Survey of forty years methadone substitution treatment

1
Survey of forty years methadone substitution
treatment
SKOUN New perspectives for the treatment and
prevention of addiction 7-9 of October
2005 Beyrouth
Dr Jean-Jacques Déglon, Eva Wark et coll. Phenix
Foundation, Geneva
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 180000 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 addicts fear of social control through
  methadone
• False belief of a sort of chemical lobotomy

6
War of the therapiesPosters 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
Memory of drugs
Amygdalianot acitvated
Activation of theamygdalia
Front of brain
Back of brain
Video of a cocaine scene
Video of nature
Drug addiction is an illness of the brain.
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
2841689 -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
Joseph al, 2000 AATOD Drug Court Fact Sheet,
2002
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
Never speak in terms of
22
High dosage
Never speak in terms of
23
Individualised Adequate dosage
Speak in terms of.

• 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
Source DOLE, V.P. NYSWANDER, M.E.,
Pharmacological Treatment of Narcotic Addiction
(The Eight Nartan B. Memorial Award Lecture),
NIDA, 1982.
29
Methadone
Source DOLE, V.P. et NYSWANDER, M.E.,
Pharmacological Treatment of Narcotic Addiction
(The Eight Nartan B. Memorial Award Lecture),
NIDA, 1982.
30
Determining principles of methadone dosage
Levels of methadone in the blood
CSAT
31
Methadone dosage evolution at the Phénix
Foundation
32
Heroin use decrease
33
Decrease in heroin use according to methadone
dosage at the Phénix Foundation from 1992 to 2003
34
Dosage and heroin use
Survey 2003
35
Quality of psychomotor reflexes, driving
capability, degree of attention and
concentration with correct methadone dosage (0
to 100)
Survey 2003
36
Dosage and libido
Survey 2003
37
Dosage and free testosterone
Survey 2003
38
LH lt 3 u/l
39
Direct action of methadone on the
hypothalamo-hypophysiary system
With low levels of testosterone and abnormally
low levels of LH and FSH without prolactine
increase
Likely inhibiting 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 gt 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
Phénix 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
Based on 28 parameters (max 330 points)
Survey 2003
49
Overdoses before treatment and psychopathology
indicator
Survey 2003
50
Heroin use before treatment and psychopathology
indicator
Survey 2003
51
CAGE and psychopathology indicator
Survey 2003
52
Number of cocaine intakes over the last 30 days
and psychopathology indicator
53
Fulltime work and psychopathology indicator
54
Psychopathology and Invalidity Insurance
Survey 2003
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