Transcript Trends, Treatments and Outcomes of Opioid Use in Pregnancy

Trends, treatment and outcomes of
opioid use disorders in pregnancy
Mishka Terplan MD MPH FACOG
Diplomate ABAM
Medical Director
Behavioral Health System Baltimore
Diclosures
• I have no commercial interests or financial
involvements with pharmaceutical or similar
companies
• I do receive some funding from DHMH
• Discussing 2 medications, methadone and
buprenorphine. Neither medication is approved for use
in pregnant women. Both labeled by FDA as Category C
for use in pregnancy:
– “Animal reproduction studies have shown an adverse
effect on the fetus and there are no adequate and wellcontrolled studies in humans, but potential benefits may
warrant use of the drug in pregnant women despite
potential risks.”
Objectives
• 1) to review trends in opioid use in general
and in pregnancy in particular
• 2) to discuss the natural history of substance
use in pregnancy
• 3) to discuss the treatment of opioid use
disorders in pregnancy (including screening)
• 4) to discuss outcomes of both opioid use and
opioid treatment during pregnancy
Opioids Trends
Rates of opioid pain reliever (OPR) overdose death, OPR treatment
admissions, and kilograms of OPR sold --- United States, 1999--2010
MMWR 11/4/11
* Age-adjusted rates per 100,000 population for OPR deaths, crude rates per 10,000 population for
OPR abuse treatment admissions, and crude rates per 10,000 population for kilograms of OPR sold.
Overdose in the US
Treatment for Opioid Use Disorders in
Pregnancy
Martin et al JSAT 2014
Martin et al JSAT 2014
Patrick SW, JAMA,
2012
Eugene Grasset, La Morphinomane, 1897 color lithograph
Historical Context
• Harrison Narcotic Act of 1914 - required that addictive
substances needed to be prescribed by a licensed health
professional
• Result: Substance use and addiction defined as criminal not
public health problem
• Women unable to stop using substances were forced to
seek them from illegitimate sources
• Some enlightened physicians treated opioid addiction with
morphine - In 1919, this practice was prohibited by the
Supreme Court
• Result: Segregation of the treatment of substance use
disorders from general medical practice
Pregnancy and Substance Use Today
No bystander
could be more
innocent. No
damage so
helplessly
collateral.
WaPo 1989
Stigma
• Pregnant women who use drugs endure a
particular “stigma”
• Pregnant women are treated differently by the
CJ system
• Stigma is euphemism
• More appropriate terms:
– Discrimination or Prejudice
Why are pregnant women who use
drugs discriminated against?
• Combination of
– specific state-level policies coupled with the
– (failed) drug war policies
Punishing pregnant women: not best
practice
• Unnatural
– Maternal-fetal unit, maternal-infant dyad - Policies
in effect cleave this unit
– Historically the mother has been seen as advocate
for pregnancy
• Discriminatory in how applied
– Although SUDs affect all, white women more likely
to use in pregnancy, black women and poor
women far more likely to be arrested, prosecuted,
portrayed in media, etc.
Punishing pregnant women: not best
practice
• Not grounded in evidence
– Harms of illicit substances exaggerated; effects of
licit substances minimized
• Unintended consequences
– Does not improve health outcomes for mothers
and babies
– Disincentive to seek prenatal care or SUD
treatment
– Treatment works; PNC ameliorates adverse effects
among substances in using women
Best practices: Language is important
“Once I had a life in
my hands, I didn’t
want to screw it up”
Terminology
• Terms I use:
• Terms I avoid:
– Substance Use
– Substance Abuse
– Substance Use
Disorder
– Addict
– Addiction
• In between terms:
– Tolerance
– Dependence
What happens when women who use
substances get pregnant?
The Natural History of Substance Use in
Pregnancy: An Example of Self-Change
Does substance use change through
course of pregnancy?
Substance use by trimester
Pregnant
Not pregnant
Alcohol
First
Second
Third
19.0
5.0
4.4
9.4
54.0
Cigarettes
First
Second
Third
19.9
13.4
12.8
15.4
24.0
Illicit drugs
First
Second
Third
9.0
4.8
2.4
5.4
11.4
NSDUH 2012/13
Past month
Comparing pregnant and nonpregnant adolescents
Salas-Wright Addic
Behav 2015
What about postpartum?
Ebrahim et al (AJOG 2003)
What happens when women who use
substances get pregnant?
