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Understanding Postpartum Understanding Postpartum Depression: The Role of the Depression: The Role of the
Pediatric ProviderPediatric Provider
Samantha Meltzer-Brody, M.D., M.P.H.Samantha Meltzer-Brody, M.D., M.P.H.
Director, Perinatal Psychiatry ProgramDirector, Perinatal Psychiatry Program
UNC Center for Women’s Mood DisordersUNC Center for Women’s Mood Disorders
Funding SupportFunding Support
NIH K23MH085165 Mentored Career Development Award
AstraZeneca Foundation of Hope
Overview of TalkOverview of Talk
Epidemiology of MDD & PPDEpidemiology of MDD & PPD
Barriers to Screening Faced by Barriers to Screening Faced by PediatriciansPediatricians
How to ScreenHow to Screen
Pre-term Infants and Maternal Risk of PPDPre-term Infants and Maternal Risk of PPD
Current Theories of the Pathogenesis of Current Theories of the Pathogenesis of PPDPPD
Treatment of Perinatal DepressionTreatment of Perinatal Depression
Perinatal Perinatal depression depression is very real is very real and and treatable.treatable.
Mood Disorders in Women Mood Disorders in Women in the General Populationin the General Population
Depressive disorders are very commonDepressive disorders are very common
Lifetime prevalence rates range from 4.9-17.1 Lifetime prevalence rates range from 4.9-17.1 percentpercent
Women report a history of major depression at Women report a history of major depression at nearly twice the rate of mennearly twice the rate of men
Depression is now considered the leading Depression is now considered the leading cause of disease-related disability among cause of disease-related disability among women in the world.women in the world.
Women of childbearing age are at high risk Women of childbearing age are at high risk for major depressionfor major depression
DSM-IV Criteria for Major DSM-IV Criteria for Major DepressionDepression
Five (or more) of 9 symptoms:Five (or more) of 9 symptoms: Depressed moodDepressed mood Loss of interest or pleasure in almost all Loss of interest or pleasure in almost all
activitiesactivities Significant weight loss or weight gainSignificant weight loss or weight gain Insomnia or hypersomniaInsomnia or hypersomnia Restlessness or feeling slowed downRestlessness or feeling slowed down FatigueFatigue Worthlessness or inappropriate guiltWorthlessness or inappropriate guilt Inability to concentrateInability to concentrate Suicidal ideationSuicidal ideation
DSM-IV Criteria for Major DSM-IV Criteria for Major Depression (MDD)Depression (MDD)
Must be present during the same 2-week Must be present during the same 2-week period period
Represents a change from previous Represents a change from previous functioningfunctioning At least one of the symptoms is either At least one of the symptoms is either
(1) depressed mood or (1) depressed mood or (2) loss of interest or pleasure(2) loss of interest or pleasure
Background: Perinatal Depression
COMMON 10-15% prevalence 4 million women give birth annually in U.S.; ½ million
with PPD Most common, unrecognized complication of perinatal
period Compare to prevalence rate of gestational diabetes at
2-5%
MORBID Devastating consequences for patient and family
low maternal weight gain, preterm birth Impaired bonding between mother and infant Increased risk of suicide and infanticide
MISSED No practice guidelines or routine screening Symptoms often different from “classic DSM-IV
depression”Gavin et al, Ob & Gyn 2005; Gaynes et al. AHRQ
Systematic Review 2005
Perinatal Mood Disorders: Perinatal Mood Disorders: EtiologyEtiology
Caused primarily by hormonal changesCaused primarily by hormonal changes
Life stressors, such as moving, illness, Life stressors, such as moving, illness, poor partner support, financial problems, poor partner support, financial problems, and social isolation can negatively affect and social isolation can negatively affect the woman’s mental statethe woman’s mental state
