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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
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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 = never 1 = seldom 2 = sometimes 3 = frequently according to the global situation during the last 6 months
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 = never 1 = seldom 2 = sometimes 3 = frequently according to the global situation during the last 6 months
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 = never 1 = seldom 2 = sometimes 3 = frequently according to the global situation during the last 6 months
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 = never 2 = sometimes 1 = seldom 3 = frequently
ANGER 70 % This person feels anger 1 2 3 4 5 6 7 Not at all Very intensively
INTENSITY SCORES AS FUNCTION OF GROUP AND FACIAL EXPRESSION I n t e n s i t y s c o r e s Emotional Facial Expressions Note. * p<.05; ** p<.01 Kornreich et al. (2001) Journal of Studies on Alcohol
COMPARISONS BETWEEN PERFORMANCES ON THE SERIAL AND THE ALPHABETICAL RECALL SCORES ON THE ALPHA-SPAN TEST S c o r e Effect of group: F1,58=43.6, p<.001; Effect of condition: F1,58=90.9, p<.001 Interaction between group and condition: F1,58=54.6, p<.001 * Post-hoc analysis indicated that ALC performed lower only in alphabetic recall (p<.01)
AVERAGE NUMBER OF ERRORS MADE BY ALCOHOLICS AND CONTROLS ON THE HAYLING TEST P o i n t s o f p e n a l t y Note. *** p<.001
drug RELATIONSHIP BETWEEN POSITIVE AND NEGATIVE REINFORCEMENT drug POSITIVE REINFORCEMENT chemical drug reward Glu, GABA, DA/endorphins adapt CHRONIC DRUG TOLERANCE neurochemical adaptation Glu RS, GABAA Rs, ? DA/Es adapt drug drug adapt adapt 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
CONDITIONING OF REINFORCEMENTS = CRAVING? Repeated pairing "conditions" associated stimulus ("cue") D D D + CUE + CUE + CUE POSITIVE ASPECTS OF CRAVING Conditioned stimulus (cue) elicits anticipation of drug reward e.g. relaxation, euphoria, excitement CUE A A Cue becomes conditioned stimulus for adaptation D D A D + CUE + CUE + CUE A NEGATIVE ASPECTS OF CRAVING Conditioned stimulus (cue) elicits "pseudo-withdrawal" e.g. anxiety, dysphoria, depression, tremor, etc. CUE
THE MECHANISMS OF ALCOHOL DEPENDENCE Adaptation to alcohol as the basis for the Withdrawal Syndrome Excitation Littleton JM. Addiction, 1995 CNS ACTIVITY Withdrawal syndrome Acute effect Development of tolerance Inhibition Withdrawal Alcohol administration Exposure of adaptation causes hyperexcitation Immediate CNS depressant effects of ethanol become limited by neurochemical adaptation
Campral®: A NOVEL ACTION IN ALCOHOL DEPENDENCE NORMAL CHRONIC ALCOHOLISM BRAIN BAR Alc Exc + + BALANCE Exc Inh Inh Exc WITHDRAWAL CRAVING HYPER EXCITATION BAR Alc Exc BRAIN Inh Exc BRAIN Inh + (learned association) + Exc Exc BALANCE BRAIN Campral® + CRAVING (learned association) Inh Exc
Campral® EFFECT OF Campral® ON DISRUPTED NEUROTRANSMISSION GABA GABA GABA + Acute alcohol intake Chronic exposure to alcohol Adaptation EAA - EAA* *Excitatory Amino Acids Glutamate in particular EAA
META-ANALYSIS Method of Hedges & Olkin, 1985 • Included 15 randomized placebo-controlled, double-blind studies • performed in 11 European countries • involved over 4,400 alcohol-dependent outpatients • Confirmed the significant effect of acamprosate versus placebo on abstinence parameters • Supports the generalizability of acamprosate data
CUMULATIVE ABSTINENCE DURATION PROPORTION * * * * * * * * * * * *p < 0.05
ACAMPROSATE EUROPEAN DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALSDays to First Drink
