‘Treatment of Depression during
Pregnancy”
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
CDC/NCBDDD - Birth Defects Study to Evaluate Pregnancy exposures
(BD-STEPS) Principal Investigator (Hobbs, C)
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
• Shona Ray, MD
• Bettina Knight, RN
Research Coordinators/Assistants
• Christina Coker, B.S.
• Christian Lynch, MPH
• Natalie Morris, BS
• Elaina Rudkin, BS
Residents/Fellows
• Jessica Coker, M.D.
• Veronica Raney, M.D.
• Samuel House, M.D.
Administration
• Nadir Ellison
• Summer Alexander
Internal Collaborators
• Perinatal Opiate Project
• Transgenerational Biorepository
(ACHRI)
• Fetal MEG/Motor Coupling
External Collaborators –
• D. Jeffrey Newport, M.D. – Univ of Miami
Neuropharmacology
• Michael Owens, PhD – Emory
Pathology
• James Ritchie, PhD – Emory
Psychology
• Patricia Brennan, PhD – Emory
• Sherryl Goodman, PhD – Emory
• Katrina Johnson, PhD – Emory
Genetics
• Joseph Cubells, MD, PhD – Emory
• Elisabeth Binder, MD, PhD – Max Planc
• Alicia Smith, PhD – Emory
•
•
•
•
•
•
David Rubinow, M.D. (UNC)
Samantha Meltzer-Brody , M.D., MPH (UNC)
Lindsay DeVane, PharmD (MUSC)
Stephen Faraone, PhD (SUNY)
Catherine Monk, PhD (Columbia)
Charles Nemeroff, M.D., PhD (Miami)
Audience Response Question
Depression during Pregnancy
• What is your current clinical comfort level with
identifying and treating depression during
pregnancy ?
– A. Not comfortable
– B. Somewhat comfortable
– C. Comfortable
– D. Very comfortable
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
Andrade et al 2007
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 MULTIPLE MEDICATIONS
– What we have from the AEDs = not good
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)
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Antenatal Depression: Prevalence
Kumar R, Robson RM. Br J Psychiatry 1984;144:35-47. Hobfoll SE et al. J Consult Clin Psychol 1995;63:445-453.
Kelly R et al. Am J Psychiatry 2001;158:213-219.
O’Hara MW. Arch Gen Psychiatry 1986;43:569-573.
Gotlib IH et al. J Consult Clin Psychol 1989;57:269-274. Evans J et al. BMJ 2001;323:257-260.
National Violent Death Reporting
System Map
Maternal Mortality: Violent Death vs. Specific Obstetric
Causes
*data from 2003–2007 NVDRS (pregnancy-associated homicide and suicide; this analysis)
and Berg et al. 201038 (pregnancy-related mortality due to hemorrhage; hypertensive
disorders; amniotic fluid embolism); deaths from specific obstetric causes are calculated
as deaths during pregnancy or within the first year postpartum. Palladino, et al. 2011.
Suicidal / Homicidal Ideation
• Pregnancy
– Thoughts of Death and Dying in Pregnant
Women with Mental Illness (Newport et al
2007)
16.9 – 33.1% positive depending on scale
utilized. Highest for self-report measures
Risk Factors
– Current Depression
– Co-morbid Anxiety Disorder
– Unplanned Pregnancy
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
Bipolar Disorder Relapse (n=89)
Viguera et al – AJP 2007
Postpartum Depression:
Clinical Predictors
MDD = Major depressive disorder.
O’Hara MW, et al. J Abnorm Psychol 1991;100:63-73.
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
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Antenatal Maternal Depression: Acute
Maternal & Neonatal Consequences
•
•
Non-compliance with
prenatal care
•
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
Low APGAR scores
– 14-15% use EtOH
– 3% use illicit drugs
•
•
Not bonding with baby
•
Neonatal Complications
•
Effects on family
•
Admission to NICU
•
Suicide
•
Fetal demise
•
Postpartum Depression
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)
Emerging View of Infant Development
(genetics)
(environment)
Impact of Glucocorticoids
Audience Response Question
Depression during Pregnancy
• Which of the following statements is false ?
– A. Greater than 5% of pregnant women receive a
Rx for an Antidepressant.
– B. Depression during pregnancy is typically mild
and does not impair function.
– C. Depression during pregnancy increases the
risk for Postpartum Depression.
– D. Depression increases the risk for pre-term
delivery.
– E. The majority of mental illnesses do not
improve during pregnancy.
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Treatment
Options
Medications
Psychotherapy
ECT
Light Therapy*
TCMS*
Exercise*
* Limited data
“Paper or plastic?”
”
Treatment Options
• No randomized controlled trials of treatment
options during pregnancy
• It is a laudable goal to avoid medication
exposures during pregnancy
– Other treatments may not be routinely
available
– Therapy $ > Medication Management $
“to be effective, a treatment must be
available and affordable”
Use of ECT during pregnancy.
