Download Antidepressants in Pregnancy

‘Antidepressants in Pregnancy:
Where are we now ?
Zachary N. Stowe, MD
Director, Women’s Mental Health Program
Professor of Psychiatry, Pediatrics, and Gynecology &
Obstetrics
University of Arkansas for Medical Sciences
Arkansas Children’s Hospital Research Institute
Life Time Financial Disclosure / Conflict
of Interest - Zachary N. Stowe
• No Non-Academic / External Relationships since June 2008
• Off label uses of Medications will be Discussed
• Federal NIH (current):
 P50-77928 (Stowe) - Perinatal Stress and Gene Influences: Pathways to
Infant Vulnerability (TRCBS)
 MONEAD (Meador) - Neurodevelopmental Effects of ‘in utero’ Exposure to
AEDs
Life Time
• Speakers' bureau
– Eli Lilly and Company; GlaxoSmithKline; Pfizer, Inc; Wyeth-Ayerst
Pharmaceuticals, Inc
• Advisory board
– GlaxoSmithKline, Bristol Myer Squibb
• Faculty Development/Training Advisory Committee
– Wyeth-Ayerst Pharmaceuticals, Inc
• Research/educational grants
– GlaxoSmithKline; Pfizer, Inc; Wyeth-Ayerst Pharmaceuticals, Inc
UAMS Women’s Mental Health Program
• Zachary N. Stowe, MD
• Phyllis Wilkins, LCSW
• Bettina Knight, RN
Research Coordinators/Assistants
• Christian Lynch, MPH
• Natalie Morris, BS
• Elaina Rudkin, BS
Residents/Fellows
• Shona Ray, MD
Administration
• Nadir Ellison
• Jan Waldrip
• Summer Alexander
Internal Collaborators
• Transgenerational Biorepository
(ACHRI)
– Barry Brady, Charlotte Hobbs, Jose
Romero, Richard Frye, Janet Stroment,
Tom Badger, Laura James
• SARA Project
– Hair Eswaran, Pamela Murphy, Curtis
Lowery
External Collaborators – Emory University
• D. Jeffrey Newport, M.D.
Neuropharmacology
• Michael Owens, PhD
Pathology
• James Ritchie, PhD
Psychology
• Patricia Brennan, PhD
• Sherryl Goodman, PhD
• Elaine Walker, PhD
Genetics
• Joseph Cubells, MD, PhD
• Elisabeth Binder, MD, PhD
• Alicia Smith, PhD
• David Rubinow, Samantha Meltzer-Brody
(UNC)
• Lindsay DeVane, PharmD (MUSC)
• Stephen Faraone, PhD (SUNY)
• Catherine Monk, PhD (Columbia)
Antidepressants in Pregnancy –
Learning Objectives
• Attendees will be familiar with the
reproductive safety data for antidepressants.
• Appreciate the impact of maternal mental
illness on pregnancy and child outcome.
• Participants will be exposed to a systematic
approach to the treatment of depression
during pregnancy.
• Case examples will be utilized to demonstrate
key clinical concepts.
Background
• > 4,000,000 deliveries in US annually
• > 50% inadvertent conception
• Maternal Age Increasing
– Longer time to develop illness prior to
pregnancy
• Neuropsychiatric Illnesses in Pregnancy
– >500,000 women annually
– 8 health care databases: 6.6% of
women prescribed AD at some point in
pregnancy (Andrade et al 2007)
 e.g. >250,000 exposed annually
• Uniform support for Breast Feeding
Background
• Antidepressant exposure in pregnancy is
increasing
• Antidepressant discontinuation in pregnancy
is increasing
– e.g. discontinuation
• Definitive conclusions are sparse
– Limited concordance with preclinical
literature
– Methodological variation between studies
Maternal Mental Illness during
Pregnancy and Lactation
Treatment
Mental Illness
RISK / BENEFIT DECISION
Numerous Sources of Information and
Opinions Influencing Treatment Planning
Clinician
Delivery Staff
Patient
Obstetrician
Nursery Staff
Significant Other
Pediatrician
Lactation Cons.