ACAMPROSATE EUROPEAN DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALSRate of Total Abstinence (%) Overall Mean %: Acamprosate = 35.7% Placebo = 21.9% D = 13.8%
RESULTS: % ABSTAINERS IN PATIENTS ON TREATMENT 5 TRIALS (TREATMENT DURATION: 12 MONTHS) % *: p<0,001 * * * * * Days
ABSTINENCE RATES FOR PATIENTS WHO REMAINED IN THE TRIALS Percentage of patients abstinent(treatment duration 3-12 months) % *: p<0,001 * * * * * Days N = 3,338 N = 958 N = 2,876 N = 866 N = 1,679 N= 2,262
FOLLOW-UP PERIOD (Sass et al.) Continuous abstinence: time to first drink 100 90 80 70 60 Acamprosate % Patients 50 Never had a drink 40 30 Placebo 20 10 0 0 120 180 240 300 360 420 480 540 600 660 720 60 Treatment Period Follow-up Period
EFFECT OF CAMPRAL ON ABSTINENCE RATE, CUMULATIVE ABSTINENCE DURATION, COMPLIANCE TO TREATMENT AND CLINICAL GLOBAL IMPRESSION Pelc I BELGIUM Results after 180 treatment days * p<0.05 ** p<0.005 ** * * % Patients * Abstinence rate CAD Compliance CGI Days
NEW EUROPEAN ALCOHOLISM TREATMENT (NEAT) ACAMPROSATE PROGRAM • Open label, multicenter, multinational (5) • 1 281 alcohol-dependent patients • 6-month study duration • Concurrent group, individual, relapse prevention or brief intervention therapy • Comparisons of acamprosate efficacy across therapy conditions found • significant improvement in all groups in maintaining abstinence and reducing relapse duration • no difference between behavioral therapy groups
THERE IS NO DIFFERENCE IN CAD BETWEEN DIFFERENT TYPES OF PSYCHOTHERAPY IN PATIENTS ON Campral® Cumulative Abstinence Duration in days by intervention type (per protocol)
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
CONCLUSIONS (2) Acamprosate Treatment Outcomes CAD values in the NEAT were similar to those in randomised controlled studies Acamprosate increases QoL in enhancing abstinence. Abstinence Acamprosate QOL •
FURTHER QUESTIONS 1. The Role of the Environment 2. The Role of Cognitive Functioning 3. The Time Factor
CAPRISO STUDY 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 • Introduction (1) • Importance of "Supportive Treatment" (Social support Brief intervention-motivational Contact) in the follow-up of alcoholic patients is well documented • Studies combining pharmacotherapy and various psychosocial intervention are more seldom • 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 • Introduction (2) • 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) • "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 Efficacy Variables • Cumulative abstinence duration (CAD) in per cent • Clinical Global Impression • Medication compliance
CAPRISO STUDY Cumulative abstinence days (%) p < 0.23
CAPRISO STUDY Influence of baseline variables on CAD % % Age p = 0.33 (interaction test) Gender p = 0.21 (interaction test)
CAPRISO STUDY Influence of baseline variables on CAD % % Marital status p = 0.20 (interaction test) % Education p = 0.09 (interaction test)
CAPRISO STUDY Influence of baseline variables on CAD % % Family history p = 0.14 (interaction test) % Employment status p = ns (interaction test)
CAPRISO STUDY Influence of baseline variables on CAD % Cont’d Attendance to Self Help Group p = 0.008 (interaction test)
CAPRISO STUDY Structural modelling representation of regression analysis on CAD Education 0.12 Marital status 0.19 CAD 0.29 F.U. -0.24 Female -0.22 SHG + Regression analysis: R2 = .49
CAPRISO STUDY Medication Compliance % * visit *: P<0.01
CAPRISO STUDY Rate of Complete Abstinence throughout a 6 month Period Evaluation after Detoxification Randomized Psycho-social follow-up Study ** Randomized Placebo-controlled Study * N = 104 N = 100 Acamprosate No Fu Fu 14% 32% Placebo Acamprosate 4% 24% * 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