Otto Lesch

Comparison of acamprosate and placebo in long-term treatment of alcohol dependence

BACKGROUND About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. METHODS In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. FINDINGS Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. INTERPRETATION Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.

Dopamine and alcohol relapse: D1 and D2 antagonists increase relapse rates in animal studies and in clinical trials.

A considerable number of animal studies on the effects of dopaminergic agents on alcohol intake behavior have been performed. Acute alcohol administration in rats induces dopamine release in the caudate nucleus and in the nucleus accumbens, an effect related among others to reinforcement. It has been repeatedly suggested that D1 and D2 receptor activation mediates reward. As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blind multicenter clinical trial, comparing the D1, D2, D3 antagonist flupenthixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation possible. It could be shown in which patients flupenthixol administration was followed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo.

Prevalence and course of psychiatric disorders among nursing home admissions

Abstract Several studies have shown that psychiatric disorders are common in nursing homes, but information on the course of psychiatric morbidity shortly after admission is still lacking. Therefore, we interviewed 262 residents of Austrian nursing homes within 2 weeks following admission, and a second time after 6 months. Using the Clinical Interview Schedule and its case criteria, prevalence was 76.3% at admission, and 69.9% 6 months later. In the intervening period, the mortality rate was markedly higher among psychiatric cases, and the incidence of new psychiatric cases (5.9%) was slightly lower than the rate of remission (8.6%). At both assessments, organic mental illness was the most frequent diagnosis. Nursing home residents suffering from psychiatric disorders were treated predominantly by general practitioners applying a psychotropic drug regimen.

World Health Organization/International Society for Biomedical Research on Alcoholism study on state and trait markers of alcohol use and dependence: Back to the future

This article summarizes content proceedings of a symposium held at the 2004 International Society for Biomedical Research on Alcoholism Congress in Mannheim, Germany. The chairs were Boris Tabakoff and Friedrich M. Wurst. The presentations were (1) Genetic associations with alcoholism and affective disorders, by Paula Hoffman; (2) Proteomic analysis of blood constituents in alcoholism, by Boris Tabakoff; (3) Contrasts between the responses of GGT and CDT to high alcohol intake, and a test of their combined use, by John Whitfield; (4) Direct ethanol metabolites such as ethyl glucuronide, fatty acid ethyl esters, phosphatidylethanol and ethyl sulfate: a new line of sensitive and specific biomarkers, by Friedrich Martin Wurst; and (5) Genetic studies of alcoholism subtypes in a Han Taiwanese population, by Ru-Band Lu.

Psychiatric disorders in gynaecological, surgical and medical departments of general hospitals in an urban and a rural area of Austria.

A total of 728 patients admitted to the medical, gynaecological and surgical departments of one urban and one rural general hospital in Austria were investigated for psychiatric morbidity. Using the Clinical Interview Schedule and its case criteria, the prevalence of psychiatric morbidity was found to be highest in medical departments (38.2%), followed by surgical departments (32.5%), and lowest in gynaecological departments (20.7%). Among medical and surgical patients, dementia and substance abuse disorders were the most frequent psychiatric categories, while in gynaecological departments neurotic disorders showed the highest frequency. For the sample as a whole, single status (i.e. unmarried, widowed or divorced), lower social class and rural catchment area of the general hospital predicted a high prevalence of psychiatric morbidity in a logistic regression analysis, while complications of childbirth, pregnancy or the puerperium, and diseases of the skin or the musculoskeletal system showed a negative association with psychiatric illness.

Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patients

Information provided by patients about the amounts of alcohol they drink may often be too subjective and therefore unreliable. Because of the possible serious consequences of interactions between alcohol and medication, reliable laboratory test markers for alcohol consumption are needed. Carbohydrate-deficient transferrin (CDT) is at present the best available objective measure of drinking behavior. During a withdrawal trial, 92 alcohol-dependent patients who had been admitted to a hospital in an ethanol-intoxicated state were monitored over the following 28 days by using the percent carbohydrate-deficient transferrin (%CDT of total transferrin) (%CDT) method. At the time of admission, 63% showed elevated %CDT levels. After a subsequent period of abstinence, a decrease in %CDT levels was apparent in four different groups of patients, whereas in two groups, comprising the greatest number of patients, normal %CDT levels were evident after 14 days of abstinence. In patients whose CDT levels were very high at study initiation, it took at least 21 to 28 days--and sometimes longer--for CDT to decrease to the radioimmunoassay (RIA) %CDT test cutoff point of 2.5. In a further study of 56 male alcohol-dependent patients, we measured liver enzyme concentrations, mean corpuscular volume (MCV), and four CDT variants on the first day of evidence of withdrawal syndrome. We found a significant correlation between results on the Munich Alcoholism Test (MALT) and MCV levels; among gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels; and among all four CDT variants. A cluster analysis yielded three clusters: (1) GGT, AST, and ALT levels; (2) MCV levels and MALT results; and (3) all CDT measurement variants. We conclude that these three clusters measure different detriments to the patient and that all available CDT variants are commensurate.

Exclusion of trisialo-transferrin from carbohydrate-deficient transferrin measurement: advantage in patients with chronic liver disease?

ZusammenfassungHINTERGRUND: Biologische Marker des chron. Alkoholkonsums wie MCV, GGT oder Carbohydrate Deficient transferrin (CDT) sind klinisch hilfreich, jedoch nicht absolut aussagekräftig. Besonders bei Patienten mit bereits etablierter Lebererkrankung wäre ein verlässlicher Marker des chronischen Alkoholkonsums zum Erkennen der zu Grunde liegenden Krankheitsätiologie höchst wünschenswert. Die Messung des CDT wurde durch eine verbesserte ELISA Version, die Asialo-, Monosialo- und Disialo-Transferrin misst, nicht jedoch das Trisialo- Transferrin inkludiert weiterentwickelt und verspricht höhere Sensitivität und Spezifität in der Aufdeckung eines kürzlich entdeckten Alkoholkonsums. ZIEL: Studienziel war es bei Patienten mit Lebererkrankung Sensitivität, Spezifität, positiv und negativ prädiktiven Wert des CDT-TRISIALO (−) mit dem CDT-TRISIALO (+) zu vergleichen. PATIENTEN UND METHODEN: Die Studienpopulation bestand aus 110 konsekutiven Patienten (männlich: n = 80 [72,7 %], weiblich: n = 30 [27,3 %]) mit Lebererkrankung der folgenden ätiologischen Kategorien: chronischer Alkoholkonsum (n = 51 [46,4 %], chronische Virushepatitis (n = 33 [30,0 %], Hämochromatose (n = 4 [3,6 %]), mechanische Cholestase (n = 17 [15,5 %]) und andere Lebererkrankungen (n = 5). 30 Patienten hatten keine Leberzirrhose, bei der Mehrheit (n = 80) fand sich eine Leberzirrhose. ERGEBNISSE: Bei Patienten mit Lebererkrankung hatte der CDT-TRISIALO (−) Test beim publizierten Cut-off Wert von 2,6 % eine Sensitivität von 72,7 % und eine Spezifität von 58,1 % für rezent zurückliegenden Alkoholkonsum. Der positiv prädikitve Wert war 34,0 % und der negativ prädiktive Wert 87,8 %. Der CDT TRISIALO (+) Test erreichte bei einem empfohlenen Cut-off Level von 4,7 % mit 73,3 % und 49,3 % ähnliche Sensitivitäts- und Spezifitätswerte. Positiver und negativer prädiktiver Wert lagen bei 30,9 % bzw. 88,1 % Sowohl CDT-TRSIALO (+) als auch CDT-TRSISIALO (−) korrelierten positiv mit dem Child-Pugh Leberzirrhose Stadium. ZUSAMMENFASSUNG: Der modifizierte Carbohydrate Deficient Transferrin (CDT) Test (CDT-TRISIALO (−)) zeigte in einer Gruppe von Patienten mit Lebererkrankung keinen eindeutigen Vorteil gegenüber dem etablierten CDTTRISIALO (+) Test. In einer Population von Patienten mit Lebererkrankungen kann ein normales