• Compared to non-pregnant women, women
drink less alcohol, smoke fewer cigarettes, and
use fewer illicit drugs during pregnancy
• Use decreases through the course of
pregnancy by trimester
• The greatest reduction is seen earlier
• About 80% resume use postpartum
All pregnant women are motivated to
maximize their health and that of their
baby-to-be
• All women are aware of the risks associated
with substance use
• All employ a range of strategies to reduce or
change intake
– Decrease or stop use
– Switch drugs
– Enter prenatal care
– Enter SUD treatment
Those who can’t quit or cut back –
have a substance use disorder
• Continued use in pregnancy is pathognomonic
for addiction
Treatment for SUDs in pregnancy:
National data
Substance
N(%)
Marijuana
Opioids
Heroin
Stimulants
4449 (20.3)
4268 (19.0)
4135 (18.9)
3477 (15.9)
Alcohol
Other
3246 (14.8)
2351 (10.7)
Primary substance TEDS 2012
SUD treatment Baltimore City:
Top 4 substances
1
2
Pregnant (%)
Heroin (75%)
Marijuana (6%)
General population (%)
Heroin (59%)
Alcohol (13%)
3
4
Prescription opioids (5%)
Cocaine (4%)
Marijuana (13%)
Cocaine (10%)
Characteristic
Percent
White
69.7
Unemployed/not in labor force
87.3
No prior arrests
88.4
Education
Less than HS
High School
More than HS
39.9
39.2
20.9
Number of Substances
1
2
3+
37.7
37.0
24.6
IDU
24.1
Psychiatric diagnosis
36.1
TEDS 2012
National-level data are insufficient
• Pregnant women with SUDs
–
–
–
–
–
–
–
Two thirds have childhood trauma
10-50% past year intimate partner violence (IPV)
Higher rates of co-occurring disorders (depression)
Inadequate social supports
Children - unpredictable parenting models
Poor nutrition
High rates of smoking
• Unique set of needs
Principles of treatment: Integration
• Comprehensive and/or co-located services that
address social needs ideal
• Close collaborative relationships between SUD
and PNC providers
• Care for pregnant women with opioid use
disorder should be co-managed by an
obstetrician and an addiction specialist physician
– Consents for information sharing
– Warm/hot handoffs
– Team meetings
Principles of treatment
• Early identification is key
– Early identification of substance use allows for early
intervention and treatment which minimizes potential
harms to the mother and her pregnancy
– Maximize the motivation for change during pregnancy
• Screening
– Screening pregnant women in prenatal care for
substance use
– Screening reproductive aged women in SUD
treatment for pregnancy – pregnancy intention
Screening for Substance Use
• Universal screening (for licit and illicit
substance use) is recommended
– Alcohol (ACOG 2011)
– Prescription opioids (ACOG 2012)
• Selective screening based on “risk factors”
perpetuates discrimination and misses most
women with problematic use
Prenatal Care Screening
Condition
Prevalence
Cystic Fibrosis (Caucasians)
HIV
1/2500 = 0.0004%
1/500 = 0.002%
Birth Defects
2%
Anemia
2-4%
Pre-eclampsia
2-8%
Gestational diabetes
2-10%
Post partum depression
10-15%
Substance Use
Prevalence
Alcohol
9.4%
Cigarettes
15.4%
Illicit drugs
5.4%
Reasons Patients Don’t Disclose
Substance Use
• Fear of discrimination or judgment
• Previous bad experience with health care
provider
• Fear of Child Protective Services
• They don’t consider their use problematic
Screen for substance use and use
disorders in pregnancy
• Patients are usually not offended by questions about
substance use if asked in caring and nonjudgmental manner.
• Normalize questions:
– Embed them in other health behavior questions
– Preface questions by stating that all patients are asked about
substance use
• Ask permission
– “Is it OK if I ask you some questions about smoking, alcohol and
other drugs?”
• Avoid closed-ended questions
– “You don’t smoke or use drugs, do you?”