Family Members
Therapist
Pharmacist
Internet
FACT: Everyone has an OPINION
(whether they know anything or not)
Psychopharmacology during Pregnancy
and Lactation – STARTING POINTS
• There is an article out there somewhere that
will support virtually any clinical decision.
– Articles citing adverse effects of
medications get a lot of attention and
press.
• Clinically significant versus statistically
significant
– e.g. an Odds ratio of 2.0 for conditions with
an incidence of 1/1000.
Psychopharmacology during Pregnancy
and Lactation – STARTING POINTS
• “Safe” – controlled studies have failed to
identify adverse effects
• “Relative Safety” – medication exposure is
preferable to adverse effects of illness
• “Safe Use” – understanding the dose ranges
and exposures related to the data
• THERE IS VIRTUALLY NO SAFETY DATA
ON THE USE OF 2 MEDICATIONS
– What we have from the AEDs = not good
Antidepressants in Pregnancy – What
do we know ?
• Risks
– Medical Legal Issues
– Birth Defects
– Obstetrical / Neonatal Complications
– Long Term Development
• Management
– Common issues
Medical / Legal
• TV and Web adds for law suits regarding
exposures in pregnancy
– GSK settled case for cardiac defects
• Non-pharmacological interventions may be
effective
– Psychotherapy
 Cognitive Behavioral Therapy
 Interpersonal Psychotherapy
– Exercise
Medical / Legal
• FACT:
– “adverse effects” get more coverage
• E.g. Risk of PPHN
– Cambers et al 2006
 1,213 infants, retrospective OR > 6.0
 New England Journal of Medicine
– Wilson et al 2011
 11,923 infants, case controlled OR = NA
 American Journal of Perinatology
SSRIs & Neonatal Adaptation
Population Study: British Columbia Linked Health Database
Outcomes
(Means / %)
Outcome
C-Section (%)
CTL
19.0
Outcome
Differences
MDD
No Rx
MDD
Rx
21.0
24.0
CTL vs.
MDD No Rx
MDD No Rx
vs. MDD Rx
MATCHED
MDD No Rx
vs. MDD Rx
1.0, p<.01
3.0, p<.01
-0.9, p<.69
Birth Weight (g)
3453
3429 3397 -24, p<.001
-32, p<.05
CONCLUSION:
Prenatal
[SSRI] exposure
was 10, p<.72
EGA Delivery (wks)
39.2
39.1 38.8 -0.06, p<.001
-0.35, p<.001
-0.14, p<.18
associated
with
an increased
risk of low
birth weight
Preterm Birth (%)
6.5
9.0 0.6, p<.007
2.5, p<.001
0.7, p<.61
and
respiratory5.9distress,
even when maternal
illness
SGA (%)
7.4
8.1
8.5 0.7, p<.005
0.5, p<.51
3.3, p<.02
severity
was accounted
for.
Hospital Stay (days)
2.76
2.88
3.31
0.12, p<.006
0.43, p<.007
0.05, p<.83
Resp. Distress (%)
7.4
7.8
13.9
0.04, p<.07
6.3, p<.001
4.4, p<.006
Feeding Probs. (%)
2.1
2.4
3.9
0.03, p<.02
1.5, p<.002
1.1, p<.28
Jaundice (%)
7.9
7.5
9.4
-0.4, p<.08
1.9, p<.01
1.0, p<.45
0.11
0.09
0.14
-0.02, p<.49
0.05, p<.64
0.008, p<.30
Convulsions (%)
(n=119,547)
16
MDD
SSRI
Oberlander TF et al. Arch Gen Psychiatry 2006; 63: 898-906
FDA Pregnancy Categories
Category
Interpretation
A
Controlled studies show no risk: adequate, well-controlled studies
in pregnant women have failed to demonstrate risk to the fetus
B
No evidence of risk in humans: either animal findings show risk,
but human findings do not; or, if no adequate human studies have
been done, animal findings are negative
C
Risk cannot be ruled out: human studies are lacking, and animal
studies are either positive for fetal risk or lacking as well.
