Drug Treatment Issues in DrugDependent, Pregnant Women

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Drug Treatment Issues in Drug-Dependent, Pregnant
Women

• Hendrée E. Jones, Ph.D. Department of Psychiatry
• and Behavioral SciencesJohns Hopkins University
  School of Medicine
• Baltimore, Maryland

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Disclosure

• During this presentation at the annual APA
  meeting, Dr. Jones will be discussing the uses of
  commercial products not yet approved for this
  purpose by the FDA. She has no actual or
  potential conflict of interest in regards to this
  program.

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Presentation Goals

• Use of medication to treat opioid dependence
  during pregnancy
• Clinical trial of methadone and buprenorphine
  during pregnancy
• Behavioral interventions enhance maternal
  outcomes

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Studies of Medication During Pregnancy

• Controversial
• Some say unethical
• Stigma associated with medication treatment for
  pregnant women is severe

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Goals of Opioid Agonist Treatment

• Cessation of opioid use
• Stabilize intrauterine environment
• Increased prenatal care compliance
• Enhanced pregnancy outcomes

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Methadone is effective during pregnancy

• Methadone is recommended for the treatment of
  opioid-dependent women
• Over 30 years of experience and research
• Not appear to have teratogenic potential

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Neonatal Abstinence Syndrome (NAS)

• Neuralgic excitability (hyperactivity,
  irritability, sleep disturbance)
• Gastrointestinal dysfunction
• (uncoordinated sucking/swallowing, vomiting)
• Autonomic Signs (fever, sweating, nasal
  stuffiness)

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The NAS of Opioid-Exposed Neonates

• 55-90 exhibit NAS
• Methadone dose relationship to NAS severity
  is inconsistent
• Onset within 48 to 72 hours after birth
• Subacute signs up to 12 months

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Buprenorphine

• A derivative of thebaine
• Marketed as Subutex or
  Suboxone

Full
Full
Antagonist
Agonist
Heroin
Buprenorphine
Nalmefene
Naloxone
Morphine
Naltrexone
Methadone
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Buprenorphine

• Birth outcomes improved with agonist therapy
  (e.g., methadone)
• Withdrawal associated with agonist therapy can
  require hospitalization
• Buprenorphine reported to produce less physical
  dependence in adults

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Case Reports and Open-Label Studies

• Since 1995, 23 reports of prenatal exposure to
  buprenorphine
• 22 reports from Europe and 1 from U.S.
• Number of cases ranged from 1 to 153 (median6)
• TOTAL 338 babies

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Outline

• Use of medication to treat opioid dependence
  during pregnancy
• Clinical trial of methadone and buprenorphine
  during pregnancy
• Behavioral interventions enhance mother and child
  outcomes

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Randomized Controlled Study

• Double-blind (staff and patient)
• Double-dummy (two medications)
• Two groups Methadone or Buprenorphine
• Flexible dosing
• Methadone 40-100 mg
• Buprenorphine 4-24 mg

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Setting Center for Addiction Pregnancy

• Interdisciplinary Approach
• Psychiatry
• Obstetrics
• Pediatrics
• Nursing

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Criteria

• Inclusion
• 18 - 40 years of age
• Gestational age 16 - 30 weeks
• Opioid dependent (DSM-IV, SCID I)
• Recent opioid use
• Opioid positive urine

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Criteria

• Exclusion
• Methadone positive urine at admission
• DSM IV axis I current diagnosis other than
  psychoactive substance use
• Serious medical or psychiatric illness
• Diagnosis of preterm labor
• Congenital fetal malformation
• Current alcohol abuse/dependence
• Benzodiazepine use
• (8 or more times/month and/or 2 or more
  times/week)

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Primary Outcome Measures
Infant

• Neonatal Abstinence Syndrome
• (NAS)
• Length of Hospital Stay
• (LOS)

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Selected Secondary Outcome Measures

• Maternal
• Days of treatment
• Prenatal care visits
• Illicit drug use
• Infant
• Physical birth parameters

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Patient Flow
Number screened 1490
Not Qualify Initially 1433
Qualify and sign consent 57
Randomized 30
Buprenorphine 15
Methadone 15
Buprenorphine 9
Methadone 11
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Induction

• Patients stabilized on immediate release morphine
  (IRM) prior to randomization
• Is transition from IRM to methadone or
  buprenorphine similar?
• Withdrawal scores over first 3 days appeared mild
  for both medications

