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Understanding Postpartum Understanding Postpartum Depression: The Role of the Depression: The Role of the Pediatric Provider Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Director, Perinatal Psychiatry Program Program UNC Center for Women’s Mood Disorders UNC Center for Women’s Mood Disorders
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Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Dec 23, 2015

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Page 1: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 2: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Funding SupportFunding Support

NIH K23MH085165 Mentored Career Development Award

AstraZeneca Foundation of Hope

Page 3: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 4: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Perinatal Perinatal depression depression is very real is very real and and treatable.treatable.

Page 5: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 6: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 7: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 8: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 9: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 10: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 11: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 12: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 13: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 14: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Postpartum PsychosisPostpartum Psychosis

Page 15: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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%

Page 16: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 17: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 18: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Barriers to Diagnosis & Treatment

Pregnant Pause May 2009

Vogue Article Slams Antidepressants During Pregnancy

 

Page 19: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Postpartum Depression: Do All Moms Need Screening? July 20, 2009

Page 20: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 21: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 22: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 23: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 24: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 25: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 26: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 27: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 28: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 29: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Results: Comorbid

Psychiatric Diagnoses in Study Population

0

10

20

30

40

50

60

StudyPop

Panic

Abuse

PTSD

Page 30: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Rates of Comorbid

Psychiatric Diagnoses

0

10

20

30

40

50

60

StudyPop

GenPop

Panic

Abuse

PTSD

Page 31: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 32: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 33: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.
Page 34: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 35: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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),

Page 36: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 37: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 38: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 39: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

HPA AxisHPA Axis

Page 40: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 41: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 42: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.)

Page 43: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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[*]

Page 44: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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).

Page 45: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 46: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Rapid Decrease in Hormones in the

Postpartum Period

Page 47: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

TreatmentTreatment

Page 48: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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 !!

Page 49: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 50: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

ToonToon

Page 51: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 52: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 53: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 54: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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%

Page 55: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 56: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 57: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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)

Page 58: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 59: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

Psychotropic Use During Lactation

Page 60: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 61: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 62: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 63: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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.

Page 64: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 65: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 66: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 67: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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

Page 68: Understanding Postpartum Depression: The Role of the Pediatric Provider Samantha Meltzer-Brody, M.D., M.P.H. Director, Perinatal Psychiatry Program UNC.

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