Download - Pharmacological Treatment of Opioid Dependence during Pregnancy: Methadone and Buprenorphine
Pharmacological Treatment of Opioid Dependence during Pregnancy: Methadone and Buprenorphine
OverviewKarol Kaltenbach, PhD
Maternal Addiction Treatment Education and Research
Thomas Jefferson University
Pharmacological Management
Methadone Maintenance has been recommended for opioid dependent pregnant women since the early 1970’s
1997 NIH Consensus Panel recommended as standard of care
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
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
Issues in Methadone and Pregnancy: Historical and Contemporary
Appropriate dose during pregnancy Severity of neonatal abstinence related
to maternal dose
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
Issues of Dose During Pregnancy
In the late 1970’s recommendations emerged for pregnant women to be maintained on low dose, i.e.< 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
Dose and Blood Plasma Levels
Subjects: N=45 pregnant women: Six stabilized on methadone before they became pregnant. Thirty-nine were pregnant at the time of
their admit for stabilization– Age x=28yrs (19-40 yrs)– Methadone dose x=112 mg (35-215mg)– Gestational age x=26wks (10-38 wks)
Drozdick et al, Am J Obstet Gynecol Vol.187, No 5, 2002
Dose and Blood Plasma Levels
Results:20 women had trough plasma levels in the therapeutic range of >200ng/mlMethadone dose x=128mg (80-
190mg)Trough level x=310ng/mlNegative UDS 83%
Dose and Blood Plasma Levels
Results25 women had trough plasma levels
< 200ng/mlMethadone dose x=98.6 (35-215mg)Trough plasma level x=118ng/mlNegative UDS x=40%
Dose and Blood Plasma Levels
Summary of findings– The need for some pregnant women to be
maintained on higher doses (>80mg) 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
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
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
Ostrea et al. 1976 N=95 15mg 23 mg
Madden et al. 1977 N=110 0-20mg >20mg
Harper et al. 1977 N=21 Mean dose =28mg 5-60
Kandall et al. 1983 N=153 50mg 29mg
Suffet et al. 1984 N=216 Mean dose=29mg
Doberczak et al. 1991 N=21 Mean dose=47mg 20-80
Malpas et al. 1995 N=70 Mean dose=15.4mg 0->21
Mayes et al. 1996 N=68 Mean dose=44mg 15-80
Dashe et al. 2002
No Relationship between NAS and Maternal Dose
Blinick et al. 1973 N= 61 80-140 mg
Newman et al. 1974 N=331 40mg-90 mg
Rosen et al. 1976 N=30 Mean dose=38mg 10-100 mg
Stimmel et al. 1982 N=239 <50mg 50mg >50mg
Thakur et al. 1990 N=152 10-40mg 40-60mg >60 mg
10-70 mg
Shaw et al. 1994 N=32 Median dose = 35mg 5-80 mg
Hagopian et al. 1995 N=172 Mean dose = 31mg 10-60 mg
Kaltenbach et al. 1997 N=38 <80mg ≥80 mg 35-135 mg
Brown et al. 1998 N=32 50 mg ≥ 50 mg
Methadone Dose and Neonatal Withdrawal
Mean Dose N NWT LOS <20 mg 25 3 7
20-39 mg 20 11 15
>40 mg 20 18 38
Dashe et al. Am J of Obstet Gynecol, 2002
Methadone Dose and Neonatal Withdrawal
Mean dose N Mean birth-weight NWT LOS
<80mg 50 2769+/-559 34 (68%) 13.3>80mg 50 2663+/-556 33 (66%) 13.6
Last dose N Mean birth-weight NWT LOS
<80mg 39 2811+/-586 29 (74%) 14.2>80mg 61 2655+/-534 38 (62%) 12.9
Berghella et al. Am J Obstet Gynecol, 2003
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
Impact of Buprenorphine
May be effective treatment alternative for some women– Women who don’t want to be
maintained on methadone– Women who live in areas where
methadone is not available– Women for whom methadone
program compliance is difficult
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.
Methadone and Buprenorphine
Will increase treatment options for women Will increase effectiveness of treatment
IFWe recognize that “one size does not fit all”And pharmacotherapy decisions are based
on “effective treatment”