Ergebnis des sowohl CDT-TRISIALO (+) als auch des CDT-TRISIALO (−) Tests als Argument für den Ausschluss eines rezenten Alkoholgebrauchs gelten.SummaryBACKGROUND: Biological markers for chronic alcohol consumption like MCV or γGT or carbohydrate deficient transferrin (CDT) are useful, but far from being perfect. In patients with liver disease a reliable marker for chronic alcohol consumption as the underlying etiology is highly needed. Recently, a new ELISA based version of the carbohydrate-deficient-transferrin (CDT-TRISIALO (−)) assay has been developed, which measures asialo-, monosialo- and disialo transferrin, but excludes trisialo- transferrin; that modification suggests higher sensitivity and specificity in detecting recent alcohol consumption in patients. AIMS: The study goal was to evaluate the sensitivity, specificity, positive and negative predicitive value of this new carbohydrate-deficient-transferrin assay (CDT-TRISIALO (−)) in a group of patients with liver disease and to compare the results with that of the established CDT assay (CDT-TRISIALO (+)). PATIENTS AND METHODS: Our study population consisted of 110 consecutive patients (male: n = 80 [72.7 %], female: n = 30 [27.3 %]) with liver disease of the following etiologies: chronic alcohol consumption (n = 51 [46.4 %]; Out of them 30 alcohol abusing patients were assessed by cage = 1 and 21 alcohol dependent patients were assessed by cage = 2, chronic viral hepatitis (n = 33 [30.0 %]) including 25 [22.7 %] patients with chronic hepatitis C infection and 8 [7.3 %] patients with chronic hepatitis B infection), haemochromatosis (n = 4 [3.6 %]), mechanical cholestasis (n = 17 [15.5 %]) and other liver diseases (n = 5 [4.6 %] including autoimmune hepatitis (n = 2) and primary biliary cirrhosis (n = 3)). 27.3 % of our patients (n = 30) had no liver cirrhosis whereas the majority (72.7 %, n = 80) had liver cirrhosis. RESULTS: In our population of liver disease patients the CDT-TRISIALO (−) assay had a sensitivity of 72.7 % and specificity of 58.1 % for recent alcohol consumption at the published cutoff level of 2.6 %. The positive predictive value was 34.0 % and the negative predictive value was 87.8 %. Sensitivity and specificity of the CDT-TRISIALO (+) assay at the recommended cutoff level of 4.7 % were similar, 77.3 % and 49.3 %, respectively. The positive and negative predictive values were 30.9 % and 88.1 %. CDTTRISIALO (+) and CDT-TRISIALO (−) levels increased significantly with higher Child-Pugh stages. CONCLUSION: The newly developed carbohydrate deficient transferrin test (CDT-TRISIALO (−)) is of no advantage as compared to the established assay (CDT-TRISIALO (+)) when used in a patient population with liver disease. In that population, normal CDT-TRISIALO (−) helps to exclude recent alcohol consumption; this results from the high negative predictive value of a normal CDT-TRISIALO (−).

The connection of temperament with ADHD occurrence and persistence into adulthood – An investigation in 18 year old males

BACKGROUND This study intended to determine whether certain traits of temperament are associated with former and current ADHD symptomatology in a non-clinical sample of 18 year old males. METHODS We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a socio-demographic questionnaire, screening for substance abuse, temperament (TEMPS-M), past (WURS) and current (ADHD symptom checklist) ADHD symptomatology. RESULTS We found a correlation of cyclothymic (p<.001), irritable (p<.001) and anxious (p<.05) temperament with occurrence and severity of past and present ADHD symptomatology. No significant correlation has been detected for hyperthymic and depressive temperament. Judged retrospectively, ADHD symptoms were strongly consistent over time. LIMITATIONS The sample consists of men only. These had to be fit enough to be enlisted for military service; men with severe mental or physical disorders were thus excluded. Furthermore, the cross-sectional study design does not allow making conclusions about the temporal relationships between ADHD symptoms and substance misuse. CONCLUSIONS These results indicate that a temperament based approach towards those affected by ADHD might be useful. Subtyping ADHD by integrating temperament profiles in diagnosis and treatment of the disorder could help explain some of the heterogeneity of the disease.