Strong emotional, social, and physical Strong emotional, social, and physical
support can greatly facilitate her recoverysupport can greatly facilitate her recovery
Distinguishing Characteristics
of Mood Symptoms in the
Perinatal Period• Anxiety or agitation
• Depressed mood• Sadness, weepiness • Irritability• Lack of interest in the
newborn• Impaired
concentration or feeling overwhelmed
• Feelings of dependency
Causes of Perinatal Mood Causes of Perinatal Mood SymptomsSymptoms
"Giving birth is like taking your lower lip and forcing it "Giving birth is like taking your lower lip and forcing it over your head.“ --Carol Burnettover your head.“ --Carol Burnett
• • Rapid hormonal changes Rapid hormonal changes • • Physical and emotional stress of birthingPhysical and emotional stress of birthing• • Physical discomforts Physical discomforts • • Emotional letdown after pregnancy and/or birth Emotional letdown after pregnancy and/or birth • • Awareness and anxiety about increased Awareness and anxiety about increased
responsibility responsibility • • Fatigue and sleep deprivationFatigue and sleep deprivation• • Disappointments including the birth, spousal Disappointments including the birth, spousal
support, nursing, and the babysupport, nursing, and the baby
Perinatal Psychiatric Perinatal Psychiatric DisordersDisorders
Depression During Depression During PregnancyPregnancy
Postpartum Blues Postpartum Blues (Not considered a disorder)(Not considered a disorder)
Postpartum DepressionPostpartum Depression Postpartum PsychosisPostpartum Psychosis Bipolar DisorderBipolar Disorder Anxiety DisordersAnxiety Disorders
(OCD, Panic Disorder, (OCD, Panic Disorder, PTSD)PTSD)
Risks factors associated Risks factors associated with PPDwith PPD
• • Depression or anxiety during pregnancy Depression or anxiety during pregnancy • Personal or family history of • Personal or family history of depression/anxiety depression/anxiety • Abrupt weaning • Abrupt weaning • Social isolation or poor support • Social isolation or poor support • Child-care related stressors • Child-care related stressors • • Stressful life eventsStressful life events• • Mood changes while taking birth control Mood changes while taking birth control pill or pill or fertility medication, such as fertility medication, such as Clomid Clomid • Thyroid dysfunction • Thyroid dysfunction • • 50 to 80%50 to 80% risk if previous episode of PPD risk if previous episode of PPD
Postpartum PsychosisPostpartum Psychosis
Postpartum PsychosisPostpartum Psychosis A rare condition, with an estimated prevalence A rare condition, with an estimated prevalence
of 0.1%-0.2% (one to two per thousand)of 0.1%-0.2% (one to two per thousand) However, in women with Bipolar Disorder, However, in women with Bipolar Disorder,
the risk is 100 times higher at 10% - 20%the risk is 100 times higher at 10% - 20% It is a It is a psychiatric emergencypsychiatric emergency & requires & requires
immediate treatment with a mood stabilizer immediate treatment with a mood stabilizer & antipsychotic& antipsychotic
Onset usually 2-3 days postpartumOnset usually 2-3 days postpartum Has a 5 % suicide & 4 % infanticide rate Has a 5 % suicide & 4 % infanticide rate Risk for recurrent episode with a subsequent Risk for recurrent episode with a subsequent
pregnancy is 90%pregnancy is 90%
Screening for PPD By Screening for PPD By PediatriciansPediatricians
Pediatricians have greater awareness of Pediatricians have greater awareness of the negative consequences for mother the negative consequences for mother and child.and child.
Most studies demonstrate that Most studies demonstrate that pediatricians do not feel responsible for pediatricians do not feel responsible for recognizing postpartum depression. recognizing postpartum depression.
