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THE STAKE : 10 MIO POTENTIAL CUSTOMERS IN EUROPE Population of Western Europe ± 325 Mio Number of withdrawals/ year (±4%) (±4%) Number of alcohol dependent.

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Presentation on theme: "THE STAKE : 10 MIO POTENTIAL CUSTOMERS IN EUROPE Population of Western Europe ± 325 Mio Number of withdrawals/ year (±4%) (±4%) Number of alcohol dependent."— Presentation transcript:

1 THE STAKE : 10 MIO POTENTIAL CUSTOMERS IN EUROPE Population of Western Europe ± 325 Mio Number of withdrawals/ year (±4%) (±4%) Number of alcohol dependent ± 10 Mio Abstinent at 1 year (±18%) Abstinent at 5 years (±6%)

2 STATES OF CHANGE - REVOLVING DOOR MODEL (Di Clemente et Prochaska, 1982) Précontemplation Contemplation Préparation Action Maintenance Relapse Décision

3 TYPES OF CRAVING: DEFINITIONS n Psychological craving: u Strong desire for drinking alcohol u Strong, almost overpowering urge for alcohol during acute withdrawal u Strong desire or sense of compulsion to take alcohol (ICD- 10) u Persistent desire or unsuccessful efforts to cut down or control alcohol use (DSM-IV) n Physical craving: u Elevated heart rate, u Sweeting, u Nausea, u Anxiety

4 MANY STIMULI PRECEDE THE ARRIVAL OF ALCOHOL INSIDE THE BRAIN BAR Sights and sounds of the environment Smell of alcohol etc. Taste of alcohol

5 Each cue initiates adaptation inside the brain HOW CONDITIONED STIMULI BECOMES CUES FOR RELAPSE? BAR This is our patient, he/she has been detoxified and has turned his/her back on alcohol and all the associated stimuli. Unfortunately, in our alcohol-based society it is impossible to avoid all these stimuli for long.

6 HOW CONDITIONED STIMULI BECOME CUES FOR RELAPSE BAR Any of these stimuli induce adaptation which produces feelings opposite to those of alcohol eg anxiety, dysphoria. These feelings can be self-medicated with alcohol but the decision to do so intensifies all the cues. BAR alcohol In order to balance the increasingly severe "pseudo-withdrawal produced by the conditioned adaptation the patient relapses into heavy drinking

7 PAVLOVIAN CONDITIONING AND THE EFFECTS OF ALCOHOL BAR Associated stimuli As the associated stimuli repeatedly precede the arrival of alcohol in the brain "conditioning" occurs ALCOHOL Unconditioned stimulus BAR Conditioned stimuli BAR Once the stimuli have become conditioned they elicit the response (eg feelings of relaxation) even before the alcohol arrives in the brain Response BAR


9 From: Heather (1995) Source: Institute of Medicine (1990) None Mild Moderate Substantial Severe Brief intervention Primary prevention Specialized treatment ALCOHOL PROBLEMS RELATIONSHIP BETWEEN THE SEVERITY OF ALCOHOL PROBLEMS AND THE TYPE OF INTERVENTION NEEDED

10 Motivational interviewing Cognitive - behaviour theory Relapse prevention Community reinforcement EFFECTIVE PSYCHOLOGICAL TREATMENT FOR DRINKING PROBLEMS

11 % Baseline level Ref: De Witte Progress in Neurobiology. 2000, Campral ® AND GLUTAMATE Time (hr) after withdrawal p < 0.001

12 WITHDRAWAL Motility / Rat / 12h Ref: De Witte P < 0.05

13 ACAMPROSATE ¶No effect on non-alcohol-preferring and non-dependent animals ·Abolishes the alcohol dependence in dependent animals ¸Abolishes the alcohol withdrawal ¹Keeps dependent animals alive during multiple successive withdrawals Ref: De Witte presentation

14 MATERIAL Combined Data Analysis 11 Double blind, placebo controlled multicentre studies 8 European countries alcohol dependent patients Mean Age42.8 years ± 9.3 Sex: female19% Mean MAST score31.8 ± 10.9 Mean CAGE score3.5 ± 0.76

15 METHODOLOGY 1 Data of all 11 trials were reasonably comparable for criteria which included: u demographic variables u clinical histories u the major efficacy outcome criteria Safety data were readily comparable for 9 studies Treatment Duration: 3 months in one trial, 6 months in 5 trials and 12 months in 5 trials Medication free follow-up periods varied from 4 weeks to 12 months Assessment intervals during treatment differed Common data were identified at days 0, 30, 90, 180, 270, 360

