies on groups of patients did not compare patients with other diagnostic groups(Benedetti 1952;Burton-oBradley 1958;Victor and Hope 1958).oConclusions were based on clinical observations and follow-up studies overovariable periods of time.oFrom the 1960s studies adopted a more systematic research approach(Glass 1989a).Initial studies on groups of p11EpidemiologyoWhereas the lifetime risk for alcohol dependence is 1015%o(males)and 35%(females)(Schuckit 2005),only 23%ofosuch patients had psychotic symptoms(Victor and Adamso1953).EpidemiologyWhereas the lifeti12oHowever,these figures did not exclude patientsoexperiencing psychotic symptoms associated with alcoholwithdrawalodelirium.It is estimated that AIPD patients representoa minority(33.1%)of the group of patients experiencingopsychotic symptoms associated with alcohol dependence(theorest being mostly associated with alcohol withdrawal delirium)o(Soyka et al.1988).However,these figures did not13oThe prevalence of AIPD in alcoholodependent patients varied between 0.4%and 0.7%(inpatients,oGermany)(Soyka 2008a),4%(inpatients,lifetime,oFinland)(Perl et al.2010)and 12.36%(Nepal)(Sedaino2013).A lifetime prevalence of 0.41%was reported in theogeneral population(Perl et al.2010).The prevalence of AIPD in alco14oThe German studyoexcluded patients with other substance abuse,whilst theoFinnish study included comorbid lifetime substance useo(20%)and other psychiatric disorders(76%).The German study15oAlcohol-withdrawal delirium was included in the alcohol-inducedopsychotic syndrome(AIPS)group and 13%of AIPD patientsodeveloped a primary psychosis.Alcohol-withdrawal delirium wa16oOverestimation of AIPDoprevalence may therefore be possible in the Finnish study,asothese comorbid disorders may also be associated with psychoticofeatures.Overestimation of AIPD17oUnderreporting of AIPD is however alsoopossible because some patients may receive other diagnosesoeg.“dual diagnosis”,alcohol-withdrawal delirium etc.or mayonot seek treatment because of favourable outcome(Soykao2008a;Perl et al.2010;Kumar and Bankole 2010).Underreporting of AIPD is howe18oAIPS was associated with a high mortality rate(37%over 8 years)o(Perl et al.2010),and“AIPD”(including patients with delirium tremens)was also identified as a risk factor for premature death(Mattisson et al.2011).AIPS was associated with a hig19oNo significant demographic differences(age,education,omarital status and employment)were found between maleoalcoholic patients with and without a history of psychosiso(Tsuang et al.1994).No significant demographic dif20oThe age of onset of alcoholism reportedoin AIPD varied between 21.4(Jordaan et al.2009),ando29.1 years(Tsuang et al.1994)with the latter study showingoa significantly younger age of onset of alcoholism for AIPDopatients than their non-psychotic male counterparts.The meanoage of onset of psychosis was significantly later in AIPD(36.2oand 37.4 years)compared to schizophrenia(24.8 ando32.8 years)(Jordaan et al.2009 and Soyka 1990).The age of onset of alcoholism21oThe sexoratios in patients with AIPD and alcohol-withdrawal deliriumowere similar(male/female:3.643.68:1 respectively)(Soykaoet al.1988).The sex22oHistories of higher(Tsuang et al.1994)and lower(Jordaanoet al.2009)levels of alcohol consumption in AIPD comparedoto uncomplicated alcohol dependent patients were reported inostudies with varying methodologies.Higher rates of otherodrug use in AIPD compared to uncomplicated alcohol dependenceowere also reported(Tsuang et al.1994).Histories of higher(Tsuang et23Clinical featuresoAIPD is characterized by acute onset of auditory hallucinationso(Benedetti 1952;Victor and Hope 1958;Johanssono1961)and often persecutory delusions,in clear consciousnesso(Seitz 1951:Victor and Hope 1958;Soyka et al.1988;Soykao1990)and the absence of thought process disorder(Burton-oBradley 