1. Medication Assisted Treatment (MAT) in Pregnant Women
Susan F. Neshin, M.D.
Medical Director
JSAS Healthcare, Inc.
Asbury Park, NJ

2. Overview of Presentation
What is MAT?
Rationale for MAT
Importance of Dose Adequacy
Impact of MAT
The Medications
Women’s Issues/PREGNANCY
Addressing Stigma

3. What is MAT?
MAT=Medication Assisted Treatment in context of substance abuse treatment
EUPHEMISM for opioid maintenance therapy
Methadone
Buprenorphine
Broaden definition
Naltrexone
Medication for other drug dependencies
Medication in the treatment of chronic disease

4. Medications Development Division
Branch of National Institute on Drug Abuse (NIDA)
Developing new medications
Addiction as a brain disease
Drug craving as a physiologic phenomenon

5. Rationale for MAT/OMT For Chronic Opioid Dependence
Dole’s concept of metabolic derangement
Current concept of neuronal adaptations to repeated exposures of the drug
Pre-existing vulnerability and/or consequence of opioid use
Corrective, not curative

6. On/Off - Non-Tolerant Drug States
Overdose
Intoxication
Euphoria
“Normophoria”
Dysphoria
“ON”
Drug Effect
Mood/Effect Scale
“OFF”
No Drug Effect;
“Normal” 6
Opioid Maintenance Pharmacotherapy - A Course for Clinicians

7. Opioid Maintenance Pharmacotherapy - A Course for Clinicians
Heroin Simulated 24 Hr. Dose/Response With established heroin tolerance/dependence
“Loaded”
“High”
“Abnormal Normality”
Normal Range “Comfort Zone”
Dose Response
Subjective w/d
“Sick”
Objective w/d
Time
0 hrs.
24 hrs. 7
Opioid Maintenance Pharmacotherapy - A Course for Clinicians

8. Normal Range “Comfort Zone” Dose Response
Methadone Simulated 24 Hr. Dose/Response At steady-state in tolerant patient
“Loaded”
“High”
“Abnormal Normality”
Normal Range “Comfort Zone”
Dose Response
Subjective w/d
“Sick”
Objective w/d
Time
0 hrs.
24 hrs. 8
Opioid Maintenance Pharmacotherapy - A Course for Clinicians

9. Goals for Pharmacotherapy
Prevention or reduction of withdrawal symptoms
Prevention or reduction of drug craving
Prevention of relapse to use of addictive drug
Restoration to or toward normalcy of any physiological function disrupted by drug addiction

10. Importance of
Dose Adequacy!

11. Recent Heroin Use by Current Methadone Dose
Current Methadone Dose mg/day
J. C. Ball, November 18, 1988

12. Retention in Treatment Relative to Dose
80 + mg
60-79 mg
< 60 mg
Adapted from Caplehorn & Bell - The Medical Journal of Australia

13. Impact of Maintenance Treatment
Reduction death rates (Grondblah, ‘90)
Reduction IVDU (Ball & Ross, ‘91)
Reduction crime days (Ball & Ross)
Reduction rate of HIV seroconversion (Bourne, ‘88; Novick ‘90,; Metzger ‘93)
Reduction relapse to IVDU (Ball & Ross)
Improved employment, health, & social function

14. DEATH RATES IN TREATED AND UNTREATED HEROIN ADDICTS
% Annual Death Rates
Slide data courtesy of Frank Vocci, MD, NIDA - Reference: Grondblah, L. et al. ACTA PSCHIATR SCAND, P , 1990 14

15. Impact of MMT on IV Drug Use for 388 Male MMT Patients in 6 Programs
100%
100
81.4%
63.3%
41.7%
LAST ADDICTION PERIOD
PERCENT IV USERS
ADMISSION *
28.9% *
Pre | 1st Year | 2nd Year | 3rd Year | 4th Year Admission
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

16. Crime among 491 patients before and during MMT at 6 programs
Crime Days Per Year
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

17. HIV CONVERSION IN TREATMENT
18 month HIV conversion by treatment retention Source: Metzger, D. et. al. J of AIDS 6:1993. p.1053