•
•
Miller LJ. Hosp Community Psychiatry. 1994 May;45(5):444-50.
–
A total of 300 case reports of ECT during pregnancy drawn from the literature from 1942 through
1991 were reviewed.
–
Only 28 reported complications. Including transient, benign fetal arrhythmias; mild vaginal
bleeding; abdominal pain; and self-limited uterine contractions. Without proper preparation, there
was also increased likelihood of aspiration, aortocaval compression, and respiratory alkalosis.
–
CONCLUSIONS: Preparation for ECT during pregnancy should include a pelvic examination,
discontinuation of nonessential anticholinergic medication, uterine tocodynamometry, intravenous
hydration, and administration of a nonparticulate antacid. During ECT, elevation of the pregnant
woman's right hip, external fetal cardiac monitoring, intubation, and avoidance of excessive
hyperventilation
Leiknes KA, Cooke MJ, Jarosch-von Schweder L, Harboe I, Høie B. Arch Womens Ment
Health. 2013 Nov 24. [Epub ahead of print]
–
A systematic search was undertaken in the databases Medline, Embase, PsycINFO, SveMed
and CINAHL (EBSCO). Studies and extracted data were sorted according to before and after
year 1970, due to changes in ECT administration over time.
–
A total of 67 case reports 169 pregnant women were identified, treated during pregnancy with a
mean number of 9.4 ECTs,
–
Adverse events such as fetal heart rate reduction, uterine contractions, and premature labor (born
between 29 and 37 gestation weeks) were reported for nearly one third (29 %).
–
ECT during pregnancy is advised considered only as last resort treatment under very stringent
diagnostic and clinical indications. Updated international guidelines are urgently needed.
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
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 .
Metabolic Capacity
-P450 Enzymes
-Glucoronidation
Amniotic Fluid
P-glycoprotein
BCRP
Physicochemical
Metabolic Capacity
-protein binding
-P450 Enzymes
-lipophilic (octanol partition)
-Glucoronidation
-molecular weight
?
P-glycoprotein
BCRP
PLACENTAL PASSAGE OF MEDICATIONS (n=512)
Ratio [Umbilical Cord] / [ Maternal Serum]
250
200
150
100
50
Li
LT
G
VP
A
CB
Z
RI
S
Q
UI
O
LZ
H
AL
CL
O
N
BU
P
C
IT
FL
U
PA
R
SE
RT
0
(Newport et al AJP 2007; Stowe et al unpublished data)
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Prospective Studies
Antidepressants & Major Malformations
Registry / Antidepressant
(n)
% Major
Malformations
NY Dept of Health (95-01)1
1,816,343
4.09%
Swedish Registry (95-01)2
637,651
3.50%
Fluoxetine
4,679
2.69%
Sertraline
3,393
1.95%
Citalopram
2,688
2.72%
Paroxetine
2,687
3.50%
Bupropion
2,550
2.20%
Venlafaxine
771
1.82%
Escitalopram
235
3.40%
1http://www.health.state.ny.us/nysdoh/cmr/docs
2http://www.sos.sos.se/epc/epceng.htm
Additional Studies of Birth Defects
• Alwan et al, 2007 NEJM
– No overall congenital heart defects
– As a group, increased risk of Anencephaly (OR 2.4);
Craniosynostosis (OR 2.5); Omphalocele (OR 2.8)
• Louik et al, 2007 NEJM
– 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
– SSRIs overall increase risk of septal defects (OR 1.99)
– Multiple SSRIs, OR 4.70
AD and Risk for Major Malformations –
Summary
• There are a myriad of studies.
• Numerous methodological considerations.
– Controls do not take AD
• There is NO consistent pattern of AD
associated birth defects.
• Septal defects reports
– ? Clinical significance
– Role of prostaglandins
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%
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
(2009)
cohort study
third-trimester SSRIexposed and nonexposed
N=5; two SSRI- No association
exposed
25,214 infants; 2.3% SSRI- N=16; 0 SSRIexposed
exposed
Prospectively
collected exposure
data
Underpowered to detect small
effects
Wichman et
al. (2009)
Retrospective cohort
study
No association
Prospectively
Small SSRI-exposed sample;
collected information underpowered to detect small
effects
Wilson et al.
(2011)
11,923 infants; 1:6 ratio of
Case-control study;
PPHN identified via echo PPHN patients and healthy
or difference in pre- and infants; number of SSRIpostductal oxygen
exposed not reported
saturation
N=20; 0 SSRIexposed
No association
Explicit diagnostic
criteria for PPHN;
prospectively
captured prescription
information
Chambers et
al. (2006)
Multicenter case-control 1,213 infants; 1:2 ratio of
study
PPHN patients and healthy
infants; 3% SSRI-exposed
N=377; 16
SSRI-exposed
Odds ratio=6.1 (95%
CI=2.2–16.8)
Large number of
Exposures based on telephone
PPHN cases; required interviews with only 70%
exposure after 20
participation (potential recall
weeks
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
Källén and
Olausson
(2008)
Population-based
831,324 infants; 0.9%
retrospective cohort
SSRI-exposed
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 See Källén and
risk=2.4 (95% CI=1.29–
Olausson (2008)
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)
Incidence of SSRI use in
population unreported; no
control for length of gestation
beyond exclusion of <34
weeks
Positive
findings
Reis and
Extended version of
Källén (2010) Källén and Olausson
study (2008)
1,251,070 infants; 1.2%
SSRI-exposed
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
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 ?