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Maternal OutcomeDrug Use During Pregnancy
Methadone N11
Buprenorphine N9
opioid 15.6 16.7 cocaine 11.2 15.2
amphetamine 0.0 0.0 barbiturates
0.0 0.0 benzo 0.4 2.5 THC
7.5 0.0
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Maternal Characteristics
Methadone N11
Buprenorphine N9
African-American 63.6 88.9 EGA
(weeks) 23.6 22.8 Education
(yrs) 10.0 10.3 Employed 0.0 0.0 Age
(yrs) 30.3 30.0
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Maternal Outcomes
Methadone N11
Buprenorphine N9
Days in Treatment 99.9 115.6 Prenatal
care visits 3.4 3.6 LOS mom 2.2
2.2 C section 9.1 11.1 Tox. delivery
(mom) 9.1 0.0 normal presentation 100
100 Preterm birth 9.1 0.0 Gestational
age delivery 38.8 38.8 Ave. dose at delivery
(mg) 79.1 18.7
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Birth Outcomes
Methadone N11
Buprenorphine N9 deliveries (10 babies)
Treated 45.5 20.0 Birth Weight (gm)
3001.8 3530.4 LOS baby 8.1 6.8
NICU treatment 18.0 10.0 APGAR 1 8.3
8.1 APGAR 5 8.9 8.7 Length
(cm) 49.6 52.8 Head Cir. (cm) 33.2 34.9 Tox
(Baby) 0.0 20.0
data safety monitoring board recommended
removing twin data from these variables
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Limitations of Study

• Small sample size
• I/E criteria limits generalizability
• Nicotine exposure and effect on NAS needs more
  study
• Long-term outcomes beyond scope of study

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Conclusions

• Both methadone and buprenorphine provide positive
  benefits to mothers
• 100 of infants had NAS signs/symptoms
• Tendency for fewer buprenorphine-exposed babies
  to be treated for NAS
• Significantly fewer days of hospitalization with
  buprenorphine exposure

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Bottom Line

• Both medications have strong support to document
  safety and efficacy for mother and infant
• NAS is only part of the complete riskbenefit
  ratio
• More medication options will improve the
  treatment of pregnant women

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Issues Pregnant, Drug-Dependent Women Face

• Unstable housing
• Victimization and violence
• physical
• sexual
• emotional
• Severe stigma
• Other psychiatric issues

• Multigenerational
• drug use
• Lack of education
• Maladaptive behaviors
• poor self-control
• trust issues
• Legal
• Parenting

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Presentation Goals

• Use of medication to treat opioid dependence
  during pregnancy
• Clinical trial of methadone and buprenorphine
  during pregnancy
• Behavioral Interventions enhance maternal outcomes

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Types of Behavioral Interventions Examined at CAP

• Contingency Management
• Rewards for drug-abstinence include housing, gift
  certificates, goods and services
• Community Reinforcement Approach
• Motivational Interviewing

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Relationships as Barriers to Treatment

• Female drug use starts and continues in context
  of male romantic relationships
• Level of partner support impacts outcomes among
  pregnant methadone-maintained women (Jeremy,
  1984 Marcus, 1984)

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Womens Treatment Retention

• Mean relationship of 4 yrs
• Drug using partners
• -less employed
• - less supportive
• of womans treatment
• -more legal involvement
• -more dental and
• medical needs

PDependence (2003)
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Partner Treatment

• 2 group randomized design
• Control-- receive weekly support group
• Intervention --
• Methadone or detox aftercare
• MI type counseling
• abstinent contingent vouchers
• 1, 3, and 6 month follow-up interviews

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Partner Results

• 35 years old
• 73 unemployed
• 59 African-American
• 72 used cocaine
• 94 believed they were the father of the baby

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Intervention Increases Drug Abstinence in Male
Partners

p 36
Intervention Increases Drug Abstinence in Women

p 37
Intervention Increases Partner Support of the
Woman

p 38
Conclusions

• Interventions are available to engage and retain
  male partners
• Treating the male partner is associated with
  enhanced treatment outcomes for pregnant
  opioid-dependent women

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Take Home Message

• Pregnancy is area where most certainty is
  desired, but there is often the least data
• More medication options will improve the
  treatment of pregnant women
• Engaging and treating the male drug using
  partners can improve the outcomes of women in
  drug treatment

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Acknowledgements

• Rolley Ed Johnson
• Patients and infants
• NIDA R01 DA12220 and DA13496
• Co-Investigators
• Staff at Center for Addiction and Pregnancy
• Staff at BPRU