However, potential benefits may justify the potential risk
D
Positive evidence of risk: investigational or postmarketing data
show risk to the fetus. Nevertheless, potential benefits may
outweigh risks
X
Contraindicated in pregnancy: studies in animals or humans, or
investigational or postmarketing reports, have shown fetal risk that
clearly outweighs any possible benefit to the patient
Distribution of FDA Category for
Medication Use in Pregnancy
Andrade et al., 2004)
FDA Categories
• The current FDA pregnancy labels are based on
the available knowledge regarding the use of
medications in humans and animals during
pregnancy. The FDA has proposed a new and
more clinical friendly system that includes
information regarding the risks, available data, and
clinical considerations regarding the use of
medications in pregnancy.
• The change was initially discussed in 2006, and it
is unclear if they plan for any ‘retro’ classifying of
approved medications .
Perception of risk
(pre-counseling) *
87% of depressed women
rated risk of antidepressants
as greater than 1–3%
Perception of risk
(post-counseling)
12% of depressed
P value
<0.001
women rated risk of
antidepressants as
greater than 1–3%
56% of women with
gastric problems rated
risk of medications
as greater than 1–3%
4% of women with
gastric problems rated
risk of medications
as greater than 1–3%
<0.001
22% of women with
infections rated the
risk of medications
greater than 1–3%
2% of women with
infections rated the
risk of medications
greater than 1–3%
<0.001
*Actual baseline rate for major malformations in the general population is 1-3
%
Medical / Legal
• It is a laudable goal to avoid AD during
pregnancy
– Other treatments not routinely available
 Therapy $ > Medication Management $
“to be effective, a treatment must be available
and affordable”
Antidepressants in Pregnancy – What
do we know ?
• Risks
– Medical Legal Issues
– Birth Defects
– Obstetrical / Neonatal Complications
– Long Term Development
• Management
– Common issues
SSRIs and NEJM –
• Alwan et al, 2007
– N = 9622 with major birth defects
– N = 4062 without birth defects
– No overall congenital heart defects
– As a group, increased risk of
 Anencephaly (OR 2.4)
– Baseline rate 20:100,000
 Craniosynostosis (OR 2.5)
– Baseline rate 5:10,000
 Omphalocele (OR 2.8)
– Baseline rate 1:10,000
SSRIs and NEJM
• Louik et al, 2007
– N = 9849 infants with birth defects
– N = 5860 infants without birth defects
– No overall birth defects for SSRIs as a
group
– Sertraline
 omphalocele (OR 5.7)
 Septal defects (OR 2.0)
– Paroxetine
 Right ventricular outflow tract
obstruction defects (OR 3.3)
Pedersen et al 2009 BMJ
• n = 493,113
• SSRIs overall increase risk of septal defects
(OR 1.99)
– Sertraline 3.25
– Citalopram 2.52
– Fluoxetine 1.34
– Multiple SSRIs 4.70
• Risk increases 0.5% to 0.9%
AD and Risk for Major Malformations –
Summary
• There are a myriad of studies.
• There is NO consistent pattern of AD
associated birth defects.
• Septal defects reports
– ? Clinical signficance
– Role of prostaglandins
Antidepressants in Pregnancy – What
do we know ?