Unfamiliar with screening tools for PPD.Unfamiliar with screening tools for PPD. Heneghan et al, 2000; Olson et al, 2002; Currie et al, Heneghan et al, 2000; Olson et al, 2002; Currie et al,
2004; 2004; Wiley et al, 2004Wiley et al, 2004
Frequency of HealthCare Frequency of HealthCare Provider Contact in 1Provider Contact in 1stst year year
PostpartumPostpartum 1 visit to Ob-Gyn at 6-week postpartum 1 visit to Ob-Gyn at 6-week postpartum
visitvisit 5-7 visits to Pediatrician in the first year 5-7 visits to Pediatrician in the first year
after giving birthafter giving birth Maternal encounters with Pediatrician are Maternal encounters with Pediatrician are
> than with OB-GYN> than with OB-GYN Pediatricians play a critical role in:Pediatricians play a critical role in:
DetectionDetection EvaluationEvaluation Referral Referral Follow-up of PPD Follow-up of PPD
Barriers to Diagnosis & Treatment
Pregnant Pause May 2009
Vogue Article Slams Antidepressants During Pregnancy
Postpartum Depression: Do All Moms Need Screening? July 20, 2009
Pediatrician Barriers to Pediatrician Barriers to Screening For PPDScreening For PPD
Insufficient time for adequate history takingInsufficient time for adequate history taking Insufficient training or knowledge to diagnose, Insufficient training or knowledge to diagnose,
counsel or treatcounsel or treat Maternal reluctance to discuss with PediatricianMaternal reluctance to discuss with Pediatrician Pediatrician reluctance to discuss mental health Pediatrician reluctance to discuss mental health
issueissue Lack of mental health resources for referralLack of mental health resources for referral
Current Screening Current Screening Strategies for PPDStrategies for PPD
The The best carebest care we currently have to offer is to we currently have to offer is to provide routine screening of all postpartum provide routine screening of all postpartum women (i.e., diagnose PPD after it has women (i.e., diagnose PPD after it has already started). already started).
Although well-validated screening Although well-validated screening instruments developed specifically for use instruments developed specifically for use during the perinatal period are readily during the perinatal period are readily available (e.g., Edinburgh Postnatal available (e.g., Edinburgh Postnatal Depression Scale, EPDS) or PPD Screening Depression Scale, EPDS) or PPD Screening Scale, PDSS), these instruments are Scale, PDSS), these instruments are unableunable to prospectively identify who is at risk for the to prospectively identify who is at risk for the development of PPD. development of PPD.
Screening InstrumentsScreening Instruments
Edinburgh Postnatal Depression Scale Edinburgh Postnatal Depression Scale (EPDS)(EPDS)
Most commonly employed screening tool Most commonly employed screening tool for PPDfor PPD
10 questions self-rated instrument10 questions self-rated instrument Validated and developed specifically to Validated and developed specifically to
identify women experiencing postnatal identify women experiencing postnatal depression depression
English and Spanish versionsEnglish and Spanish versions
Edinburgh Postnatal Depression Scale (EPDS)1,2
Ask patient how they have been feeling OVER THE LAST 7 DAYS, not just today
To use calculator, click on appropriate answer and score appears in box when all questions completed
1. I have been able to laugh and see the funny side of things
2. I have looked forward with enjoyment to things
3. I have blamed myself unnecessarily when things went wrong
4. I have been anxious or worried for no good reason
5. I have felt scared or panicky for no very good reason
6. Things have been getting on top of me
7. I have been so unhappy, I have had difficulty sleeping
8. I have felt sad and miserable
9. I have been so unhappy that I have been crying
10. The thought of harming myself has occurred to me
Edinburgh Postnatal Depression Score = /30
3 points - Yes, quite often2 point - Sometimes1 point - Hardly ever0 points - Never
Implementing EPDS in Implementing EPDS in Pediatric SettingsPediatric Settings
Universal screening implemented for PPD Universal screening implemented for PPD during well-child visits in the 1during well-child visits in the 1stst year. year.
27% of women had a positive screen at 27% of women had a positive screen at some point in that yearsome point in that year
Increased documentation of maternal Increased documentation of maternal depressiondepression
Increased rates of mental health referralIncreased rates of mental health referral SCREENING IS FEASIBLESCREENING IS FEASIBLE
Chaudron et al, 2004Chaudron et al, 2004
Factors Associated with Factors Associated with Screening in Pediatric Screening in Pediatric
Settings Settings Age (older pediatricians)Age (older pediatricians) Practices provide child mental health Practices provide child mental health
servicesservices Race of patient population (>75% white)Race of patient population (>75% white) Use multiple methods for identification of Use multiple methods for identification of
maternal depressionmaternal depression Observation is inadequate!!Observation is inadequate!!
