Pharmacological Treatment of Opioid Dependence during Pregnancy: Methadone and Buprenorphine

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Pharmacological Treatment of Opioid Dependence
during Pregnancy Methadone and Buprenorphine

• Overview
• Karol Kaltenbach, PhD
• Maternal Addiction Treatment Education and
  Research
• Thomas Jefferson University

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Pharmacological Management

• Methadone Maintenance has been recommended for
  opioid dependent pregnant women since the early
  1970s
• 1997 NIH Consensus Panel recommended as standard
  of care

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Methadone Maintenance and Pregnancy

• Effective methadone maintenance
• Prevents the onset of withdrawal for 24 hours
• Reduces or eliminates drug craving
• Blocks the euphoric effects of other narcotics

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Methadone Maintenance and Pregnancy

• In addition, during pregnancy methadone
  maintenance
• Prevents erratic maternal opioid levels and
  protects the fetus from repeated episodes of
  withdrawal
• Decreases risks to fetus of infection from HIV,
  hepatitis and sexually transmitted disease
• Reduces the incidence of obstetrical and fetal
  complications

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Issues in Methadone and Pregnancy Historical and
Contemporary

• Appropriate dose during pregnancy
• Severity of neonatal abstinence related to
  maternal dose

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Issues of Dose During Pregnancy

• Previous FDA regulations required the lowest
  effective dose
• Dose should be based on the same criteria used
  for non-pregnant patients
• Original work by Dole and Nyswander suggests that
  effective dose is usually in the range of
  80-120mg
• Current consensus is 50-150mg, with blood plasma
  levels 200ng/ml

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Issues of Dose During Pregnancy

• In the late 1970s recommendations emerged for
  pregnant women to be maintained on low dose,
  i.e.lt 20mg
• Such low dose recommendations are based on
  attempts to reduce or eliminate neonatal
  abstinence and are contrary to the therapeutic
  objectives of methadone maintenance

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Dose and Blood Plasma Levels

• Subjects N45 pregnant women
• Six stabilized on methadone before they
• became pregnant.
• Thirty-nine were pregnant at the time of
• their admit for stabilization
• Age x28yrs (19-40 yrs)
• Methadone dose x112 mg (35-215mg)
• Gestational age x26wks (10-38 wks)
• Drozdick et al, Am J Obstet Gynecol Vol.187, No
  5, 2002

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Dose and Blood Plasma Levels

• Results
• 20 women had trough plasma levels in the
  therapeutic range of gt200ng/ml
• Methadone dose x128mg (80-190mg)
• Trough level x310ng/ml
• Negative UDS 83

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Dose and Blood Plasma Levels

• Results
• 25 women had trough plasma levels
• lt 200ng/ml
• Methadone dose x98.6 (35-215mg)
• Trough plasma level x118ng/ml
• Negative UDS x40

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Dose and Blood Plasma Levels

• Summary of findings
• The need for some pregnant women to be maintained
  on higher doses (gt80mg) to be at a therapeutic
  level
• The idiosyncratic variability of adequate dose
• The importance of measuring methadone serum
  levels in making dosing decisions for pregnant
  women

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Neonatal Abstinence

• Infants prenatally exposed to heroin or methadone
  have a high incidence of neonatal abstinence
• Neonatal abstinence (NAS) may be more severe
  and/or prolonged with methadone than heroin
• Research indicates that 60-87 of infants born to
  methadone maintained mothers require treatment
  for NAS

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Issues Regarding Relationship of Maternal Dose
and Neonatal Abstinence

• Continued debate regarding relationship between
  maternal dose and NAS
• Often recommended to reduce maternal methadone
  dose to avoid neonatal abstinence
• A non-therapeutic maternal dose may promote
  supplemental drug use and increase risk to the
  fetus

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No Relationship between NAS and Maternal Dose
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Methadone Dose and Neonatal Withdrawal

• Mean Dose N NWT LOS
• lt20 mg 25 3 7
• 20-39 mg 20 11 15
• gt40 mg 20
  18 38
• Dashe et al. Am J of Obstet Gynecol, 2002

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Methadone Dose and Neonatal Withdrawal

• Mean dose N Mean birth-weight NWT
  LOS
• lt80mg 50 2769/-559
  34 (68) 13.3
• gt80mg 50 2663/-556
  33 (66) 13.6
• Last dose N Mean birth-weight NWT
  LOS
• lt80mg 39 2811/-586
  29 (74) 14.2
• gt80mg 61 2655/-534
  38 (62) 12.9
• Berghella et al. Am J Obstet Gynecol, 2003

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Methadone Dose and Neonatal Withdrawal

• Benzo N Highest NAS NWT LOS
• Negative 61 10.1/-4.4 37(61)
  9.6/-11.5
• Positive 39 13.3/-12.8
  30(77) 19.5/-26.3
• p.08
  p.09 p.01

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Impact of Buprenorphine

• May be effective treatment alternative for some
  women
• Women who dont want to be maintained on
  methadone
• Women who live in areas where methadone is not
  available
• Women for whom methadone program compliance is
  difficult

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Buprenorphine and NAS

• Buprenorphine may produce a NAS that is milder
  and of shorter duration than methadone.
• However, need to insure that history is not
  repeated and that pharmacotherapy decisions are
  based on therapeutic objectives of treatment.
• Buprenorphine should not be the treatment of
  choice solely on the basis of reducing symptoms
  of NAS.

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Methadone and Buprenorphine

• Will increase treatment options for women
• Will increase effectiveness of treatment
• IF
• We recognize that one size does not fit all
• And pharmacotherapy decisions are based on
  effective treatment