• Risks
– Medical Legal Issues
– Birth Defects
– Obstetrical / Neonatal Complications
– Long Term Development
• Management
– Common issues
Risk of Gestational HTN with
SSRIs
• Toh et al 2009 AJP
– n = 5731 registry women without known
HTN and with healthy babies
– Increased risk of HTN with SSRIs overall
 9% vs 19.1 %
– Increased risk of HTN with SSRIs after the
first trimester
 13.1% vs. 26.1%
– Increased risk of preeclampsia
 2.4% vs. 3.7% vs. 15.2%
Antidepressant Neonatal Toxicity,
Withdrawal, Abstinence Syndrome
• Original Report in 1973 (Webster 1973)
• Increased attention (Stiskal 2001; Laine 2003; Kallen 2004;
FDA 2004; Sanz 2005, JAMA 2005, 2006)
–
–
–
–
All data derived from cross sectional assessments
Infant evaluator not blind to maternal medication
Highly variable time of symptoms – birth to several days
Symptoms range from CONFUSION to CONVULSIONS
• Withdrawal physiologically unlikely
– Fetal Dosing to point of delivery via umbilical cord
• Warrants further attention, with some degree of
scientific methodology
The 2004 FDA and Health Canada Labeling Change:
Neonatal Withdrawal Syndromes
Nonteratogenic Effects — Neonates exposed to SSRIs or serotonin and norepinephrine
reuptake inhibitors (SNRIs), late in the third trimester have developed complications
requiring
“prolonged
hospitalization, respiratory support, and tube feeding.
Such complications can arise immediately upon delivery.
Reported clinical findings have included respiratory distress,
cyanosis, apnea, seizures, temperature instability, feeding
difficulty, vomiting, hypoglycemia, hypotonia, hypertonia,
hyperreflexia, tremor, jitteriness, irritability, and constant crying”.
These features are consistent with either a direct toxic effect of SSRIs and SNRIs or,
possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the
clinical picture is consistent with serotonin syndrome (see Monoamine oxidase inhibitors
under CONTRAINDICATIONS). When treating a pregnant woman with SSRIs/SNRIs during
the third trimester, the physician should carefully consider the potential risks and benefits of
treatment.
Medication Management Proximate
to Delivery
• Several have suggesting reducing the
dose of antidepressants prior to delivery
to reduce risk of neonatal symptoms
“reduce the medication that the baby has
already been exposed to prior to the
highest risk for psychiatric illness in a
woman’s life to avoid potential transient
symptoms reported for 35 years ?
Persistent Pulmonary Hypertension
(PPHN) and SSRI Exposure
• Chambers CD et al 2006
– 377 PPHN matched with 836 controls
 SSRI Exposure after 20 weeks gestation
 Odds ratio 5.1
• Kallen et al 2008
– 506 PPHN, 831,324 controls
 SSRI Exposure
 Odds Ratio 2.2
• Andrade et al 2009
– WHO Registry
 Odds Ratio 1.4
Study
Description
Women or
Infants in Study
Infants With
PPHN
SSRI Exposure Estimated
Strengths
Risk
Weaknesses
Negative
findings
Andrade et al. Multicenter retrospective 2,208 infants; 1:1 ratio of
third-trimester SSRI(2009)
cohort study
exposed and nonexposed
N=5; two SSRI- No association
exposed
Prospectively
collected exposure
data
Underpowered to detect small
effects
Wichman et
al. (2009)
Retrospective cohort
study
25,214 infants; 2.3% SSRI- N=16; 0 SSRIexposed
exposed
No association
Prospectively
Small SSRI-exposed sample;
collected information underpowered to detect small
effects
Wilson et al.
