Survey of forty years methadone substitution treatment

1. Survey of forty years methadone substitution treatment

2. Historical 1962 : USA, methadone experimentation by Prof. Vincent Dole, University of Rockefeller, New York First remarkable clinical results Absence of euphoria Decrease in delinquency Abstinence or strong decrease in heroin use Psychosocial reintegration 1970-1980 : fast increase in the development of methadone treatment programmes End 1980 : more than 180�000 patients in treatment

3. Survey of substitution treatments Although controlled programmes with adequate methadone doses adapted to the personal needs of each patient record general success and excellent results, stopping the substitution treatment entails a majority of relapses, frequent loss of acquired quality of life and multiple medical and psychosocial complications.

4. In 1986, Mary-Jeanne Kreek, prof. Rockefeller Institute in New YorkHypothesised that long date heroin addicts: Present a dysfunction in the synthesis, the liberation or the degradation of one or many endorphins; Or a defect in receptor response Kreek MJ, Tolerance and dependence : Implication for the pharmacological treatment of Dependence, 1986.Proceedings of the 48th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, DHHS publication N�(ADM) 87-1508. Rockville, Md, NIDA, US Dept. Of Health and Human Services, 1986, pp. 53-62.

5. Methadone opposition phase False belief of a drug of pleasure Doctors considered as �dealers in white blouses� Drug addict�s fear of social control through methadone False belief of a sort of �chemical lobotomy�

6. War of the therapies:Posters of the opponents in the streets of Geneva

7. Poster in the USA

8. Methadone opposition phase Privileged programmes Quick weaning off of opiates, painful if possible Punishment by incarceration Re-education in therapeutic centres

9. Reasons for the development of methadone programmes AIDS epidemic Fear of AIDS transmission by drug addicts Interest in treating them efficiently Usual failure of quick opiate weaning programmes Very frequent short or average term relapse Worsening of the quality of life Alcohol, cocaine and tranquiliser abuse

10. Outcome of opiate weaning: state of deficit Deep anxiety Sleeping disorders Fatigue, asthenia Irritability Bad feelings of self Relational difficulties Decrease in cognitive functions (attention, memory, concentration) Depressive tendencies Lasts from a few weeks to many months Not very sensitive to antidepressants and neuroleptics Immediately normalised by substitution medication Disturbance of opioid and dopaminergic systems

11. Double-blind procedure and weaning off of methadone (unknown to both patients and therapists) 1mg decrease of methadone a day in 50 stabilised and abstinent (for 2 years) patients After 30 weeks: 90% relapse or psychological decompensation Only 1 patient (2%) was weaned till the end without any problems Newmann R.G. : Double-blind comparison of methadone and placebo maintenance treatment of narcotic addicts in Hong Kong. Lancet, 8141, 485-488,1979

12. Heroin addicts weaned off opiates are abnormally sensitive to stress Opiates (morphine, heroin, methadone) slow the secretion of stress hormonesopiates = calm stress Kreek, MJ : Opiates, opioids and addiction. Molecular Psychiatry 1, 232-254, 1996. Kreek, MJ : Opioid receptors : Some perspectives from early studies of their role in normal psysiology, stress responsivity, and in specific addictive diseases. Neurochemical Research, vol. 21, 11 : 1469-1488, 1996. Kreek, MJ and Koob, GF. Drug dependence : Stress and dysregulation of brain reward pathways. Drug and Alcohol Dependence, 51 : 23-47, 1998.

13. Weaning off of opiates disrupts the stress axis in the long term ACTH blood levels too high in heroin addicts having stopped all treatment for 2 to 3 years and no longer taking drugs Increased stress Increased risk of depression Relapse favoured by weakening of the will, need for compensation and more importantly conditioned reflex

14. Stress and relapse Numerous clinical examples When stressed, the animal that has been weaned for a long time will press the lever that delivers the drug

