drug treatment issues in drug-dependent, pregnant women hendrée e. jones, ph.d. department of...
TRANSCRIPT
Drug Treatment Issues in Drug-Dependent, Pregnant
Women
Drug Treatment Issues in Drug-Dependent, Pregnant
Women
Hendrée E. Jones, Ph.D. Department of Psychiatryand Behavioral Sciences
Johns Hopkins University School of MedicineBaltimore, Maryland
APA May 5, 2004
DisclosureDisclosure
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.
APA May 5, 2004
Presentation GoalsPresentation Goals
Use of medication to treat opioid dependence during pregnancy
Clinical trial of methadone and buprenorphine during pregnancy
Behavioral interventions enhance maternal outcomes
APA May 5, 2004
Studies of Medication During PregnancyStudies of Medication During Pregnancy
Controversial
Some say unethical
Stigma associated with medication treatment for pregnant women is severe
APA May 5, 2004
Goals of Opioid Agonist Treatment Goals of Opioid Agonist Treatment
Cessation of opioid use
Stabilize intrauterine environment
Increased prenatal care compliance
Enhanced pregnancy outcomes
APA May 5, 2004
Methadone is effective during pregnancyMethadone 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
APA May 5, 2004
Neonatal Abstinence Syndrome (NAS)
Neonatal Abstinence Syndrome (NAS)
Neuralgic excitability (hyperactivity, irritability, sleep disturbance)
Gastrointestinal dysfunction
(uncoordinated sucking/swallowing, vomiting)
Autonomic Signs (fever, sweating, nasal stuffiness)
APA May 5, 2004
The NAS of Opioid-Exposed NeonatesThe 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
APA May 5, 2004
BuprenorphineBuprenorphine
A derivative of thebaine
Marketed as Subutex or Suboxone
FullAgonist
FullAntagonist
Heroin
MethadoneMorphine
NaltrexoneNaloxone
Buprenorphine Nalmefene
APA May 5, 2004
BuprenorphineBuprenorphine
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
APA May 5, 2004
Case Reports and Open-Label StudiesCase 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 (median=6)
TOTAL 338 babies
APA May 5, 2004
OutlineOutline
Use of medication to treat opioid dependence during pregnancy
Clinical trial of methadone and buprenorphine during pregnancy
Behavioral interventions enhance mother and child outcomes
APA May 5, 2004
Randomized Controlled StudyRandomized 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
APA May 5, 2004
Setting: Center for Addiction & PregnancySetting: Center for Addiction & Pregnancy
Interdisciplinary Approach – Psychiatry– Obstetrics– Pediatrics – Nursing
APA May 5, 2004
CriteriaCriteria
Inclusion:– 18 - 40 years of age– Gestational age 16 - 30 weeks– Opioid dependent (DSM-IV, SCID I)– Recent opioid use– Opioid positive urine
APA May 5, 2004
CriteriaCriteria 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)
APA May 5, 2004
Primary Outcome Measures InfantPrimary Outcome Measures Infant
Neonatal Abstinence Syndrome
(NAS)
Length of Hospital Stay
(LOS)
APA May 5, 2004
Selected Secondary Outcome MeasuresSelected Secondary Outcome Measures
Maternal
– Days of treatment
– Prenatal care visits
– Illicit drug use
Infant
– Physical birth parameters
APA May 5, 2004
Patient FlowPatient FlowNumber screened
1490
Not Qualify Initially1433
Qualify and sign consent57
Randomized 30
Buprenorphine15
Methadone15
Buprenorphine9
Methadone11
APA May 5, 2004
InductionInduction
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
APA May 5, 2004
Maternal OutcomeDrug Use During PregnancyMaternal OutcomeDrug Use During Pregnancy
% 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
Methadone N=11
Buprenorphine N=9
APA May 5, 2004
% 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
Methadone N=11
Buprenorphine N=9
Maternal CharacteristicsMaternal Characteristics
APA May 5, 2004
Maternal OutcomesMaternal Outcomes
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
MethadoneN=11
BuprenorphineN=9
APA May 5, 2004
% 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
Birth Outcomes Methadone N=11
BuprenorphineN=9 deliveries (10 babies)
* data safety monitoring board recommended removing twin data from these variables
APA May 5, 2004
Limitations of StudyLimitations 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
APA May 5, 2004
ConclusionsConclusions 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
APA May 5, 2004
Bottom LineBottom Line
Both medications have strong support to document safety and efficacy for mother and infant
NAS is only part of the complete risk:benefit ratio
More medication options will improve the treatment of pregnant women
APA May 5, 2004
Issues Pregnant, Drug-Dependent Women Face
Multigenerational
drug use Lack of education Maladaptive behaviors
poor self-control
trust issues Legal Parenting
Unstable housing Victimization and
violence
physical
sexual
emotional Severe stigma Other psychiatric
issues
APA May 5, 2004
Presentation GoalsPresentation Goals
Use of medication to treat opioid dependence during pregnancy
Clinical trial of methadone and buprenorphine during pregnancy
Behavioral Interventions enhance maternal outcomes
APA May 5, 2004
Types of Behavioral Interventions Examined at CAP 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
APA May 5, 2004
Relationships as Barriers to TreatmentRelationships 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)
APA May 5, 2004
Women’s Treatment Retention
52
73
0
20
40
60
80 Drug Using (n=82)Drug Free (n=85)
*•Mean relationship of 4 yrs +
• Drug using partners -less employed - less supportive of woman’s treatment -more legal involvement -more dental and medical needs
* P<0.05; Data adapted from Drug and Alcohol Dependence (2003)
APA May 5, 2004
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
APA May 5, 2004
Partner Results
76.6
0
5.8
86.6
17.6 13.3
0%
20%
40%
60%
80%
100%
Control(n=15)
Intervention(n=17)
DetoxificationMethadoneNo treatment
35 years old 73% unemployed 59% African-American 72% used cocaine 94% believed they
were the father of the baby
APA May 5, 2004
100
64 64 60
100
40
1330
0
20
40
60
80
100
Intake 1 3 6
Control (n=15)Intervention (n=17)
*
*p<.05
Intervention Increases Drug Abstinence in Male Partners
APA May 5, 2004
6553 47 41
67
20 13 130
20
40
60
80
100
Intake 1 3 6
Control (n=15)
Intervention (n=17)
*
*p<.05
Intervention Increases Drug Abstinence in Women
APA May 5, 2004
Intervention Increases Partner Support of the Woman
1925 22 2120
2936
30
0
8
16
24
32
40
48
Intake 1 3 6
Control (n=15)Intervention (n=17)
*p<.05
*
APA May 5, 2004
ConclusionsConclusions
Interventions are available to engage and retain male partners
Treating the male partner is associated with enhanced treatment outcomes for pregnant opioid-dependent women
APA May 5, 2004
Take Home MessageTake 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
APA May 5, 2004
AcknowledgementsAcknowledgements
Rolley “Ed” Johnson Patients and infants NIDA R01 DA12220 and DA13496 Co-Investigators Staff at Center for Addiction and
Pregnancy Staff at BPRU