Believe that PPD is adverse effect on childBelieve that PPD is adverse effect on child Inclined to treat depression (96% refer)Inclined to treat depression (96% refer)
Heneghan et al, 2007Heneghan et al, 2007
Pathogenesis of Unique Symptoms in PPD is Unknown
Research questionnaire given to patients presenting to the UNC Women’s Mood Disorders Program
Survey focused on psychiatric comorbidity and prior stress related-events in women with perinatal depression
Planned preliminary analysis of patients presenting with PPD
Used validated measures for psychiatric illness State/Trait Anxiety Inventory Patient Health Questionnaire Edinburgh Postnatal Depression Scale SPAN Post Traumatic Stress Disorder Scale Trauma Inventory
Recruitment of Study Sample
Total NumberApproached in WMD Clinic
N=281
Consented but Incomplete N=37
Refused N=21
Completed WMD SurveysN=231
N=158
N=101 postpartum N=57 pregnant
Results: DemographicsSample Size N=158
Mean Age (years) 30
Mean Education (years)
15.2
Edinburgh Postnatal Depression Score
14 (>12 is positive)
PHQ Depression Score
10.3 (>10 is positive for moderate to severe)
Results: Comorbid
Psychiatric Diagnoses in Study Population
0
10
20
30
40
50
60
StudyPop
Panic
Abuse
PTSD
Rates of Comorbid
Psychiatric Diagnoses
0
10
20
30
40
50
60
StudyPop
GenPop
Panic
Abuse
PTSD
State and Trait Anxiety Correlated with Worse
Comorbidity EPDS PHQ Dep Panic
D/OPositive Screen for PTSD
State Anxiety
R=.70P<.0001
R=.51P<.0001
R=.25P<.002
R=.66P<.0001
Trait Anxiety
R=.74P<.0001
R=.48P<.0001
R=.31P=.0001
R=.57P<.0001State anxiety = current level of anxiety (79th percentile compared to pop)
Trait anxiety = usual degree of anxiety (92nd percentile compared to pop)
UNC OB-GYN PPD Algorithm
Posted on the Mombaby.org website Look Under Algorithms
Edinburgh (English) Edinburgh (Spanish) Edinburgh Triage Algorithm
See handout of algorithm
Preterm Infants and Preterm Infants and Maternal Risk of PPDMaternal Risk of PPD
Higher rates of anxiety and depression Higher rates of anxiety and depression (prevalence rate of depression of at least (prevalence rate of depression of at least 50%), during the first 6 months postpartum 50%), during the first 6 months postpartum
Risk factors in this population:Risk factors in this population: mother’s past psychiatric historymother’s past psychiatric history previous perinatal lossprevious perinatal loss psychosocial support including marital statuspsychosocial support including marital status severity of the infant’s health statusseverity of the infant’s health status degree of worry and coping skills in the motherdegree of worry and coping skills in the mother rehospitalization after the initial stayrehospitalization after the initial stay
(Miles et al, 2007; Garel et al, 2004; Mew et al, (Miles et al, 2007; Garel et al, 2004; Mew et al, 2003)2003)
Increased Psychiatric Comorbidity Increased Psychiatric Comorbidity After Preterm BirthAfter Preterm Birth
Correlation between PTSD symptoms and Correlation between PTSD symptoms and preterm delivery preterm delivery
Increased PTSD symptoms in women who have Increased PTSD symptoms in women who have had a “traumatic” birth experience. had a “traumatic” birth experience.
PTSD and depression are often comorbidPTSD and depression are often comorbid Integrated care is needed between obstetricals Integrated care is needed between obstetricals
mental health, and neonatology/pediatrics mental health, and neonatology/pediatrics ““Will allow for the development of innovative Will allow for the development of innovative
assessment and treatment strategies to help assessment and treatment strategies to help the mother-infant dyad throughout the difficult the mother-infant dyad throughout the difficult first year and beyond after a preterm delivery”. first year and beyond after a preterm delivery”.