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.
AD in Pregnancy – Patient Education –
Summary
• One area 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.
Can we isolate the impact of illness
from the impact of treatment ?
SSRIs & Neonatal Adaptation
Population Study: British Columbia Linked Health Database
Outcomes
(Means / %)
Outcome
CTL
MDD
No Rx
Outcome
Differences
MDD
Rx
CTL vs.
MDD No Rx
MDD No Rx
vs. MDD Rx
MATCHED
MDD No Rx
vs. MDD Rx
C-Section (%)
19.0
21.0
24.0
1.0, p<.01
3.0, p<.01
-0.9, p<.69
Birth Weight (g)
3453
3429
3397
-24, p<.001
-32, p<.05
10, p<.72
EGA Delivery (wks)
39.2
39.1
38.8
-0.06, p<.001
-0.35, p<.001
-0.14, p<.18
Preterm Birth (%)
5.9
6.5
9.0
0.6, p<.007
2.5, p<.001
0.7, p<.61
SGA (%)
7.4
8.1
8.5
0.7, p<.005
0.5, p<.51
3.3, p<.02
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
Hospital Stay (days)
Convulsions (%)
(n=119,547)
46
MDD
SSRI
Oberlander TF et al. Arch Gen Psychiatry 2006; 63: 898-906
Why such overlap between
depression and antidepressants ?
• Psychiatric Illness Diathesis – associated with
higher rate non-optimal outcomes
• Co-morbid Medical Illnesses
– Higher BMI, diabetes, hypertension
• Behavioral Patterns
– Exposures: over the counter, smoking, etc.
• Early Life Events
• Other
Audience Response Question
Depression during Pregnancy
• Which of the following statements is false ?
– A. The overall rate of birth defects is increased
with antidepressant exposure.
– B. Antidepressant exposure in pregnancy is
associated with a higher rate of respiratory
problems in neonates.
– C. Antidepressant neonatal abstinence syndrome
is a serious condition requiring treatment.
– D. All antidepressants cross the human placental
barrier.
– E. Non-pharmacological interventions are
effective treatment options for depression during
pregnancy.
Depression in Pregnancy –
What do we know ?
• Course / Severity of Illness
• Impact of Illness
• Treatment Options
• Impact of Treatment
• Approaching Common Clinical Situations
Depression 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
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’
Screen for DEPRESSION
Negative
Positive
EPDS, PHQ9, Interview
Yes
Risk Factors for Depression
Document risk factors and
continue to monitor for
depression
No
Medical Work Up – CBC,
CMP, TSH, RPR, UDS
+ Urine Drug Screen
(Refer to appropriate treatment
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
and re-test in pregnancy)
Development treatment
plan for postpartum period
+Nicotine Use
(Encourage abstinence , provide
resources, and document on
follow up)
Yes
1.
2.
3.
4.
Yes
History of previous
treatment for depression?
Prior Treatment
Effective ?
No
Is patient willing to Accept
treatment for depression ?
Yes
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
Electroconvulsive
Therapy (ECT)
-Safe in pregnancy
-Use in severe
cases or Rx failures
-Limited
availability
No
Document education about
depression, and continue to
monitor
“Effective Treatment = Relative Safety + Available + Affordable”
Evaluate reproductive
safety information of
prior treatment.
Prior pregnancy
exposure.
Risk/ Benefit
Assessment for prior
treatment.
Initiation of prior
treatment if indicated
and available.
Treat as
Indicated, and reevaluate for
depression
Pharmacological
-SSRIs, SNRIs, TCAs
Development treatment
plan for postpartum period
Non-Pharmacological
-relaxation, stress reduction, meditation
-Supportive psychotherapy
-Interpersonal psychotherapy (IPT)
-Cognitive Behavioral Therapy (CBT)
-Couples Therapy
-Bright Light Therapy
-Transcranial Magnetic Stimulation
(TMS)
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
Dosing Strategies
Comments
Lactation
Citalopram
(Celexa)
+++
++
Start on 5-10 mg x 2-4 days, then
increase.
Range 10-40 mg/day
20 mg tablet on $4
list
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
20 mg capsule on
$4 list
Sertraline
(Zoloft)
+++
++++
Start 25 mg x 2-4 days, then
increase.
Range 25-200 mg/day
50 mg tablet on
most $4 lists
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.
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
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 for healthy
infant/child development.
So I Hope this Clears Things Up