(2011)
Case-control study;
PPHN identified via echo
or difference in pre- and
postductal oxygen
saturation
11,923 infants; 1:6 ratio of
PPHN patients and healthy
infants; number of SSRIexposed not reported
N=20; 0 SSRIexposed
No association
Explicit diagnostic
criteria for PPHN;
prospectively
captured prescription
information
Incidence of SSRI use in
population unreported; no
control for length of gestation
beyond exclusion of <34
weeks
Exposures based on telephone
interviews with only 70%
participation (potential recall
bias); no control for mode of
delivery or gestational age
beyond 34-week exclusion;
overly sensitive criteria for
PPHN (required PaO2 gradient
of only 5 mm Hg between
pre- and postductal
circulation); not all PPHN
cases confirmed via
echocardiography
Positive
findings
Chambers et
al. (2006)
Multicenter case-control 1,213 infants; 1:2 ratio of
PPHN patients and healthy
study
infants; 3% SSRI-exposed
N=377; 16
SSRI-exposed
Odds ratio=6.1 (95%
CI=2.2–16.8)
Large number of
PPHN cases; required
exposure after 20
weeks
Källén and
Olausson
(2008)
Population-based
831,324 infants; 0.9%
SSRI-exposed
retrospective cohort
study; same data set as
Reis and Källén (2010),
with a shorter time
frame
N=506; 11
SSRI-exposed
Relative risk=3.57 (95%
CI=1.2–8.3)
Large data set;
Cases defined by ICD-9
prospectively
coding alone; no control for
obtained SSRI usage mode of delivery or for
gestational age beyond
exclusion of infants <34
weeks
N=572; 32
SSRI-exposed
In early pregnancy, relative
risk=2.4 (95% CI=1.29–
3.80); in later exposure,
relative risk=2.56 (95%
CI=1.17–4.85); in both
early and late exposure,
relative risk=3.44 (95%
CI=1.49–6.79)
See Källén and
Olausson (2008)
Reis and
Extended version of
Källén (2010) Källén and Olausson
study (2008)
1,251,070 infants; 1.2%
SSRI-exposed
Obstetrical and Neonatal Complications
– Summary
• One are of concordance between the
preclinical and clinical literature is the
increased risk for “respiratory problems”
(broadly defined).
• Patient education – 10-15% of infants will
show transient symptoms in the early
neonatal period.
• In women with history of HTN – venlafaxine
and paroxetine would NOT be preferred
options.
Antidepressants in Pregnancy – What
do we know ?
• Risks
– Medical Legal Issues
– Birth Defects
– Obstetrical / Neonatal Complications
– Long Term Development
• Management
– Common issues
Long-term Impact of Antidepressant (AD) Exposure in Pregnancy
Reference
Design
Age
Sample
Measures
Results
Prospective
16-86
months
Fluoxetine (n=63)
TCA (n=80)
Healthy (n=84)
Bayley, McCarthy,
CBCL, Reynell
No adverse
AD impact
Nulman et al
2002
Prospective
15-71
months
Fluoxetine (n=46)
TCA (n=40)
Healthy (n=36)
Bayley, McCarthy,
CBCL, Reynell
No adverse
AD impact
Mattson et al
1999
Crosssectional
48-60
months
Simon et al
2002
Retrospective
0-24
months
SSRI (n=185)
TCA (n=209)
Medical Records
No adverse
AD impact
Heikkinen et
al 2002
Prospective
12
months
Citalopram (n=11)
Healthy (n=10)
Non-structured
Interview, Medical
Records
No adverse
AD impact
Casper et al
2003
Crosssectional
6-40
months
SSRI (n=31)
MDD & no AD
(n=13)
Bayley
Decreased
psychomotor
Reebye et al
2002
Prospective
3&8
months
Affect Expression
Decreased
Oberlander
et al 2004
Prospective
4&8
months
Bayley
No adverse
AD impact
Misri et al
2006
Prospective
48-60
months
Internalizing Behaviors,
Teacher Report, CBCL
No adverse
AD impact
Oberlander
et al 2007
Prospective
48-60
months
Externalizing &
Attentional Behaviors,
CBCL, IQ
↑aggression
subscores
Nulman et al
1997
No adverse
AD impact
SSRI (n=28)
SSRI+clonazepam
(n=18)
Healthy (n=23)
SSRI (n=13)
SSRI+clonazepam
(n=9)
Healthy (n=14)
Comment
18 Fluoxetine
and 36 TCA
used in both
studies
Teratology 1999
(abstract)
Some enrolled
after delivery
Same Cohort of
Children
Key: Bayley=Bayley Developmental Scales, CBCL=Child Behavior checklist, IQ = Weschler IQ, McCarthy=McCarthy Scales,
Reynell = Reynell Developmental Language Scales
Antidepressants in Pregnancy Long
Term Follow Up – Summary
• Overall limited data.