(Holditch-Davis et al, 2003; Rogal et al, 2007),(Holditch-Davis et al, 2003; Rogal et al, 2007),
Etiology of PPDEtiology of PPD
Change in level of gonadal steroidsChange in level of gonadal steroids Interaction of gonadal steroids with Interaction of gonadal steroids with
other neurotransmitter systemsother neurotransmitter systems Dysregulation of HPA axisDysregulation of HPA axis Genetic vulnerabilityGenetic vulnerability
Neurobiologic Effects of Neurobiologic Effects of Estrogen and Estrogen and ProgesteroneProgesterone
Both estrogen and, progesterone Both estrogen and, progesterone affect neurons in the opioid, affect neurons in the opioid, norepinephrine, serotonin, norepinephrine, serotonin, dopamine and GABA systemsdopamine and GABA systems
Receptors for estrogen and Receptors for estrogen and progesterone have been identified progesterone have been identified in multiple areas of the CNS in multiple areas of the CNS including amygdala, hippocampus, including amygdala, hippocampus, cingulate gyrus, locus coeruleus cingulate gyrus, locus coeruleus and central gray matterand central gray matter
Pathogenesis of PPD:Working Hypotheses
Abnormalities in HPA axis activity are associated with reproductive-endocrine related mood disorders, particularly during the transition from childbirth to the immediate postpartum period
HPA AxisHPA Axis
Abnormal HPA changes in Abnormal HPA changes in women with Depressionwomen with Depression
Dysregulation of the HPA axis may represent a Dysregulation of the HPA axis may represent a critical maladaptation and vulnerability to the critical maladaptation and vulnerability to the onset of reproductive steroid related depressiononset of reproductive steroid related depression
A hallmark feature of the HPA axis in MDD is A hallmark feature of the HPA axis in MDD is altered response to stress and inability to altered response to stress and inability to maintain regulationmaintain regulation
Hyperactivity of the HPA axis is one of the most Hyperactivity of the HPA axis is one of the most robust biological findings in MDD robust biological findings in MDD
Activity of the HPA axis is often evaluated by Activity of the HPA axis is often evaluated by the dexamethasone suppression test (DST) the dexamethasone suppression test (DST)
a positive (abnormal) DST is characterized by a positive (abnormal) DST is characterized by diminished or absent suppression of cortisol, resulting diminished or absent suppression of cortisol, resulting in hyperactivity of the HPA axis in hyperactivity of the HPA axis
Normal changes in the HPA axis during pregnancy and into the postpartum period
The third trimester of pregnancy is characterized by high estrogen and progesterone levels and a hyperactive HPA axis with high plasma cortisol
At childbirth and during the transition to the postpartum period the following occur:
estrogen and progesterone rapidly decline there is blunted HPA axis activity due to
suppressed hypothalamic CRH secretion
Mean plasma concentrations of estrone (E1), estradiol (E2), estriol (E3), and progesterone (P) during pregnancy. (Data from Tulchinsky D, et al 1972; Levitz M et al 1977;35:109.)
Sequential Measurements of Plasma CRH, ACTH, Cortisol, & Urinary Free Cortisol During Pregnancy
WEEKS OF GESTATION
CRH (PG/ML)
ACTH (PG/ML)
CORTISOL (MG/DL)
DHEAS (MG/DL)
ALDOSTERONE (PG/ML)
URINARY FREE CORTISOL (MG/24 H)
11–15 115 ± 45 8.8 ± 2.8 10.5 ± 1.4 102 ± 14 412 ± 63.6 54.8 ± 7.3
21–25 145 ± 30 9.8 ± 1.5 20.0 ± 1.1[] 85.1 ± 9.0 487 ± 42.8 84.4 ± 8.4
31–35 1,570 ± 349[]
12.1 ± 2.0 22.0 ± 1.2[] 62.6 ± 6.8[] 766 ± 94 105 ± 8.8[*]
36–40 4,346 ± 754[*]
18.6 ± 2.6[*]
26.0 ± 1.1[*] 63.8 ± 7.1[*] 1,150 ± 170[*] 111 ± 8.7[*]
HPA Axis and Impact on FetusNormal Development
Increased fetal cortisol contributes to the maturation of organ systems required for postnatal extra-uterine survival (Challis et al, 2001).
