酒精使用障碍的药物治疗医学

酒精使用障碍的药物治疗进展 Medication for Alcohol Use Disorders 交流提纲 概述 酒精使用障碍（ alcohol use disorder， 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 The association between alcohol use and psychosis was documented as early as 1847 by Marcel. He was credited for differentiating the disorder from delirium tremens (Johansson 1961). Kraepelin (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). Psychotic manifestations may also occur in other general medical or neurological disorders associated with alcohol dependence(Greenberg and Lee 2001). Early descriptions of a distinct psychotic syndrome associated with excessive alcohol use were based on case-studies and clinical observation. Bleuler (1916) termed the condition alcoholic hallucinosis. Follow-up studies on patient groupsappeared from around the 1950s and described the features of what is currently known as: Alcohol-induced Psychotic Disorder (AIPD) (APA, DSM-IV-TR 2000; DSM-5, 2013), or Psychotic Disorder due to the use of Alcohol (WHO ICD-10 1993). Essentially the DSM criteria require: (A) the presence of prominent hallucinations or delusions, (B) evidence from the history, physical examination or laboratory findings that the symptoms developed within or during a month of alcohol intoxication or withdrawal. The symptoms are (C) not better accounted for by 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. DSM 5 stipulates that the period of onset should be “during or soon” after intoxication or withdrawal of alcohol and that the disturbance should cause clinical significant distress or impairment. Initial studies on groups of patients did not compare patients with other diagnostic groups (Benedetti 1952; Burton- Bradley 1958; Victor and Hope 1958). Conclusions were based on clinical observations and follow-up studies over variable periods of time. From the 1960s studies adopted a more systematic research approach (Glass 1989a). Epidemiology Whereas the lifetime risk for alcohol dependence is 1015 % (males) and 35 % (females) (Schuckit 2005), only 23 % of such patients had psychotic symptoms (Victor and Adams 1953). However, these figures did not exclude patients experiencing psychotic symptoms associated with alcoholwithdrawal delirium. It is estimated that AIPD patients represent a minority (33.1 %) of the group of patients experiencing psychotic symptoms associated with alcohol dependence (the rest being mostly associated with alcohol withdrawal delirium) (Soyka et al. 1988). The prevalence of AIPD in alcohol dependent patients varied between 0.4 % and 0.7 % (inpatients, Germany) (Soyka 2008a), 4 % (inpatients, lifetime, Finland) (Perl et al. 2010) and 12.36 % (Nepal) (Sedain 2013). A lifetime prevalence of 0.41 % was reported in the general population (Perl et al. 2010). The German study excluded patients with other substance abuse, whilst the Finnish study included comorbid lifetime substance use (20 %) and other psychiatric disorders (76 %). Alcohol-withdrawal delirium was included in the alcohol-induced psychotic syndrome (AIPS) group and 13 % of AIPD patients developed a primary psychosis. Overestimation of AIPD prevalence may therefore be possible in the Finnish study, as these comorbid disorders may also be associated with psychotic features. Underreporting of AIPD is however also possible because some patients may receive other diagnoses eg. “dual diagnosis”, alcohol-withdrawal delirium etc. or may not seek treatment because of favourable outcome (Soyka 2008a; Perl et al. 2010; Kumar and Bankole 2010). AIPS was associated with a high mortality rate (37 % over 8 years) (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). No significant demographic differences (age, education, marital status and employment) were found between male alcoholic patients with and without a history of psychosis (Tsuang et al. 1994). The age of onset of alcoholism reported in AIPD varied between 21.4 (Jordaan et al. 2009), and 29.1 years (Tsuang et al. 1994) with the latter study showing a significantly younger age of onset of alcoholism for AIPD patients than their non-psychotic male counterparts. The mean age of onset of psychosis was significantly later in AIPD (36.2 and 37.4 years) compared to schizophrenia (24.8 and 32.8 years) (Jordaan et al. 2009 and Soyka 1990). The sex ratios in patients with AIPD and alcohol- withdrawal delirium were similar (male/female: 3.643.68:1 respectively) (Soyka et al. 1988). Histories of higher (Tsuang et al. 1994) and lower (Jordaan et al. 2009) levels of alcohol consumption in AIPD compared to uncomplicated alcohol dependent patients were reported in studies with varying methodologies. Higher rates of other drug use in AIPD compared to uncomplicated alcohol dependence were also reported (Tsuang et al. 1994). Clinical features AIPD is characterized by acute onset of auditory hallucinations (Benedetti 1952; Victor and Hope 1958; Johansson 1961) and often persecutory delusions, in clear consciousness (Seitz 1951: Victor and Hope 1958; Soyka et al. 1988; Soyka 1990) and the absence of thought process disorder (Burton- Bradley 1958; Scott et al. 1969; Cutting 1978; Surawicz 1980; Glass 1989a, b) in individuals with heavy alcohol consumption The hallucinations are characteristically in the form of derogatory voices (Glass 1989a; Soyka 1990). While 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). Insomnia, anxiety, and depression (including suicidality) are symptomatic of alcohol-use disorders (Schuckit 2009). Similar symptoms were documented in early descriptions of AIPD (Bleuler 1916; Glass 1989a). Compared 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). Controversial issues relating to the diagnosis Controversy regarding the nosological status of the disorder has characterized the literature for several years (Glass 1989a). AIPD 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). Other 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). Moreover others questioned the association with alcohol suggesting that the disorder could occur in the absence of alcoholism (Henderson and Gillespie 1936). Association with alcohol withdrawal delirium “delirium tremens” Alcohol withdrawal delirium (“delirium tremens”) may exhibit features similar to AIPD, suggesting a close relationship between the two disorders. Early reports noted that the course of delirium tremens was shorter (Kraepelin 1913; Bowman and Jellinek 1941) and the hallucinations more likely visual than auditory compared to AIPD (Kraepelin 1913). It was also observed that patients with alcohol hallucinosis were usually correctly orientated with intact attention and free of psychomotor agitation (Bowman and Jellinek 1941). Compared with AIPD, patients with delirium tremens were older, had longer alcohol abuse histories, seemed better equipped socially and intellectually and had significantly fewer head injuries than the hallucinosis group (Johansson 1961). Another study reported no differences in the marital, occupational and social status amongst patients with alcoholic hallucinosis, chronic