• No evidence of risk.
• Recent studies suggesting increased risk for
autism spectrum disorder.
– Inconclusive at present
Antidepressants in Pregnancy Keeping
Perspective –
• The extant literature on AD exposure in
pregnancy includes:
– Teratogenic investgations
– Uterine blood flow and fetal activity
– Obstetrical outcome
– Neonatal outcomes
– Limited but present long term follow up data
• By comparison, AD use in pregnancy has been
better scrutinized than most, if not all, other
classes of medication.
Antenatal Maternal Depression: Acute
Maternal & Neonatal Consequences
•
•
Preterm labor
•
Self medication with
drugs, EtOH, and tobacco
Premature birth (<37
weeks)
•
Low birth weight
– 10-12% use tobacco
•
Small for gestational age,
smaller head circumference
– 3% use illicit drugs
•
Low APGAR scores
•
Not bonding with baby
•
Neonatal Complications
•
Effects on family
•
Admission to NICU
•
Suicide
•
Fetal demise
•
Postpartum Depression
•
Non-compliance with
prenatal care
– 14-15% use EtOH
Allister L, et al Neuropsychol 2001;20(3):639-651.
Steer RA, et al J Clin Epidemiol 1992;45(10):1093-1099.
Larsson C, et al Amer. Obstet Gynecol 2004;104:459466.
Chung TKH, et al Psychosom Med 2001;63:830-834.
Rahman A, et al Arch Gen Psychiatry 2004;61:946-952.
Field T, et al Infant Beh Dev 2001;24:27-39.
Hoffman S, Hatch MC. Health Psychol 2000;19(6):535-543.
Orr ST, James SA, Prince CB. Am J Epidemiol 2002;156:797-802.
Zuckerman B, et al Am J Obstet Gynecol 1989;160(5, Part 1):11071111.
Berle JO, et al. Arch Women's Mental Health 2005; 8:181-189
Maternal Depression during the Postpartum
Period and Extended Follow Up
• Elevated Cortisol and Attention Deficits
(Essex et al Biological Psychiatry 2002)
• Increased Violence in 10,11,12 years old (J.
Affect. Disorders 2003)
• Maternal Depression in Pregnancy and
Postpartum predicts higher rates of Conduct
Disorder and Violent Behavior (Arch Gen
Psych 2005)
Maternal Mental Illnesses during
Pregnancy
IMPROVE
WORSENS
+/- CHANGE
•
Eating Disorders
•
•
Depression
•
Mild/Modest
Substance Abuse
•
Bipolar Disorder
•
Psychotic Disorders
+/- Panic Disorder
•
PTSD
•
OCD
Maternal Mental Illnesses during the
Postpartum Period
IMPROVE
WORSENS
+/- CHANGE
•
•
OCD
•
Depression
•
Bipolar Disorder
•
PTSD
•
Psychotic Disorders
•
+/- Eating Disorders
Mild Substance
Abuse
Antidepressants in Pregnancy – What
do we know ?
• Risks
– Medical Legal Issues
– Birth Defects
– Obstetrical / Neonatal Complications
– Long Term Development
• Management
– Common issues
Psychopharmacology during Pregnancy
and Lactation – Common Situations
• Inadvertent conception on medication
• Conceived on medication and patient has
already discontinued
• Psychiatrically stable and approaching
delivery and wants to breast feed
• Symptom worsening during pregnancy and/or
breast feeding
• Pre-conception counseling
Conception on Medications
• “do not panic”
• Exposure has already occurred, and probably
continues through out the bulk of organogenesis
• Start Pre-Natal Vitamin
– 4 mg of folic acid for AEDs
• Reduce Other Risk Factors
– Nicotine
– Alcohol, Drugs of Abuse
– Over the Counter Rx
Human Brain Growth During Gestation
• Most structural organization
in the human brain has
occurred by the end (9 wks
gestation).