Fetal endocrine maturation is characterized by enhanced activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis during late gestation.
Precocious activation of this axis may occur when the fetus is exposed to an adverse intra-uterine environment such as: Hypoxemia. Disruption of early embryonic environment This environment may have a significant role to play in
determining the timing and level of the prepartum activation of the HPA axis and on the functional capacity of the axis to respond to stress in later life (McMillen et al, 2004).
HPA Axis and Impact on HPA Axis and Impact on FetusFetus
Abnormal StressAbnormal Stress Prenatal stress and exogenous glucocorticoid Prenatal stress and exogenous glucocorticoid
manipulation also lead to the modification of manipulation also lead to the modification of behaviour, brain and organ morphology, as well behaviour, brain and organ morphology, as well as altered regulation of other endocrine as altered regulation of other endocrine systems systems
Excessive levels of feto-placental Excessive levels of feto-placental glucocorticoid, derived from maternal glucocorticoid, derived from maternal administration of synthetic corticosteroids or administration of synthetic corticosteroids or sustained endogenous fetal cortisol production, sustained endogenous fetal cortisol production, results in intrauterine growth restrictionresults in intrauterine growth restriction
Primary area of research at the Emory Primary area of research at the Emory Women’s Mental Health Program (Drs. Stowe Women’s Mental Health Program (Drs. Stowe and Newport)and Newport)
Rapid Decrease in Hormones in the
Postpartum Period
TreatmentTreatment
Treatment of PPDTreatment of PPD
Critical for the well being of the woman, Critical for the well being of the woman, baby and familybaby and family
Effective treatments are readily availableEffective treatments are readily available
Skilled assessment and treatment by Skilled assessment and treatment by mental health professionals in perinatal mental health professionals in perinatal psychiatry makes a difference in psychiatry makes a difference in outcomes !!outcomes !!
Issues Related to Issues Related to Treatment of Perinatal Treatment of Perinatal
DepressionDepression Treatment must include both Treatment must include both
psychological and/or biological psychological and/or biological interventionsinterventions
Psychotherapy (individual and/or group)Psychotherapy (individual and/or group) Increased social supportsIncreased social supports Exercise, good nutrition, adequate sleepExercise, good nutrition, adequate sleep Antidepressant medications if appropriateAntidepressant medications if appropriate Careful monitoringCareful monitoring
ToonToon
Risk of Relapse of Major Risk of Relapse of Major Depression in PregnancyDepression in Pregnancy
High risk of depressive relapse following High risk of depressive relapse following antidepressant discontinuation during antidepressant discontinuation during pregnancy ( Cohen et al, JAMA, 2006).pregnancy ( Cohen et al, JAMA, 2006). Of 201 women in the sample, 86 (43%) experienced Of 201 women in the sample, 86 (43%) experienced
a relapse of major depression during pregnancy.a relapse of major depression during pregnancy. Women who discontinued medication relapsed Women who discontinued medication relapsed
significantly more frequently (68% vs 26%) significantly more frequently (68% vs 26%) compared with women who maintained their compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001). interval, 2.8-9.1; P<.001).
Pregnancy is not "protective" with respect to risk Pregnancy is not "protective" with respect to risk of relapse of major depressionof relapse of major depression
Risks of Untreated Antenatal Depresion
Associated with low maternal weight gain, increased rates of preterm birth, low birth weight, increased rates of cigarette, alcohol and other substance use,
Increased ambivalence about the pregnancy and overall worse health status.
Prenatal exposure to maternal stress has been shown to have consequences for the development of infant temperament.
Children exposed to perinatal maternal depression have higher cortisol levels than infants of mothers who were not depressed, and this continues through adolescence.