15. 17 � La m�moire des drogues Ce graphique montre quelque chose de vraiment surprenant � comment la mention d�objets associ�s � l'utilisation de drogues peut causer � un toxicomane une sensation de ��craving�� ou un d�sire de drogue. Ce scan PET fait partie d'une �tude scientifique qui a compar� des toxicomanes sevr�s, qui ont cess� de prendre de la coca�ne, � des personnes qui n'ont jamais pris de coca�ne. Le but de l��tude �tait de d�terminer les parties du cerveau qui sont activ�es quand des drogues sont prises. Pour cette �tude, des scans du cerveau ont �t� pris alors que les sujets observaient deux vid�os. La premi�re vid�o, une pr�sentation de sc�nes sans drogue montrant des images de la nature � montagne, fleuves, animaux, fleurs, arbres. La deuxi�me vid�o montrait des sc�nes li�es � la coca�ne et de paraphernalia de drogue tel que des pipes, des aiguilles, des allumettes et autres articles familiers aux toxicomanes. C�est de cette mani�re que la m�moire des drogues fonctionne: Le secteur jaune sur la partie sup�rieure de la deuxi�me image est l�amygdale, une partie du syst�me limbique du cerveau, qui est critique pour la m�moire et le responsable de l��vocation des �motions. Pour un toxicomane sous craving, l�amygdale devient actif et un craving pour la coca�ne est d�clench�. Ainsi, peut importe que ce soit le milieu de la nuit, qu�il pleuve ou qu�il neige. Ce craving exige de la drogue imm�diatement. Des pens�es raisonnables sont �cart�es par le d�sir incontr�lable pour des drogues. A ce point, un changement de base se produit dans le cerveau. La personne n'est plus sous contr�le. Ce cerveau modifi� rend le toxicomane presque incapable de r�sister � la drogue sans l�aide de professionnels, car l�addiction aux drogues est une maladie du cerveau. Photo de Anna Rose Childress, Ph.D.17 � La m�moire des drogues Ce graphique montre quelque chose de vraiment surprenant � comment la mention d�objets associ�s � l'utilisation de drogues peut causer � un toxicomane une sensation de ��craving�� ou un d�sire de drogue. Ce scan PET fait partie d'une �tude scientifique qui a compar� des toxicomanes sevr�s, qui ont cess� de prendre de la coca�ne, � des personnes qui n'ont jamais pris de coca�ne. Le but de l��tude �tait de d�terminer les parties du cerveau qui sont activ�es quand des drogues sont prises. Pour cette �tude, des scans du cerveau ont �t� pris alors que les sujets observaient deux vid�os. La premi�re vid�o, une pr�sentation de sc�nes sans drogue montrant des images de la nature � montagne, fleuves, animaux, fleurs, arbres. La deuxi�me vid�o montrait des sc�nes li�es � la coca�ne et de paraphernalia de drogue tel que des pipes, des aiguilles, des allumettes et autres articles familiers aux toxicomanes. C�est de cette mani�re que la m�moire des drogues fonctionne: Le secteur jaune sur la partie sup�rieure de la deuxi�me image est l�amygdale, une partie du syst�me limbique du cerveau, qui est critique pour la m�moire et le responsable de l��vocation des �motions. Pour un toxicomane sous craving, l�amygdale devient actif et un craving pour la coca�ne est d�clench�. Ainsi, peut importe que ce soit le milieu de la nuit, qu�il pleuve ou qu�il neige. Ce craving exige de la drogue imm�diatement. Des pens�es raisonnables sont �cart�es par le d�sir incontr�lable pour des drogues. A ce point, un changement de base se produit dans le cerveau. La personne n'est plus sous contr�le. Ce cerveau modifi� rend le toxicomane presque incapable de r�sister � la drogue sans l�aide de professionnels, car l�addiction aux drogues est une maladie du cerveau. Photo de Anna Rose Childress, Ph.D.

16. Neurobiological action of methadone With an individually adequate dosage: neither euphoria nor sedation since: Acquired tolerance through opiate abuse Slow absorption Fixation of 98 % of the methadone on the first hepatic round Progressive liberation by the liver over a period of more than 24 hours Psychomotor tests destined for plain pilots: better performances by methadone patients since less nervous

17. Methadone : remarkable antistress, antidepressant and antipsychotic actions Stabilises opioid systems Slows stress hormones Regulates diverse neuromediators (serotonin, etc.) Stimulates the liberation of dopamine by inhibiting the GABA system, �brake� of the dopamine neurons (blocking of the �brake� = acceleration)

18. International Consensus Drug dependence is a chronic medical illnessMcLellan AT JAMA 2000; 284:1689 -95Office based substitution treatment is an effective treatment for opiate addictionSupportive Articles in: New England Journal of MedecineAnnals of Internal medicineLancetJAMABritish Medical Journal Substitution treatment with relevant social, medical and and psychological services has the highest probability of being the most effective of all available treatments for opiate addiction

19. Correct practice of substitution treatments Maintain at any cost the acquired quality of life: Adequate dosage Optimal length of treatment Qualified psychosocial support

20. Determinig methadone dosage Which dosage should one prescribe ?

21. Low dosage

22. High dosage

23. Individualised  Adequate dosage Based on clinical symptoms and laboratory results

24. How much should on give? ENOUGH

25. How much is enough? The necessary quantity in order to obtain the desired therapeutic response, during the desired lapse of time, with a sufficient security and efficiency margin. Payte et Khuri, 1992.