• There is marked brain
growth at the end of the
second trimester.
• Maximal acceleration of
weight gain during this time
occurs at 24 weeks
gestation, just at the fringe
of viability ex utero.
• At the end of gestation the
rate of brain growth is
maximal.
• Most of this increase in
growth is related glial cell
formation and new
myelination.
Some Decisions are Worse than Others
Survival Curve for Women with Major Depression
Taking Antidepressants Proximate to Conception
1.0
Maintained Rx (n = 104)
Discounted Rx (n = 103)
0.9
0.8
0.7
0.6
Proportion of
Women Remaining 0.5
Euthymic
0.4
0.3
0.2
0.1
0.0
0
4
8
12
16
20
24
Weeks of Gestation
Cohen LS, et al. JAMA (2006) - Collaborative Study (RO1).
28
32
36
40
Extension of In Utero Data to
Lactation
• Dose in pregnancy >>> Dose in lactation
– Magnitudes of order different dosing
– Blood to Blood versus BM to GI to
blood
• Loss of maternal metabolic support
– Most antidepressant metabolic
pathways are near maturity at term
– Pre-mature raises additional issues
• Developmental different periods
Lactation Safety Classification Schemes
•
•
American Academy of Pediatrics
•
Usually compatible with breastfeeding
•
Unknown but of concern
•
Assoc’d with significant side effects & should be used with caution
•
Requires cessation of breastfeeding
Thomas Hale, Medications and Mothers’ Milk
•
L1 - SAFEST
•
L2 - SAFER
•
L3 – MODERATELY SAFE
•
L4 – POSSIBLY HAZARDOUS
•
L5 – CONTRAINDICATED
Lactation: Comparing the Data & the Safety Ratings
Drug
Exposed
Infants
(N)
Hale Rating
American Academy of Pediatrics Rating
Fluoxetine
202
L3/L2
Unknown but of concern
Sertraline
180
L2
Unknown but of concern
Paroxetine
105
L2
Unknown but of concern
Citalopram
69
L3
Unknown but of concern
143
L2
Usually compatible with breastfeeding
Valproate
Lamotrigine
41
42
L2
L3
Usually compatible with breastfeeding
Unknown but of concern
Lithium
32
L4
Significant side effects; should be given
with caution
Olanzapine
16
L2
Risperidone
3
L3
Quetiapine
1
L4
Carbamazepine
Limited Scientific Evidence to Guide Clinical Decisions
Psychotropic Medication during
Pregnancy and Lactation – Clinical Tips
• Treat all women like they are pregnant from the first
visit.
• “New and Improved = No Data”
• Keep fetal/infant exposures at a minimum (e.g. not
the dose, but total number of medications)
– Limited data on two medications either in series or
combination
– Optimally – single medication exposure
 Conceive on Med A – use Med A
 Pregnancy with Med A – BF Med A
 Switching enters realm of ‘unknown’
Psychotropic Medication during
Pregnancy and Lactation – Clinical Tips
• Baby is not exposed to maternal dose – they
are exposed to maternal blood concentration
in pregnancy (breast milk during lactation).
– Dose adjustments in Pregnancy may be
warranted
– If you are going to take a Rx – you take
enough for it to work
 Minimizing below effective dose simply
exposes to both illness and medication
Negative
Yes
Screen for DEPRESSION
Risk Factors for Depression
Document risk factors and
continue to monitor for
depression
Medical Work Up – CBC,
CMP, TSH, RPR, UDS
No
+ Urine Drug Screen
(Refer to ANGELS Guideline for
+Nicotine Use
1.