Maternal treatment of depression during pregnancy appears to help normalize infant cortisol levels.
Why is the Use of Antidepressants During
Pregnancy Controversial ? Antidepressants are often
considered “luxury” medications. Antidepressants are often prescribed
in patients that do not meet full diagnostic criteria for MDD or other psychiatric illness.
Discontinuation of antidepressants during pregnancy has risks.
Pharmacotherapy in Pregnancy
All psychotropics cross the placenta and none are approved by the FDA for use during pregnancy.
Unethical to conduct randomized placebo controlled studies on medication safety in pregnant women.
Thus, most information about the reproductive safety of of drugs comes from case reports and retrospective studies.
Prevalence of SSRI’s in pregnancy is 6%-8%
Antidepressants Tx in Pregnancy: Neonatal Outcomes
SSRI withdrawal is possible but usually these are transient (restlessness, rigidity, tremor)
Late SSRI exposure carries an overall risk ratio of 3.0 (95% CI, 2.0-4.4) for a neonatal behavioral syndrome -Moses-Kolko et al, JAMA, 2005
Neonatal behavioral syndrome in 31.5% of infants in late-exposed group, 8.9% in early-exposure group for fluoxetine (Chambers et al, NEJM, 1996)
Paroxetine and Pregnancy
In 2005, FDA began investigated risks associated with antidepressant use in pregnant women
Results of Investigation: Infants born to women taking Paroxetine
(Paxil) may be at double the risk for cardiovascular birth defects (4%) compared to other antidepressants (2%)
Sept. 2005, U.S health officials warned against the use of Paxil in the first trimester due to potential birth defects in infants, though relationship may be incidental
Further research is necessary, involving adequate, well-controlled studies to prove the effects of Paxil on the fetus
Primary Pulmonary Hypertension
of the Newborn 2006, case control study showed SSRI
exposure after 20 weeks gestation increased risk (4-5x higher) of PPHN with absolute risk of <1%. (N. England J. Med, 2006)
Recent studies show increased risk of PPHN with multiple other risk factors and absolute low risk with SSRI exposure C-section, high maternal BMI, AA or Asian
heritage Study concluded that large BMI and C-section
had greater risk than SSRI exposure. (Pediatrics, 2007)
Swedish Medical Birth Register– 3rd trimester exposure showed increased risk of 2.4 (Pharmacoepidemiology Drug Safety, 2008)
What to do?What to do? SSRIs (especially fluoxetine and sertraline) and SSRIs (especially fluoxetine and sertraline) and
TCAs relatively safe even during first trimester.TCAs relatively safe even during first trimester. SSRIs (especially sertraline) and TCAs relatively safe SSRIs (especially sertraline) and TCAs relatively safe
in breast-feeding. (Risk of fluoxetine accumulation in in breast-feeding. (Risk of fluoxetine accumulation in breastmilk and TCA-induced seizures. breastmilk and TCA-induced seizures.
Avoid Paroxetine (unless risk/benefit analysis Avoid Paroxetine (unless risk/benefit analysis dictates otherwise)dictates otherwise)
Insufficient information about newer antidepressants Insufficient information about newer antidepressants (SNRI’s), and trazodone.(SNRI’s), and trazodone.
Bupropion: FDA risk category B.Bupropion: FDA risk category B.
Psychotropic Use During Lactation
Risk-Benefit Assessment for Lactation
The majority of women plan to breastfeed
5%-17% of nursing women take medications
Breastfeeding is beneficial for the infant
All psychotropic medications studied to date are secreted in breast milk
Untreated maternal mental illness has an adverse effect on mother-infant attachment and infant development
Medication Starting dosage
Maximum dosage during lactation
Potential adverse event(s)
Selective serotonin reuptake inhibitors and other antidepressants
SERTRALINE 25mg 150-200mg Minimal detection of drug in infants serum (Weissman et al, 2004, Eberhard-Gran et al, 2006).