18. OMT as Treatment of Choice for Chronic Relapsing Opioid Addict
Concept of “prolonged abstinence”
Hyper-reactivity to stress
Dysphoria/craving increase vulnerability to relapse

19. Relapse to IV drug use after MMT 105 male patients who left treatment
Percent IV Users
Treatment Months Since Stopping Treatment
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

20. The Medications Methadone Long-acting full opioid agonist
Orally effective
Can be taken once a day
Prescribed and dispensed at licensed OTPs

21. The Medications Buprenorphine Approved by FDA in October, 2002
Result of DATA 2000
Long-acting partial opioid agonist
Sublingually effective
Can be taken once a day or less frequently
Prescribed by private practitioner with waiver

22. The Medications Naltrexone Long-acting opioid antagonist
Orally effective
Can be taken once a day or less frequently
Benefits subgroups of opioid addicts

23. Addiction as a Biopsychosocial Disease
OMT addresses the biological aspect
Psychosocial aspects addressed
Substance abuse counseling
Mental health treatment
Support and self-help groups
Accreditation standards
Should improve treatment
Eliminate “gas and go” model

24. Women’s Issues Higher levels of dual diagnosis than men Childcare
Transportation
Domestic Violence
Educational/Vocational
Financial
Pregnancy

25. How to Address Women’s Issues
Accreditation standards
Variable levels of resources
Women’s Set-Aside funds
One-stop shopping

26. Dual Diagnosis Depression/mood disorders Anxiety disorders/PTSD
Eating disorders
Symptoms
Guilt and shame
Low self esteem

27. Dual Diagnosis Train counseling staff Availability of therapist
Availability of psychiatrist
Staff with expertise in “survivor” issues
Lifetime prevalence of drug abuse > 4 times greater in women who report history of sexual assault
Support/therapy groups

28. Childcare Issues Most women in treatment are of childbearing age
Children as barrier to treatment
Services to address
Children welcome
On-site child care
Parenting classes

29. Transportation Issues
Lack of transportation as barrier to treatment
Clinics in “out of the way” areas
Services to address
Use of medical transportation for Medicaid patients
Site program close to public transportation
Give “take-homes” when earned
Van service
Home medication/family member pick-up for homebound patients

30. Domestic Violence Train staff
Facilitate referral to shelter when appropriate
Support/therapy group

31. Educational/Vocational Issues
Most women in treatment are “undereducated” and “underemployed”
Services to address:
Train staff about community resources/state-funded programs
On-site vocational counselor
Address “sex for drugs” issues

32. Financial Issues Treatment is expensive
Proprietary vs. publicly-funded non-profit programs
Services to address patient issues
Accept Medicaid as payment
Allow for reduced fee/indigency
Counsel on budgeting
Counselor referrals to/interventions with local service agencies

33. Financial Issues Program issues Fund raising
Lobbying for higher state/federal funding

34. Considerations for Treatment of Pregnant Opiate Addict
Tolerance level
Chronicity of use
Route of administration
Pregnancy history
Motivational level
Recovery environment
Ideal vs. Reality

35. OMT/MAT as Standard of Care
Steady levels of opiates normalize neuroendocrine functioning and prevent fetal distress
Decreases rates of pregnancy complications, e.g. miscarriage, stillbirth, IUGR, abruptio placenta, infection, hemorrhage
Improves prenatal care
Allows for psychosocial interventions to improve level of functioning

36. Perinatal Addiction Importance of pregnancy testing at intake
Priority admission should be given to pregnant patients
Family planning as counseling issue with periodic pregnancy testing, especially during medically supervised withdrawal
Dose of methadone should be individually determined and adequate to control craving and prevent withdrawal syndrome

37. Perinatal Addiction
MMT patients who become pregnant should be continued at established dose. A mid-trimester reduction may be appropriate in anticipation of 3rd trimester dose increase.
Altered pharmacokinetics during 3rd trimester often require dose increases and often a split dose to “flatten the curve” and improve maternal and fetal stability.