16 METHODOLOGY 2 Comparability All placebo controlled trials, performed under naturalistic conditions Two treatment groups (acamprosate and placebo) in 9 trials; three treatment groups (two acamprosate groups at different dosages and one placebo group) in 2 trials. 4-6 tablets per day All patients were started on study medication after the period of acute detoxification: u 10 trials immediately after acute withdrawal therapy, all patients abstinent at start of treatment u 1 trial within 6 weeks of termination of acute withdrawal therapy, 60% patients abstinent

17 METHODOLOGY 3 To follow a CORE PROTOCOL ± adaptations according countries requests Studies carried out in accordance with the EUROPEAN GOOD CLINICAL PRACTICE To use CENTRAL LABORATORY FACILITIES (PRAMA, UKMAS) or to standardise the laboratory values PRIMARY OUTCOME CRITERION: Drinking behaviour 1- Abstinence/Relapse/Missing assessment at each visit 2- Time to first relapse (survival analysis) 3- Cumulative Abstinence Duration (a mathematical sum of all abstinent periods)

18 OUTCOME CRITERIA Number of dry days: cumulative abstinence duration (CAD) If exact data were available: cumulate directly Time to First Relapse = 30 days Cumulative Abstinence Duration = 75 days CAD Relapses Cumulative Abstinence Duration = 60 days CAD Relapses If exact data were not available: consider total period between visits D0 D30D60D90D120D150D180 Visit

19 OUTCOME CRITERIA At each visit: drinking or not? Time to first drink D0D30D60D90D120D150 D180 AARRRAA A = abstinence R = relapse Alcohol consumption (quantity) Assessment visits


21 EUROPEAN TRIALS: RATE OF TOTAL ABSTINENCE (%) 2 way ANOVA - treatment: p<0.001, study: p<0.001, interact: NS

22 RESULTS: ABSTINENT RATE Days Survival analysis %Abstinence rate (no alcohol consumption) It measures: time to first relapse absolute abstinence Comment: this method does not take subsequent abstinent periods into consideration, but is a conservative measure to assess outcome % Mantel Cox: p<0.001

23 RESULTS: PROPORTION OF ATTENDING PATIENTS Differential attrition between treatment groups Comment: drop-out rate in naturalistic trials could be an objective outcome measure of efficacy Days Attendance rate (%) * * **

24 RESULTS: ABSTINENCE RATE PER VISIT Days Abstinence rate (%) * * ** * *: p<0,001

25 SF 36 QoL SCORES BEFORE AND AFTER CAMPRAL TREATMENT Before Treatment After Campral ® Treatment MHMental Health SFSocial Funtioning RERole Emotional VTVitality HTHealth Transition PFPhysical Functioning BPBodily pain RPRole Physical GHGeneral Health Physical Component Mental Component

26 CONCLUSIONS FROM Campral ® CLINICAL STUDIES Double the abstinence rates compared with placebo Used within a programme of psychosocial support, Campral ® can significantly improve abstinence rates following alcohol withdrawal Campral ® is equally effective with a range of psychosocial support strategies

27 RESULTS: ADVERSE EVENTS Adverse events of statistical significance with a frequency of more than 5% were: Gastro-intestinal irritation Sex drive changes Difficulty in falling asleep 15% in the first 30 days, 8% d % in the first 30 days 7% between days 181 and 270 3% more than placebo 3% more than placebo 4-8% more than placebo GOOD SAFETY PROFILE

28 Campral ® : A MAJOR ADVANCE IN THE TREATMENT OF CHRONIC ALCOHOLISM A novel and unique non-aversive therapeutic agent Abstinence rates twice that with placebo achieved when used in conjunction with psycho-social support measures Good tolerability established No significant dependence potential

29 CAD

30 u 248 Patients u 28 weeks Campral treatment for all patients (4-6 tablets / day) u 3 Treatment Groups with different levels of counselling u Manual driven u Session recordings MICADO STUDY (Netherlands) De Wildt et al (submitted for publication)

31 MICADO STUDY (Netherlands) De Wildt et al 3 Treatment Groups a) Campral only: 6 weekly min medical visits. Collect drinking data, evaluate vital signs no reinforcement, motivation, high risk situation discussions. –b) Campral with Minimal Intervention (MI) a plus: 3 x 20 min weekly visits (W 2, 3, 4) –discuss cost benefit drinking –discuss drinking situations –review motivation –c) Campral with Brief Psycho-Social Intervention (PSI) a plus: 7 x 60 min weekly visits (W 2, 3, 4, 5, 6, 7, 8) Increase coping skills (Monti, Abrams et al 89, MATCH-Kadden 92, Schippers 94) significant other, good and bad moments, problem solving, cognitive restructuring

32 MICADO STUDY (Netherlands) De Wildt et al

33 CONCLUSIONS u14 out of 17 studies confirmed that acamprosate reduces relapse in alcohol dependence. uTreatment over 12 months suggests continued abstinence after termination of medication. uAdverse events are rare and minor. uEarly evidence suggests that acamprosate without particular psycho-social support may be as effective as acamprosate combined with minimal or brief intervention. Further investigation is necessary.