PAROXETINE 10mg 50mg Minimal detection of drug in infants serum (same references as for sertraline)
CITALOPRAM 10mg 60mg high milk/plasma concentration at higher doses (Eberhard-Gran et al, 2006).
FLUOXETINE 10mg 60mg Long half-life can increase the potential for accumulation (Eberhard-Gran et al, 2006)
ESCITALOPRAM 10mg 20mg Very limited data to date shows lower milk/plasma concentrations as compared to citalopram (Rampano et al, 2006)
MIRTAZEPINE 7.5mg 45mg Limited data available. Well tolerated in small study. Must always monitor for changes in sleep (sedation and activation), and changes in eating behaviors. (Kristensen et al, 2007).
BUPROPRION 75-150mg
300mg Limited data available. Small increased risk of infant seizure (case report). (Chaudron et al, 2004).
VENLAFAXINE N/A Inadequate data available
DULOXETINE N/A Inadequate data available
Clinical Pearls of Pharmacologic
Treatment All medication changes should be done prior to pregnancy if possible.
Ideally the patient should be stable psychiatrically for at least 3 months before attempting pregnancy.
Use medications that we know something about:
Older is usually better.. Minimize the number of exposures for the
baby. Consider breastfeeding when planning for
pregnancy. If a baby was exposed to a medication
during pregnancy, it may not make sense to discontinue the medication (or alternatively not breastfeed) for breastfeeding.
Conclusions: Treatment Perinatal psychiatric illness requires
immediate intervention. Coordination of care between OB-GYN and
trained mental health professionals is critical.
Antidepressant medications can be safely used during pregnancy and lactation Assess risk of untreated illness versus greater
risk of exposure. Chronic mental illness must be treated
during pregnancy to prevent severe PPD. Patients with preexisting psychosis must be
treated as a “high risk pregnancy” during and after delivery.
Collaborators at UNC David Rubinow, MD
Chairman of Psychiatry and Director of WMD Program
Amanda Dorn, MD & Edith Gettes, MD UNC Perinatal Psychiatrists at Rex Hospital
Location Cort Pedersen, MD
Professor of Psychiatry Christena Raines, NP
Perinatal Psychiatric Nurse Practitioner Elizabeth Bullard, MD
Medical Director, Inpatient Psychiatry Program
UNC Center for Women’s UNC Center for Women’s Mood Disorders:Mood Disorders:
Perinatal Psychiatry Perinatal Psychiatry ProgramProgram
Clinical and Research ProgramClinical and Research Program
that provides assessment, treatment that provides assessment, treatment
and support for women in the and support for women in the
perinatal periodperinatal period
Collaboration of doctors, nurses, Collaboration of doctors, nurses,
midwives, therapists, & social midwives, therapists, & social
workersworkers
www.womensmooddisorders.orgwww.womensmooddisorders.org
UNC Center for Women’s Mood Disorders:
Perinatal Psychiatry Inpatient Unit
Newest addition to the UNC Perinatal Psychiatry Program
1st Perinatal Inpatient Unit in the US Provides specialized comprehensive
assessment and treatment medication stabilization individual and group counseling and
behavioral therapy art therapy, relaxation, spirituality,
biofeedback, exercise, psycho-education for both patients and spouses
family therapy
Comfort Measures Protected sleep times Dedicated semi-private rooms and
group room Gliders and supplies for
pumping/nursing Pumps, supplies, and refrigerator for
milk storage Specialty perinatal nursing staff Extended visiting hours to
maximize positive mother-baby interaction
Patient ResourcesPatient Resources
Postpartum Support InternationalPostpartum Support Internationalwww.postpartum.netwww.postpartum.net
““Down Came the Rain” by Brooke ShieldsDown Came the Rain” by Brooke Shields
““This Isn’t What I Expected: Overcoming Postpartum This Isn’t What I Expected: Overcoming Postpartum Depression by Karen Kleiman & Valerie RaskinDepression by Karen Kleiman & Valerie Raskin
““Beyond the Blues” by Bennett & IndmanBeyond the Blues” by Bennett & Indman