1958;Scott et al.1969;Cutting 1978;Surawicz 1980;oGlass 1989a,b)in individuals with heavy alcohol consumptionClinical featuresAIPD is chara24oThe hallucinations are characteristically in the form of derogatory voices(Glass 1989a;Soyka 1990).oWhile 10%ofpatients have symptoms suggestive of delirium in the acute phase(Benedetti 1952),the diagnosis of AIPD can only be made if psychotic symptoms persist in a clear sensorium(Soyka et al.1988).The hallucinations are charact25oInsomnia,anxiety,and depression(including suicidality)are symptomatic of alcohol-use disorders(Schuckit 2009).oSimilar symptoms were documented in early descriptions of AIPD(Bleuler 1916;Glass 1989a).oCompared with alcohol dependence,more patients with AIPD had histories of depression(Tsuang et al.1994),and anxiety symptoms may be a risk factor for suicidality in AIPD(Jordaan et al.2009).Insomnia,anxiety,and depress26Controversial issues relating to the diagnosisoControversy regarding the nosological status of the disorder has characterized the literature for several years(Glass 1989a).oAIPD needs to be distinguished from alcohol-withdrawal delirium(Soyka et al.1988;Gross et al.1968),schizophrenia(Glass 1989a;Soyka 1990)and psychoses associated with general medical conditions such as epilepsy(Slater et al.1963;Roberts et al.1990;Nicolson et al.2006)and head injuries(David and Prince 2005).Controversial issues relating 27oOther earlier descriptions and explanations for AIPD suggested an association with bipolar disorder(Schneider 1928),depression with paranoid features(Suwaki and Ishino 1976)and an association with concurrent personality traits(May andEbaugh 1953).oMoreover others questioned the association with alcohol suggesting that the disorder could occur in the absence of alcoholism(Henderson and Gillespie 1936).Other earlier descriptions and28Association with alcohol withdrawal delirium“delirium tremens”oAlcohol withdrawal delirium(“delirium tremens”)may exhibitofeatures similar to AIPD,suggesting a close relationshipobetween the two disorders.Association with alcohol withd29oEarly reports noted that the courseoof delirium tremens was shorter(Kraepelin 1913;Bowmanoand Jellinek 1941)and the hallucinations more likely visualothan auditory compared to AIPD(Kraepelin 1913).Early reports noted that the c30oIt was alsooobserved that patients with alcohol hallucinosis were usuallyocorrectly orientated with intact attention and free of psychomotoroagitation(Bowman and Jellinek 1941).It was also31oCompared withoAIPD,patients with delirium tremens were older,had longeroalcohol abuse histories,seemed better equipped socially andointellectually and had significantly fewer head injuries thanothe hallucinosis group(Johansson 1961).Compared with32oAnother study reported no differences in the marital,occupationaloand social status amongst patients with alcoholicohallucinosis,chronic alcoholism without psychosis and deliriumotremens.Another study reported no diff33oIt was also noted that some patients with alcoholohallucinosis presented with delirious features(Scott 1967).Inoa series of publications Gross et al.(1968,1970,1972a,b)ochallenged the importance of a clear sensorium and proposedoa spectrum of hallucinatory states which allowed for mildoclouding of consciousness in alcoholic hallucinosis.It was also noted that some pa34oTheseostudies compared the onset,clinical presentation,neuroimagingofindings,treatment response and clinical course inopatients with AIPD with that of other diagnostic categoriesoincluding alcohol-withdrawal delirium(delirium tremens),oschizophrenia,alcohol dependence and healthy volunteerso(Johansson 1961;Scott 1967;Scott et al.1969;Cuttingo1978;Soyka et al.1988,2012;Soyka 1990;Tsuang et al.o1994;Aliyev and Aliyev 2005,2008;Jordaan et al.2009,o2010,2012;and Perl et al.2010.oEpidemiologyThese35