1. 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

2. 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

3. 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

4. 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

5. ANGER 70 % This person feels anger 1 2 3 4 5 6 7 Not at all Very intensively

6. INTENSITY SCORES AS FUNCTION OF GROUP AND FACIAL EXPRESSION Note. * p<.05; ** p<.01 Kornreich et al. (2001) Journal of Studies on Alcohol Emotional Facial Expressions IntensityscoresIntensityscores

7. COMPARISONS BETWEEN PERFORMANCES ON THE SERIAL AND THE ALPHABETICAL RECALL SCORES ON THE ALPHA-SPAN TEST Effect of group: F 1,58 =43.6, p<.001; Effect of condition: F 1,58 =90.9, p<.001 Interaction between group and condition: F 1,58 =54.6, p<.001 * Post-hoc analysis indicated that ALC performed lower only in alphabetic recall (p<.01) ScoreScore

8. AVERAGE NUMBER OF ERRORS MADE BY ALCOHOLICS AND CONTROLS ON THE HAYLING TEST Note. *** p<.001 PointsofpenaltyPointsofpenalty

9. RELATIONSHIP BETWEEN POSITIVE AND NEGATIVE REINFORCEMENT drug POSITIVE REINFORCEMENT chemical drug reward Glu, GABA, DA/endorphins drug adapt CHRONIC DRUG TOLERANCE neurochemical adaptation Glu RS, GABAA Rs, ? DA/Es drugadapt NEGATIVE REINFORCEMENT exposure of neuronal adaptation early minor signs of withdrawal adaptation WITHDRAWAL SIGNS until adaptation is removed DETOXIFICATION IS RELATIVELY EASY MAJOR THERAPEUTIC PROBLEMS BEGIN HERE

10. CONDITIONING OF REINFORCEMENTS = CRAVING? + CUE D DD Repeated pairing "conditions" associated stimulus ("cue") CUE POSITIVE ASPECTS OF CRAVING Conditioned stimulus (cue) elicits anticipation of drug reward e.g. relaxation, euphoria, excitement + CUE D D D Cue becomes conditioned stimulus for adaptation CUE NEGATIVE ASPECTS OF CRAVING Conditioned stimulus (cue) elicits "pseudo-withdrawal" e.g. anxiety, dysphoria, depression, tremor, etc. A A A A

11. THE MECHANISMS OF ALCOHOL DEPENDENCE Adaptation to alcohol as the basis for the Withdrawal Syndrome Excitation Inhibition Alcohol administration Withdrawal Acute effect Withdrawal syndrome Development of tolerance Littleton JM. Addiction, 1995 Immediate CNS depressant effects of ethanol become limited by neurochemical adaptation Exposure of adaptation causes hyperexcitation

12. 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)

13. EFFECT OF Campral ® ON DISRUPTED NEUROTRANSMISSION Acute alcohol intake Chronic exposure to alcohol Adaptation EAA* * Excitatory Amino Acids Glutamate in particular GABA GABA + EAA - EAA Campral ®

14. 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

15. STUDY SIZE

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

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

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

19. RESULTS: % ABSTAINERS IN PATIENTS ON TREATMENT 5 TRIALS (TREATMENT DURATION: 12 MONTHS) % Days * * * ** *: p<0,001

20. * * * * * 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)

21. 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

22. 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

23. NEW EUROPEAN ALCOHOLISM TREATMENT (NEAT) ACAMPROSATE PROGRAM u Open label, multicenter, multinational (5) u 1 281 alcohol-dependent patients u 6-month study duration u Concurrent group, individual, relapse prevention or brief intervention therapy u Comparisons of acamprosate efficacy across therapy conditions found l significant improvement in all groups in maintaining abstinence and reducing relapse duration l no difference between behavioral therapy groups

24. 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 ®

25. CONCLUSIONS (1) Of all patients included 1. HRQoL in markedly reduced in alcoholic patients 2. The greater deficit is related to mental and social functioning 3. QoL at baseline is influenced by severity of alcoholism, health, employment status, age and gender Of compliant patients 4. Treatment normalised QoL in three months 5. Abstinence and compliance are the best predictor of QoL at study end

26. CONCLUSIONS (2) CAD values in the NEAT were similar to those in randomised controlled studies Acamprosate increases QoL in enhancing abstinence. Acamprosate Abstinence QOL Acamprosate Treatment Outcomes

27. FURTHER QUESTIONS 1. The Role of the Environment 2. The Role of Cognitive Functioning 3. The Time Factor

28. 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

29. Introduction (1) u Importance of "Supportive Treatment" (Social support Brief intervention-motivational Contact) in the follow-up of alcoholic patients is well documented u Studies combining pharmacotherapy and various psychosocial intervention are more seldom u Differential outcome regarding allocation of patients according to "clinical based experience" (Ansoms and coll, Belgium, 2000) or to "Patient - Treatment matching" (Project Match, USA, 1993) is not conclusive CAPRISO STUDY

30. Introduction (2) u Success in implementing a "General helping process" and providing a "General well-being feeling " to the patients during follow-up, seems to be key factors throughout the various psychotherapeutic procedures during follow-up (I. Pelc, 1977 and 1985) u "Although social support has been repeatedly identified as a strong correlate of recovery from alcohol problems, enhancing social support has seldom been a focus of treatment research" (M.B. Sobell and coll., 2000) CAPRISO STUDY

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

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

33. Influence of baseline variables on CAD % % Age Gender p = 0.21 (interaction test) p = 0.33 (interaction test) CAPRISO STUDY

34. Influence of baseline variables on CAD % % Marital status Education % p = 0.09 (interaction test) p = 0.20 (interaction test) CAPRISO STUDY

35. Influence of baseline variables on CAD % % Employment status p = ns (interaction test) CAPRISO STUDY % Family history p = 0.14 (interaction test)

36. Influence of baseline variables on CAD % Cont’d p = 0.008 (interaction test) Attendance to Self Help Group CAPRISO STUDY

37. 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

38. Medication Compliance *: P<0.01 * % visit CAPRISO STUDY

39. 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%