38. Perinatal Addiction
There is no consistent correlation between maternal methadone dose and the severity of neonatal withdrawal syndrome (Stimmel et al., 1982).
Protocols are available for scoring signs of opioid withdrawal to guide the appropriate use of medications to facilitate a safe and comfortable withdrawal of the passively addicted neonate (Finnegan, 1985).

39. Perinatal Addiction
Breast-feeding may be encouraged during MMT - if not otherwise contraindicated (Kaltenbach, 1992).
Multiple longitudinal studies find that methadone-exposed infants score well within the normal range of development (Kaltenbach, 1992).

40. Perinatal Addiction
Obstacles and barriers to MMT must be removed for the pregnant patients.
More research is needed on innovative models of treatment including medically supervised withdrawal during pregnancy with residential care, intensive relapse prevention and monitoring, high-risk prenatal care. When appropriate hospitals, clinics and individual obstetricians could provide methadone maintenance.

41. Withdrawal during Pregnancy
Rarely appropriate during pregnancy (ASAM 1990)
Same recidivism as non-pregnant opioid addicts
Slow withdrawal between 14 and 32 week
Patient lives in an area where MM is not available.
Patient refuses to be placed on MM.
Patient has been stable and requests withdrawal prior to delivery.

42. Withdrawal during Pregnancy
No harm reduction with OMT
Patient has been so disruptive to the treatment setting that the treatment of other patients is jeopardized, necessitating the removal of the patient from the program.

43. Pregnancy
Comprehensive OMT with adequate prenatal care can reduce the incidence of obstetrical and fetal complications, in utero growth retardation, and neonatal morbidity and mortality (Finnegan, 1991).

44. Model Perinatal Program
On-site prenatal care
On-site well-baby care
On-site child care
Educational groups
Pregnancy/medical issues
Methadone and pregnancy
Effects of drugs of abuse, including alcohol and nicotine, on fetus

53. Model Perinatal Program
Educational groups--continued
Nutrition
Baby care
Parenting skills--include fathers
Contraception/Family Planning
Domestic Violence

54. Model Perinatal Program
Counseling on pregnancy termination and adoption
On-Site Psychiatric/Psychological evaluation and treatment

55. Use of Psychotropic Medication During Pregnancy
Weigh risks vs. benefits
Inform patient of drug’s potential for teratogenic or other adverse effects (Category)
Consider consequences of untreated psychiatric illness
Use lowest effective dose

56. Antidepressants in Pregnancy
No increase in major malformations
?cardiac defects with paroxetine
No increase in long term neurodevelopmental adverse outcomes
SSRI’s in third trimester
may see withdrawal syndrome in neonate
increase in persistent pulmonary hypertension
no long term residual effects
Tricyclics relatively safe
MAI inhibitors contraindicated

57. Benzodiazepines During Pregnancy
Slight increase in oral clefts
Possible withdrawal syndrome
No long term neurodevelopmental adverse effects

58. Risks of Untreated Depression
Increase in miscarriage, hypertension and preeclampsia
Increase in likelihood of relapse to depression with stopping antidepressant medication
Global IQ negatively associated with duration of depression
Language development negatively correlated with number of postnatal depressive episodes

63. Addressing Stigma EDUCATE OURSELVES! “I don’t believe in methadone!”
ASAM addressing physician bias
Arizona study -- 96% refusal to treat or give pain meds
Example of physician opioid addict

64. Addressing Stigma EDUCATE OURSELVES!--continued
Need to educate therapeutic communities, Minnesota model programs
Need to educate Twelve Step community
Methadone/buprenorphine as prescribed medications rather than drugs of abuse
Patients on OMT can work a program of recovery

65. Addressing Stigma Educate service agencies and the general public
Arizona study -- 66% refused employment or lost job
Educate patients about the chronic disease concept
Methadone/buprenorphine as corrective, not curative
Educate family members

66. Addressing Stigma
Publicly funded programs should be mandated to accept patients on OMT
Private programs should be encouraged to accept patient on OMT
Great need for residential treatment/halfway houses for women (pregnant or non-pregnant) and their children

67. Addressing Stigma
Patients should be encouraged to get involved in advocacy
Patients need to risk divulging status to treatment providers with support from program staff