1. Club Médical Interhospitalier du Hainaut Symposium 2002 « L utilisation clinique du CAMPRAL » Prof. I. Pelc CHU Brugmann - ULB Bruxelles - Belgique

2. MENTAL HEALTH CHARACTERISTICS bio psycho social aspects

3. ACAMPROSATE Acetyl homotaurinate de calcium CH 3 -CO-NH-CH 2 -CH 2 -CH 2 -SO 3 Ca

4. CAMPRAL ® : A MAJOR ADVANCE IN THE TREATMENT OF ALCOHOL DEPENDENCE The first drug specifically developed to work at a neurobiological level in the mechanisms of alcohol dependence A non-aversive, CNS-acting agent Offers positive help in maintaining abstinence after alcohol withdrawal when used in conjunction with psychotherapy and social support

5. Campral ® : A NOVEL ACTION IN ALCOHOL DEPENDENCE NORMAL CHRONIC ALCOHOLISM BALANCE WITHDRAWALCRAVING HYPER EXCITATION BALANCE Inh Exc Inh Exc BARAlc + Exc BRAIN + BAR Alc Inh Exc BRAIN + Inh Exc BRAIN + (learned association) InhExc Campral® + CRAVING BRAIN (learned association)

6. META-ANALYSIS Method of Hedges & Olkin, 1985 uIncluded 15 randomized placebo-controlled, double- blind studies l performed in 11 European countries l involved over 4,400 alcohol-dependent outpatients uConfirmed the significant effect of acamprosate versus placebo on abstinence parameters uSupports the generalizability of acamprosate data

7. STUDY SIZE

8. CUMULATIVE ABSTINENCE DURATION PROPORTION * * *p < 0.05 * * * * * * * * *

9. ACAMPROSATE EUROPEAN DOUBLE- BLIND, PLACEBO-CONTROLLED TRIALS Days to First Drink

10. ACAMPROSATE EUROPEAN DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS Rate of Total Abstinence (%) Overall Mean %: Acamprosate = 35.7% Placebo = 21.9% D = 13.8%

11. * * * * * *: p<0,001 N = 3,338 N = 2,876 N = 958 N = 2,262 N = 866 N = 1,679 % Days ABSTINENCE RATES FOR PATIENTS WHO REMAINED IN THE TRIALS Percentage of patients abstinent (treatment duration 3-12 months)

12. 0 10 20 30 40 50 60 70 80 90 100 Acamprosate Placebo Continuous abstinence: time to first drink % Patients Treatment PeriodFollow-up Period Never had a drink FOLLOW-UP PERIOD (Sass et al.) 60 0120180240300360420480540660600720

13. EFFECT OF CAMPRAL ON ABSTINENCE RATE, CUMULATIVE ABSTINENCE DURATION, COMPLIANCE TO TREATMENT AND CLINICAL GLOBAL IMPRESSION Results after 180 treatment days Pelc I BELGIUM * * * ** * p<0.05 ** p<0.005 Abstinence rateCADComplianceCGI Days % Patients

14. Cumulative Abstinence Duration in days by intervention type (per protocol) THERE IS NO DIFFERENCE IN CAD BETWEEN DIFFERENT TYPES OF PSYCHOTHERAPY IN PATIENTS ON Campral ®

15. DRINKING HABITS - Self-rating Scale (1) I use to drink: 1. When I meet someone 2. When I have some trouble, to forget them 3. Out of habit 4. For the taste 5. For the taste which became a habit 6. It's a family habit 7. To pep up 8. In the company of my spouse 9. Because I like to drink 10. When I feel lonely 11. To raise my morale 12. To avoid trembling the day after a bout of heavy drinking 13. For professional reasons 14. When I feel abandoned Each item is rated as: 0 = never1 = seldom 2 = sometimes3 = frequently according to the global situation during the last 6 months

16. DRINKING HABITS - Self-rating Scale (2) I use to drink: 15. When I have problems which I can't tolerate 16. With a meal 17. When I find myself with a group of drinkers 18. To feel better 19. Before doing something 20. To kill time 21. In the evening to relax 22. To pick me up 23. When I am offered a drink 24. When I feel isolated 25. To be in a good mood when I am with other people 26. When I am bored 27. When I am busy with something 28. When I feel tense, anxious 29. Before meeting someone Each item is rated as: 0 = never1 = seldom 2 = sometimes3 = frequently according to the global situation during the last 6 months

17. DRINKING HABITS - Self-rating Scale (3) I use to drink: 30. When I feel down 31. When I am in a particular surrounding 32. I enjoy drinking 33. To show that I can drink as much or more than anyone 34. To be less anxious, the day after a bout heavy drinking 35. When I am influenced by others to drink 36. When I have to do something unusual 37. To be different from my everyday self 38. Before speaking to certain persons 39. To avoid feeling lousy, the day after a bout of heavy drinking 40. As an escape, to avoid reality 41. To feel more selfassured in certain situations 42. To isolate myself 43. When I feel tired, exhausted 44. After the first drink I can't stop 45. To help me fall asleep at night Each item is rated as: 0 = never1 = seldom 2 = sometimes3 = frequently according to the global situation during the last 6 months

18. MODES OF DRINKING: ALCOHOLISM 1.SOCIAL: in a social setting 2.HABIT: from habit, for the taste 3.STRESS: to escape psychological difficulties 4.PHYSICAL DEPENDENCE: to avoid withdrawal symptoms 5.STIMULUS: as a stimulus for activity, for assertiveness Each mode is rating on a 4 level scale, validated for time and interrater reliability: 0 = never2 = sometimes 1 = seldom3 = frequently

19. CONCLUSIONS CAD values in the NEAT were similar to those in randomised controlled studies Acamprosate increases QoL in enhancing abstinence. Acamprosate Treatment Outcomes Acamprosate AbstinenceQOL

20. Role of Social Support - Brief Intervention and Motivational contact on the efficacy of Acamprosate during the follow-up of detoxified alcoholic patients Pr I. PELC and coll University Hospital Brugmann Université Libre de Bruxelles BELGIUM CAPRISO STUDY

21. Efficacy Variables u Cumulative abstinence duration (CAD) in per cent u Clinical Global Impression u Medication compliance CAPRISO STUDY

22. Cumulative abstinence days (%) p < 0.23 CAPRISO STUDY

23. Influence of baseline variables on CAD % Contd p = 0.008 (interaction test) Attendance to Self Help Group CAPRISO STUDY

24. Structural modelling representation of regression analysis on CAD Education Marital status F.U. Female SHG + CAD 0.12 0.19 0.29 -0.24 -0.22 Regression analysis: R 2 =.49 CAPRISO STUDY

25. Rate of Complete Abstinence throughout a 6 month Period Evaluation after Detoxification CAPRISO STUDY Randomized Placebo-controlled Study * Randomized Psycho-social follow-up Study ** N = 104N = 100 * Acamprosate in the treatment of alcohol dependence: a 6 months post- detoxification study - I. Pelc and coll, 1992 * * Capriso Study I. Pelc and coll, 2001 Placebo Acamprosate 4% 24% Acamprosate No Fu Fu 14% 32%