2.
3.
Yes
History of previous
treatment for depression?
Prior Treatment
Effective ?
No
Evaluate reproductive
safety information of
prior treatment.
Risk/ Benefit
Assessment for prior
treatment.
Initiation of prior
treatment if indicated
and available.
(Refer to Treatment Tips in
Section II)
Treat as
Indicated, and reevaluate for
depression
Encourage Social Support and Healthy
Behaviors:
1. Compliance with Prenatal Care
2. PNV and/or Folic Acid
3. Adequate Rest/Sleep
4. Appropriate Exercise/Activity
5. Decrease Nicotine, Alcohol, OTC Use
Illicit Substance Abuse)
(Refer to ANGELS Guideline for
Nicotine Dependence)
Yes
Positive
Yes
Is patient willing to Accept
treatment for depression ?
No
Document education about
depression, and continue to
monitor
“Effective Treatment = Relative Safety + Available + Affordable”
Electroconvulsive
Therapy (ECT)
-Safe in pregnancy
-Use in severe
cases or Rx failures
-Limited
availability
Factors to consider in treatment
selection:
1. Appropriate for current
symptoms
2. Reproductive safety data
3. Data in breast feeding
4. Affordability/Health Care
Coverage
Non-Pharmacological
-relaxation, stress reduction, meditation
-Supportive psychotherapy
-Interpersonal psychotherapy (IPT)
-Cognitive Behavioral Therapy (CBT)
-Couples Therapy
-Bright Light Therapy
-Transcranial Magnetic Stimulation
(TMS)
Pharmacological
-SSRIs, SNRIs, TCAs
(Refer to Treatment Tips
in Section II)
Follow up every 2-4 weeks, for medications adjust dose as needed based on response and side effects
Antidepressants in Peripartum
Relative Data
Medication
Pregnancy
Lactation
Dosing Strategies
Comments
Citalopram
(Celexa)
+++
++
Start on 5-10 mg x 2-4 days, then
increase.
Range 10-40 mg/day
Escitalopram
(Lexapro)
+
+
Start on 5 mg x 2-3 days, then
increase.
Range 10-30 mg/day
Fluoxetine
(Prozac, Sarafem)
++++
+++
Start on 10 mg x 4 days, then
increase.
Range 10-60 mg/day
Sertraline
(Zoloft)
+++
++++
Start 25 mg x 2-4 days, then
increase.
Range 25-200 mg/day
Venlafaxine
(Effexor)
++
++
Start on 37.5 mg x 4-7 days, then
increase.
Range 75-225 mg/day
Bupropion
(Welbutrin, Zyban)
++
+
Start on 100 mg SR or 150 mg XL x
7 days, then increase
Range 150-450 mg/day
May also be helpful
in reducing
tobacco use.
Nortriptyline
(Pamelar, Aventyl)
++
++
Start on 10 mg, then increase by
10mg/4 days to 40-50 mg.
Range 30-100 mg/day
May be helpful
with sleep, h/a,
and pain.
20 mg tablet on $4
list
20 mg capsule on
$4 list
Psychotropic Medications in Pregnancy
and Lactation
• Antidepressants
• Mood Stabilizers
• Antipsychotics
• Benzodiazepines
• Stimulants
Summary
• Treat all women of reproductive years as if they were
pregnant from the first visit.
• All medications cross the placenta and enter human breast
milk.
• Large data base on psychotropic medications.
– Limitations preclude definitive conclusions, except for
AEDs
• Strong evidence that untreated maternal depression during
pregnancy and the postpartum period has adverse impact
on offspring.
• Postnatal environment is extremely important, and may
serve to modulate medication effects.
So I Hope this Clears Things Up
If I can be of help
• [email protected]
• Office – (501) 526-8201
• Cell – (678) 640-0470