26. Determining principle of an adequate methadone dosage The absolute indication for increasing methadone dosage is CONTINUED USE OF ILLICIT OPIATES

27. Determining principles of methadone dosage: Levels of methadone in the blood

28. Heroin

29. Methadone

30. Determining principles of methadone dosage: Levels of methadone in the blood

31. Methadone dosage evolution at the Ph�nix Foundation

32. Heroin use decrease

33. Decrease in heroin use according to methadone dosage at the Ph�nix Foundation from 1992 to 2003

34. Dosage and heroin use

35. Quality of psychomotor reflexes, driving capability, degree of attention and concentration; with correct methadone dosage (0 to 100%)

36. Dosage and libido

37. Dosage and free testosterone

38. LH < 3 u/l

39. Direct action of methadone on the hypothalamo-hypophysiary system

40. Lengthening of the QTc and dosage

41. QTc 38 % QTc normal 53 % QTc slightly lengthened 9 % QTc > 10 % Only 1 seriously lengthened QTc

42. Decrease in delinquency

43. HIV seroconversion proportion from 1992 to 2003 6 cases during 11 years 5 cases linked to cocaine Yearly seroconversion mean at the Foundation: 0,5 cases per year For an annual mean of 445 patients, proportion of seroconversion per patient and per year 0,1 %

44. Deaths

45. Psychiatric co-morbidity of patients in methadone treatment B.J. Maron, M.J. Kreek & al : NIDA, Proceeding of the 53th Annual Scientific Meeting Thorough study of 53 men and 50 women 72 % psychological problems before drugs Reduction of 50 % of disorders on methadone Depressive disorders 51 % Phobic disorders 45 % Antisocial personalities 37 % Anxiety 32 % Alcoholism 24 % Obsessive-comp. disorders 20 % Somatic disorders 19 %

46. Ph�nix Foundation survey, 2003 430 questions 371 patients Computerised analyses of results The degree of psychopathology is the most important factor, the most sensitive and best correlated statistically in predicting the quality of treatment results and future prognostic

47. Psychopathology indicator

48. Psychopathology indicator

49. Overdoses before treatment and psychopathology indicator

50. Heroin use before treatment and psychopathology indicator

51. CAGE and psychopathology indicator

52. Number of cocaine intakes over the last 30 days and psychopathology indicator

53. Fulltime work and psychopathology indicator

54. Psychopathology and Invalidity Insurance

55. Community advantages for substitution treatment Remarkable cost � efficiency relationship Strong decrease in Overdoses Delinquency Medical complications AIDS risks Social aid needs Substantial financial economy for the State 1 euro invested in the substitution programmes = 10 euros later economy If there are sufficient methadone treatment programmes Breakdown in heroin dealing Decrease in number of new heroin addicts

56. Who can successfully end substitution treatments? A minority of patients can be weaned off of the substitution medication on the long term Success factors : Minor drug addiction antecedents Lack of notable psychiatric co-morbidity Abstinence for longer than a year Very progressive reduction of methadone of maximum 3% of the dosage per week

57. Psychiatric co-morbidity explains the failure of methadone weaning Genetic defect + environment + factor X Psychiatric co-morbidity Psychological suffering Miraculous discovery of �something better� with drugs Determination to maintain that �something better� Addiction

58. An adequate dosage of methadone balances psychiatric co-morbidity Enables to maintain a good quality of life Facilitates abstinence Decreases delinquency Favours social reinsertion Below a certain dosage, during weaning : Neurobiological imbalance Reappearance of psychiatric co-morbidity Psychological suffering Relapse or desire to return to treatment with normal dosage Just as the trembling of an epileptic reappears when there is a reduction in medication

59. Conclusions 1 For the past 40 years hundreds of thousands of heroin addicts stabilised in the long term by methadone treatment programmes and psychosocial support Unfortunately stopping treatment, even slowly, often fails, even more so for patients with psychiatric co-morbidities For the latter, methadone represents a correcting medication of underlying psychological disorders and must be maintained on the long term just as insulin for diabetics or balancing medication for chronic illnesses

60. Conclusions 2 Necessity of a medical and psychosocial evaluation in order to indicate an eventual weaning In case of failure, relapse after weaning, psychological decompensation or loss of acquired quality of life, necessity to resume treatment with an adequate methadone dosage The most important is to maintain at all costs the psychological balance and good quality of life be it with or without substitution medication