Screening: Instruments
• There is no single best screening instrument to identify pregnant women
with substance problems
• Instruments can be either self-completed or done as part of the patient
interview
• The following instruments have been developed or validated among
pregnant women (partial list)
– Alcohol
• T-ACE (Sokol 1989)
• TWEAK (Chang 1999)
– Both alcohol and other substance use
• DAST and MAST (Kemper 1993)
• 4P’s Plus (Chasnoff 1999)
• CRAFFT (Chang 2011) for pregnant adolescents
Screening: Urine
• Should not be used as sole assessment of substance problems
(ACOG 2012)
– Short detection window (substance dependent)
– Might not capture binge or intermittent use
– Rarely detects alcohol
– Doesn’t capture prescription opioids (without confirmation testing)
• Mandatory urine testing – unfavorable policy that does not
support healthy pregnancy outcomes (ACOG 2014)
• Useful adjunct primarily for individuals during or after
treatment (ASAM 2010)
• Ethical issues – patient needs to give consent prior to
specimen collection
Screen for reproductive health needs in
SUD treatment
• Women in SUD treatment are at increased risk of sexually
transmitted infections (STIs) especially HIV (Armstrong 1999)
• Women in SUD treatment are at increased risk of unintended
pregnancy
– Higher lifetime parity (Weber 2003)
– Higher unintended pregnancy rates (Heil 2011)
– Higher abortion rates (Martino 2006)
• Women in drug treatment are less likely to use effective
contraception (Black 2012) (Sharpe 2008)
Pregnancy planning is harm reduction
• Screening for reproductive health needs is
important and easy
• Single question:
Would You Like to Become Pregnant in the Next Year?
• Oregon Foundation for Reproductive Health
(www.onekeyquestion.org)
What are the consequences of SUD in
pregnancy?
What are the consequences of SUD in
pregnancy?
Substance
Consequence
Alcohol
Preterm birth, low birth weight
Teratogen: Leading preventable cause of intellectual and
developmental disorders in US
FAS/FASD – alcohol-related neurodevelopmental disorder cognitive and behavioral deficits
Nicotine
Reduced fertility
Miscarriage
Preterm delivery (premature rupture of membranes, placental
abruption, previa)
Low birth weight (reduced fetal growth)
SIDS, respiratory infections
Opioids
NAS
Stimulants
? Low birth weight
Placental abruption (rare)
Marijuana
? Low birth weight
Substance effects are synergistic
Odendaal, Gynecl Obstet Invest 2009
Treatment for Opioid Use Disorders in
Pregnancy
• Standard of care: Medication Assisted Treatment
– Methadone or Buprenorphine – with counseling
• “Because it is crucial that pregnant women engage in
treatment for their addictions, OTPs should give
priority to admitting pregnant patients at any point
during pregnancy and providing them with all
necessary care, including adequate dosing strategies as
well as referrals for prenatal and follow-up postpartum
services.” (Federal Guidelines for Opioid Treatment
Programs, 2015)
• Pregnant women – don’t need to meet DSM criteria for
use disorder to receive MAT (TIP 43)
Medication for opioid use disorders in
pregnancy?
• Methadone standard of care since 1970s
• Buprenorphine studied since 2002
• What about naltrexone?
Methadone – Historical Context
• Developed as analgesic
prior to WW II
• First utilized in US 1940s
for medication-assisted
withdrawal – with relapse
rates >90%
• 1960’s Dole and
Nyswander –
maintenance
• Effective dosing leads to
tolerance and a reduction
or elimination of craving
for heroin
Benefits of MAT in pregnancy
• Stable intrauterine environment (no cyclic
withdrawal)
• Decrease/cessation in illicit drug use - reduction
of HIV/HCV acquisition
• Increased PNC adherence
• Enhanced pregnancy outcomes:
– Increased maternal weight gain
– Increased newborn birth weight and gestational age
• Decrease risk of overdose
• Other supportive services
Methadone
• 80% orally bioavailable – elimination half life
– 24-36 hours
• Body clearance varies considerably between
individuals
• μ opioid receptor agonist
• Only FDA-approved medication during
pregnancy
• Serum methadone levels and elimination
half-life influenced by pregnancy
– Increased fluid volume
– Larger tissue reservoir
– Altered opioid metabolism in both fetus and
placenta – CYP3A induction
Buprenorphine
 μ opioid receptor partial
agonist
 Primarily antagonistic actions
on κ opioid and δopioid
receptors
 Half-life c. 24-60 hours
 Formulations:
 Mono product (Subutex)
 With naloxone (Suboxone) –
4:1 ratio to prevent injection
 2mg and 8mg sublingual
tablets or film strips
67
MOTHER Study:
Primary Outcomes
100
Treated for
NAS
[Yes]
25
NAS peak
score
Total amount of
morphine for
15 NAS (mg)
20
75
10
15
50
• Compared with methadoneexposed neonates,
buprenorphine-exposed
p = .00000012
neonates
10
5
25
5
0
0
0
Days of infant
hospital stay
Head
circumference
50
(cm)
20
15
40
p = .00012
30
10
5
0
■ Methadone
■ Buprenorphine
20
10
– Required 89% less
morphine to treat NAS
– Spent 43% less time in the
hospital
– Spent 58% less time in the
hospital being medicated
for NAS
• Both medications in the
context of comprehensive
care produced similar
maternal treatment and
delivery outcomes
0
Notes: Significant results are encircled. Site was a blocking factor in all analyses. The O’BrienFleming α spending function resulted in α = .0091 for the inferential tests of the Medication
Condition effect for the 5 primary outcome measures at the conclusion of the trial.
