Club Médical Interhospitalier du HainautSymposium 2002

« L ’utilisation clinique du CAMPRAL »

Prof. I. Pelc CHU Brugmann - ULBBruxelles - Belgique

MENTAL HEALTH CHARACTERISTICS

bio

psycho

social

aspects

ACAMPROSATE

Acetyl homotaurinate de calcium

CH3-CO-NH-CH2-CH2-CH2-SO3

CH3-CO-NH-CH2-CH2-CH2-SO3

Ca

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

Campral®: A NOVEL ACTION IN

ALCOHOL DEPENDENCENORMALNORMAL CHRONIC ALCOHOLISMCHRONIC ALCOHOLISM

BALANCE

WITHDRAWALWITHDRAWAL CRAVINGCRAVINGHYPEREXCITATION

BALANCE

Inh Exc Inh Exc

BAR Alc+

Exc BRAIN+

BAR AlcInh

Exc

Exc BRAIN+

Inh

Exc

Exc BRAIN+ (learned

association)

Inh Exc

Campral® + CRAVING BRAIN

(learned association)

META-ANALYSIS Method of Hedges & Olkin, 1985

Included 15 randomized placebo-controlled, double-Included 15 randomized placebo-controlled, double-blind studiesblind studies

performed in 11 European countriesperformed in 11 European countries involved over 4,400 alcohol-dependent outpatientsinvolved over 4,400 alcohol-dependent outpatients

Confirmed the significant effect of acamprosate versus Confirmed the significant effect of acamprosate versus placebo on abstinence parametersplacebo on abstinence parameters

Supports the generalizability of acamprosate data Supports the generalizability of acamprosate data

0

100

200

300

400

500

600

700

STUDY SIZE

CUMULATIVE ABSTINENCE DURATION PROPORTION

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

Campral

Placebo

*

*

*p < 0.05

**

**

**

*

* *

0

20

40

60

80

100

120

140

160

180

Paille et al, '95

Sass et al, '96

Whitworth et al, '96

Barrias et al, '97

Geerlings et al, '97

Pelc et al, '97

Poldrugo, '97

Chick et al, '00

Tempesta et al, '00

AcamprosatePlacebo

ACAMPROSATE EUROPEAN DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

Days to First Drink

ACAMPROSATE EUROPEAN DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

Rate of Total Abstinence (%)

0%

10%

20%

30%

40%

50%

60%

Lhuintre et al, '85

Pelc et al, 92

Ladewig et al, '93

Paille et al, '95

Rousseaux et al, '96

Sass et al, '96

Whitworth et al, '96

Barrias et al, '97

Geerlings et al, '97

Pelc et al, '97

Poldrugo, '97

Besson et al, '98

Chick et al, 00

Tempesta et al, '00

Gual et al. '01

Acamprosate

Placebo

Overall Mean %:

Acamprosate = 35.7%

Placebo = 21.9%

D = 13.8%

40

50

60

70

80

90

100

0 30 90 180 270 360

Acamprosate Placebo

***

**

*: p<0,001

N = 3,338 N = 2,876 N = 958N = 2,262 N = 866N = 1,679

%

Days

ABSTINENCE RATES FOR PATIENTS WHOREMAINED IN THE TRIALS

Percentage of patients abstinent(treatment duration 3-12 months)

0

10

20

30

40

50

60

70

80

90

100

Acamprosate

Placebo

Continuous abstinence: time to first drink

% P

atie

nts

Treatment Period Follow-up Period

Never had a drink

FOLLOW-UP PERIOD(Sass et al.)

600 120 180 240 300 360 420 480 540 660600 720

EFFECT OF CAMPRAL ON ABSTINENCE RATE, CUMULATIVE ABSTINENCE

DURATION, COMPLIANCE TO TREATMENT AND CLINICAL GLOBAL IMPRESSION

0

10

20

30

40

50

60

Acamprosate Placebo

Results after 180 treatment daysPelc IBELGIUM

*

*

*

**

* p<0.05** p<0.005

Abstinence rate CAD Compliance CGI

Days

% P

atie

nts

0 50 100 150 200 250

Group therapy + CAMPRAL

Individual therapy +CAMPRAL

Cognitive therapy + CAMPRAL

Brief intervention + CAMPRAL

Total

Cumulative Abstinence Duration in daysby intervention type (per protocol)

THERE IS NO DIFFERENCE IN CAD BETWEEN DIFFERENT TYPES

OF PSYCHOTHERAPY IN PATIENTS ON Campral®

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 = seldom2 = sometimes 3 = frequentlyaccording 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 = seldom2 = sometimes 3 = frequentlyaccording 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 = seldom2 = sometimes 3 = frequentlyaccording 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 timeand interrater reliability:0 = never 2 = sometimes1 = seldom 3 = frequently

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

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 collUniversity Hospital Brugmann Université Libre de BruxellesBELGIUM

CAPRISO STUDY

Efficacy Variables

Cumulative abstinence duration

(CAD) in per cent

Clinical Global Impression

Medication compliance

CAPRISO STUDY

Cumulative abstinence days (%)

39

55

0

10

20

30

40

50

60

ITT

No Fu

Fu

p < 0.23

CAPRISO STUDY

51

65

4135

0

20

40

60

No SHG SHG

Fu

No Fu

Influence of baseline variables on CAD % Cont’d

p = 0.008 (interaction test)

Attendance to Self Help Group

CAPRISO STUDY

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: R2 = .49

CAPRISO STUDY

Rate of Complete Abstinence throughout a 6 month Period Evaluation after Detoxification

CAPRISO STUDY

RandomizedPlacebo-controlled

Study *

RandomizedPsycho-social follow-up

Study **

N = 104 N = 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%