Medication Assisted Treatment (MAT)

in Pregnant Women

Susan F. Neshin, M.D.

Medical Director

JSAS Healthcare, Inc.

Asbury Park, NJ

E-mail: jsasmd@aol.com

Overview of Presentation

• What is MAT?

• Rationale for MAT

• Importance of Dose Adequacy

• Impact of MAT

• The Medications

• Women’s Issues/PREGNANCY

• Addressing Stigma

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

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

Rationale for MAT/OMTFor 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

On/Off - Non-Tolerant Drug StatesOn/Off - Non-Tolerant Drug StatesM

oo

d/E

ffe

ct

Sc

ale “ON”

Drug Effect

“OFF”

No Drug Effect;

“Normal”

Overdose

Intoxication

Euphoria

“Normophoria”

Dysphoria

Opioid Maintenance Pharmacotherapy - A Course for Clinicians6

Do

se R

esp

on

se

Time

“Loaded” “High”

Normal Range“Comfort Zone”

“Sick”

Heroin Simulated 24 Hr. Dose/Response

With established heroin tolerance/dependence

0 hrs.

24 hrs.

“Abnormal Normality”

Subjective w/d

Objective w/d

Opioid Maintenance Pharmacotherapy - A Course for Clinicians7

Do

se R

esp

on

se

Time

“Loaded” “High”

Normal Range“Comfort Zone”

“Sick”

Methadone Simulated 24 Hr. Dose/ResponseAt steady-state in tolerant patient

0 hrs.

24 hrs.

“Abnormal Normality”

Subjective w/d

Objective w/d

Opioid Maintenance Pharmacotherapy - A Course for Clinicians

8

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

Importance of

Dose Adequacy!

Recent Heroin Use by Current Methadone Dose

0

20

40

60

80

100

120

0 10 20 30 40 50 60 70 80 90 100

Current Methadone Dose mg/day

% H

ero

in U

se

J. C. Ball, November 18, 1988

Retention in Treatment Relative to Dose

0 20 40 60 80 100

80 + mg

60-79 mg

< 60 mg

Adapted from Caplehorn & Bell - The Medical Journal of Australia

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

DEATH RATES IN TREATED AND UNTREATED HEROIN

ADDICTS

0

1

2

3

4

5

6

7

8

MMT VOL DC TX INVOL DC TX UNTREATED

OBSERVEDEXPECTED

Slide data courtesy of Frank Vocci, MD, NIDA - Reference: Grondblah, L. et al.

ACTA PSCHIATR SCAND, P. 223-227, 1990

% A

nn

ua

l De

ath

Rat

es

14

Impact of MMT on IV Drug Use for 388 Male MMT Patients in 6 Programs

PE

RC

EN

T I

V U

SE

RS

0

100

LA

ST

AD

DIC

TIO

N P

ER

IOD

AD

MIS

SIO

N

100%

81.4%

Pre- | 1st Year | 2nd Year | 3rd Year | 4th Year Admission

*

*

63.3%

41.7%

28.9%

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

Crime among 491 patients before and during MMT at 6 programs

0

50

100

150

200

250

300

A B C D E F

Before TX

During TX

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

Cri

me

Day

s P

er Y

ear

HIV CONVERSION IN TREATMENT

0%

5%

10%

15%

20%

25%

In Tx (N=95) Partial Tx(N=45)

No Tx (N=55)

Tx Status

18 month HIV conversion by treatment retentionSource: Metzger, D. et. al. J of AIDS 6:1993. p.1053

OMT as Treatment of Choicefor Chronic Relapsing Opioid

Addict

• Concept of “prolonged abstinence”

– Hyper-reactivity to stress

– Dysphoria/craving increase vulnerability to relapse

Relapse to IV drug use after MMT105 male patients who left treatment

28.9

45.5

57.6

72.2

82.1

0

20

40

60

80

100

IN 1 to 3 4 to 6 7 to 9 10 to 12

Pe

rce

nt

IV U

se

rs

Treatment Months Since Stopping Treatment

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

The Medications

• Methadone

– Long-acting full opioid agonist

– Orally effective

– Can be taken once a day

– Prescribed and dispensed at licensed OTPs

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

The Medications

• Naltrexone

– Long-acting opioid antagonist

– Orally effective

– Can be taken once a day or less frequently

– Benefits subgroups of opioid addicts

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

Women’s Issues

• Higher levels of dual diagnosis than men

• Childcare

• Transportation

• Domestic Violence

• Educational/Vocational

• Financial

• Pregnancy

How to Address Women’s Issues

• Accreditation standards

• Variable levels of resources

• Women’s Set-Aside funds

• One-stop shopping

Dual Diagnosis

• Depression/mood disorders

• Anxiety disorders/PTSD

• Eating disorders

• Symptoms

– Guilt and shame

– Low self esteem

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

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

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

Domestic Violence

• Train staff

• Facilitate referral to shelter when appropriate

• Support/therapy group

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

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

Financial Issues

• Program issues

– Fund raising

– Lobbying for higher state/federal funding

Considerations for Treatment of Pregnant Opiate Addict

• Tolerance level

• Chronicity of use

• Route of administration

• Pregnancy history

• Motivational level

• Recovery environment

• Ideal vs. Reality

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

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

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.

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).

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).

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.

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.

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.

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).

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

Model Perinatal Program

• Educational groups--continued

– Nutrition

– Baby care

– Parenting skills--include fathers

– Contraception/Family Planning

– Domestic Violence

Model Perinatal Program

• Counseling on pregnancy termination and adoption

• On-Site Psychiatric/Psychological evaluation and treatment

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

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

Benzodiazepines During Pregnancy

• Slight increase in oral clefts

• Possible withdrawal syndrome

• No long term neurodevelopmental adverse effects

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

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

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

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

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

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