67
Jones et al., N Engl J Med. 2010.
68
MOTHER Study:
Secondary Outcomes
Medication dose at
delivery, mg
Drug screen at
delivery [Positive]
Premature
discontinuance [Yes]
50
100
25
Medical
complications at
100 delivery [Yes]
40
20
80
30
15
60
20
10
40
25
10
5
20
0
0
0
0
75
50
■ Methadone
Normal
presentation
[Yes]
100
75
Cesarean section
[Yes]
■ Buprenorphine
Maternal weight
gain, kg
Number of
prenatal
obstetrical visits
50
10
40
8
30
6
6
20
4
4
10
2
2
500
0
0
0
0
10
2000
8
1500
50
25
0
Amount of voucher
Money earned
for drug-negative tests,
US$
Note: Bonferroni’s principle was used to set familywise α =
.003125 (nominal α = .05/16) for the secondary outcome measures.
1000
 Clinically
meaningful
attrition rate in
buprenorphine
condition
 Low rates of
illicit drug use
during
pregnancy
and at delivery
 Maternal
outcomes similar
in the 2 study
conditions
Jones et al., N Engl J Med, 2010.
68
69
MOTHER Study:
Secondary Analysis Studies
Time to Morphine Treatment Initiation
80
p = .01
Hours
60
40
20
0
Methadone
(n = 41)
Buprenorphine
(n = 27)
►
There was a significant
difference between
medication conditions in
mean time to initiation of
morphine treatment for
those neonates treated for
NAS, with the methadone
condition requiring
morphine treatment
earlier than the
buprenorphine condition
Gaalema et al., Addiction, 107 (Suppl. 1), 53–62.
MAT Summary
• Methadone
– May have better
treatment retention
– No risk precipitating
withdrawal
– Patients with high opioid
tolerance
• Buprenorphine
– Probably less severe NAS
– Reduced risk of overdose
during induction
– Reduced risk of overdose
if children exposed to
medication
NAS is an expected and treatable complication of MAT in pregnancy
Treatment for Opioid Use Disorders in
Pregnancy
• How to dose pregnant women?
– Dose increase earlier to avoid fetal withdrawal
– Overlap in symptoms between normal pregnancy and
withdrawal
• Third trimester (often methadone dose needs adjustment
upwards as gestational age increases)
– Physiological changes (metabolism, circulating volume) may
need increase dose
– Consider split dosing
– Individualized treatment – do not automatically increase
• Post partum
– 4-6 weeks for return to pre-pregnancy state
– Individualize decrease – no evidence-base
MAT considerations
• Detox – medically supervised withdrawal – not
recommended however could be individually
considered – (not before 14 weeks or after 32
weeks) (Federal Guidelines for opioid tx 2015)
• Maternal dose reduction (to prevent NAS) not
recommended
• Third trimester automatic methadone dose
increases (without individual evaluation) not
recommended
• Buprenorphine with naltrexone is safe to use in
pregnancy
Treatment for Opioid Use Disorders in
Pregnancy
• Labor and Delivery considerations:
– Dose verification essential (signed releases)
– Maintain maintenance dose (baseline)
– Mode of delivery to be decided by obstetric
indications only
– Regional anesthesia preferred
• Cesarean delivery
• Post operative pain
Neonatal Abstinence Syndrome
• Expected and treatable consequence of opioid
use in pregnancy (ACOG 2012) (GAO 2015)
• Without long term negative outcomes
• 50-90% of opioid-exposed neonates exhibit NAS
• Complex and influenced by: smoking, other
substance use, medications (SSRIs), preterm
delivery, genetics
• No clear relationship between methadone/bupe
dose and NAS
NAS: Other Factors Contributing to
Severity
 Structural
 The NAS assessment
 Medication initiation
 Weaning protocols
 Non-modifiable
 Genetics
 Other Substances
 Benzodiazepines
 SSRIs
 Cigarette smoking
Jansson and Velez,Curr. Opin Pediatrics, 2012
Substance Exposed Newborn
Reporting
• The Child Abuse and Prevention Treatment Act
(CAPTA) Reauthorization Act of 2010 requires
States to have policies and procedures for
hospitals to notify child protective services (CPS)
of all children born who are affected by illegal
substance abuse or withdrawal symptoms
resulting from prenatal drug exposure or
indications of fetal alcohol spectrum disorder.