34 ACAMPROSATE AND QUALITY OF LIFE HRQoL secondary analysis of the European NEAT Programme Synthesis from 5 countries: Austria, Belgium, Portugal, Switzerland and the United Kingdom F. Poldrugo, Department of Psychiatry, University of Trieste, Italy P. Lehert, Catholic University of Mons, Belgium Main Investigators: C. Ansoms, F. Fisher, W.J. Fuchs, M. Morgan, I. Pelc and A.J. Pires Preto

35 Study design u Primary objectives: –Comparison of the efficacy of acamprosate with or without a –follow-up by a social nurse after detoxification u Study design: –The patients were hospitalized for 3 weeks and randomized to one of the 2 treatment groups Group 1: The patient sees his/her GP whenever necessary. However, the follow-up is monitored by a nurse Group 2: The patient is seen by his/her GP u Treatment duration: –26 weeks CAPRISO STUDY

36 Methods (1) u Prospective evaluation during a 26 weeks follow-up period of alcoholic patients, after detoxification u Two randomized parallel groups with follow-up by a social nurse (F group, N = 50) or without follow-up (NF group, N = 50) u Evaluation visit at week 1, 2, 3, 4, 6, 10, 14, 18, 22, 26 u Outpatient from week 4 u Acamprosate for all patients CAPRISO STUDY

37 Methods (2) u Evaluation of efficacy: For every visit, the patient is considered as abstainer, relapser or missing. Missing = relapser u Outcome criteria: Main endpoint: CAD (sum of complete abstinent days) * Second endpoints: CGI and compliance u Statistical analysis: Anova on ranks Explanatory analysis: GLM on ranks A priori Power: n = 2*50 / =.05 =.2 = 25% 2 - sided CAPRISO STUDY

38 Population (N = 100) - Exclusion Criteria uOther dependencies except nicotine uAn expected longer hospital stay more than 3 weeks for detoxification uKnown renal insufficiency uPrevious treatment with acamprosate uHaving participated in another study in the last 30 days uPregnancy or breast feeding in women of childbearing age uLegal incapacity CAPRISO STUDY

39 Population (N = 100) - Inclusion Criteria uMen and women from 18 to 65 years old uDSM-IV criteria for alcohol dependence uLast alcohol consumption within the previous 7 days uUndergoing an inpatient detoxification planned for 3 weeks uLiving in the region of Brussels uHaving given written informed consent CAPRISO STUDY

40 Baseline data per type of follow up CAPRISO STUDY

41 Population (N = 100) - Demographic Data Age (years) Gender female (%)22 Marital status (%) Education status (%) Family history (%)63 Smoking (%)82 Employement (%) CAPRISO STUDY

42 Initial Severity Living status Smoking habits Drinking pattern Number of previous withdrawal Influence of baseline variables on CAD % Contd No evident effect observed with CAPRISO STUDY

43 Clinical Global Impression 2 : p = CAPRISO STUDY

44 Conclusion 1.Significant differences in outcomes between the 2 treatment conditions showing a strong influence of social nurse intervention during psycho-social follow-up 2.Success rate of the pharmacological active treatment (Acamprosate, I. Pelc, 1992) is positively or negatively influenced by a psycho-social support process 3.Significant influence of Age, Education, Marital status, Family History, Gender and Previous Attendance to SHG on CAD 4.No significant influence of Smoking, Drinking Pattern, Living Status, Number of Previous Detoxification and Initial Severity 5.Providing psycho-social support has to be relevant to patients specific needs CAPRISO STUDY

45 I. PELC, M.D., Ph.D. Collaborators P. Verbanck M.D, Ph. D. O. Le BON M.D.Psychiatrists C. Hanak M.D. J. Tecco M.D. A. VandenborreChief Nurse D. Montag, S. MinetSocial Workers M. Streel, X. NoëlB.Sc. Psychologists C. Houtain, I. BaertSocial Nurse ResearchersUniversité Libre de Bruxelles Clinical Department and Laboratory of Psychological Medecine, Alcohology and Drug Dependence and General Practitioners of the Brussels Region Dr F. DeckersMerck - Lipha - Bruxelles Dr F. LandronMerck - Lipha - Lyon Prof. P. LehertUniversity of Mons (Belgium) and University of Melbourne (Australia) - Statistical Analysis CAPRISO STUDY

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