• Generally speaking – providers over-report
Substance Exposed Newborn
Reporting: Maryland
• Substance use not child abuse
• “Alternative Reporting” mechanism
• Reporting after birth – CPS responds within 72
hours
• Unique resources available for participants
• Baltimore City - c40 newborns/month, 80+%
MJ only
Conclusions
• All pregnant women manifest motivation to maximize their
health during pregnancy
• Most women stop or decrease use in pregnancy
• Those that can’t have a SUD
• Engagement in care improves outcomes
• However pregnant women with SUDs have unique set of
needs and experience discrimination
• Therefore care needs to be compassionate and nonjudgmental, comprehensive and coordinated with PNC
provider
• Preventing substance exposed pregnancies means
decreasing unplanned pregnancies, increasing access to
reproductive health services, specifically contraception
Thank you
• Mishka Terplan
• [email protected]
Resources
• Providers’ Clinical Support System For Medication
Assisted Treatment training modules and
webinars http://pcssmat.org/ (CME available)
• National Center on Substance Abuse and Child
Welfare (NCSACW) “A collaborative approach to
the treatment of pregnant women with opioid
use disorders” https://www.ncsacw.samhsa.gov/
• ASAM National Practice Guidelines for the use of
medications in the treatment of addiction
involving opioid use. 2015
Web-Based Trainings for SBIRT
•
www.smokingcessationandpregnancy.org
‒ Excellent web-based virtual clinic with actual and simulated patients.
‒ $25 access for 1 year. Free for residents.
‒ CDC, Dartmouth, ACOG
•
http://www.naccho.org/toolbox/tool.cfm?id=3215
‒ Developed by ACOG
‒ Free, includes 3 hours CME
•
http://www.thedoctorschannel.com/view/intro-to-motivational-interviewing/
‒ Free CME
•
http://www.sbirttraining.com
‒ Developed by ASAM (American Society for Addiction Medicine)
‒ $50 includes 4 hours CME
References
•
•
•
•
•
Substance Abuse and Mental Health Services Administration. Federal Guidelines
for Opioid Treatment Programs. HHS Publication No. (SMA) PEP15-FEDGUIDEOTP.
Rockville, MD: Substance Abuse and Mental Health Services Administration, 2015
Substance Abuse and Mental Health Services Administration. A Collaborative
Approach to the Treatment of Pregnant Women with Opioid Use Disorders,
Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.
Available at: http://samhsa.gov
GAO-15-203 Prenatal Drug Use and Newborn Health: Federal Efforts Need Better
Planning and Coordination February 2015
Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid
Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP)
Series 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse
and Mental Health Services Administration, 2005
Center for Substance Abuse Treatment. Substance Abuse Treatment: Addressing
the Specific Needs of Women. Treatment Improvement Protocol (TIP) Series, No.
51. HHS Publication No. (SMA) 14-4426. Rockville, MD: Substance Abuse and
Mental Health Services Administration, 2009
References
• American Congress of Obstetricians and
Gynecologists. Pregnant women & prescription
drug abuse, dependence and addiction. Toolkit on
State Legislation. ACOG;2014.
• Committee on Health Care for Underserved
Women, American Society of Addiction Medicine.
ACOG Committee Opinion No. 524: Opioid abuse,
dependence, and addiction in pregnancy. Obstet.
Gynecol. May 2012;119(5):1070-1076.
Policy References
• Young, N. K., Gardner, S., Otero, C., Dennis, K.,
Chang, R., Earle, K., & Amatetti, S.
Substance‐Exposed Infants: State Responses to
the Problem. HHS Pub. No. (SMA) 09‐4369.
Rockville, MD: Substance Abuse and Mental
Health Services Administration, 2009
• Guttmacher Institute. Substance Abuse
During Pregnancy: State Policies in Brief, July
2014