ANTEPARTUM DEPRESSION

• 10 - 13% : Major and Minor Depression• (O’Hara, 1990; Gotlib et al, 1989; Kumar 1984,

Evans et al 2001)

• Low SES and psychosocial stressors• (Hopfer et al 1995)

• Strongest Predictor of PPD• (Graff et al, 1991)

Psychiatric Disorders during Pregnancy and the Postpartum

Period

Margaret Spinelli, MD

Associate Prof Of Psychiatry

Director, Maternal Mental Health Program

ANTEPARTUM DEPRESSION

• Poor Appetite; Weight

• Insomnia

• Poor Prenatal Care

• Nicotine, Drugs and Alcohol

(Zuckerman et al, 1990)

ANTEPARTUM DEPRESSION

• Low birth weight• Prematurity• Growth retardation• Small for gestational age infants• Developmental delay

• (Flynn 2005; Bonari et al 2004; Kurki et al 2000; Zuckerman et al, 1990; )

PRENATAL DEPRESSION AND ANXIETY

ANXIETY>>>>> UTERINE ARTERY

RESISTANCE >>>>

• LOW BIRTH WEIGHT • INCREASED MISCARRIAGE• PREMATURITY• FETAL HYPOXIA

– (Glover and O’Connor 2002, Chung et al 2001, Wadhwa et al 1993 Teseira et al. 1999)

Antenatal Anxiety: effects on the fetus and child

• ALSPAC community sample – n=8,323 mother-infant

pairs

– Gestational Age: 32 weeks

– Behavioral problems at 4 and 7 years

(Glover V, 2003,BJM) )

cortisol

cortisol

DECISION ANALYSIS

RISK / BENEFIT ANALYSIS

• framed by clinician’s expertise and the patient’s values and treatment preferences

• **PLAN BEFORE PREGNANCY**• (Wisner et al 2000)

Antidepressant SSRIs: metanalysis

 o Sertraline (Zoloft)

o Citalopram (Celexa)

o Fluoxetine (Prozac)

o no major malformationso +/- Neonatal toxicity

(Sivojelezova et al; 2005)

PAXIL

• Retrospective Epidemiological Study– 3,581 SSRI exposed pregnant women

• increased risk of major congenital malformations

– (OR 2.20; 95% CI: 1.34-3.63)

• increased risk for cardiovascular malformations– (OR 2.08; 95%CI: 1.03-4.23)

– Ventricular Septal Defect. (10/14)• (GSK: 2005)

TRICYCLICS (TCAs)

• Desipramine (DMI)

• Nortryptylline(NTP)

– Serum levels

– Neonatal toxicity +/-• Withdrawal sx.

• Anticholinergic effects

Neurodevelopment: TCA or SSRIs through fetal life

Mother- child pairs (15-71 mos.): Tricyclics: (n = 46) Fluoxetine: (n = 40) Control: (n = 36)

Results: TCA or SSRI:– NO difference in IQ (Baylor or Mc Carhty scales),– temperament, language, or behavior

Depression: duration>>>> low IQ episodes>>>> poor language development

– Nulman et al 2002

“Neonatal Withdrawal Syndrome” Databases of adverse drug events

• WHO Collaborating Center for Drug Monitoring– ID 74 Cases of “Neonatal Withdrawal Syndrome”– tremor, neonatal convulsions, abnormal crying

• (paroxetine (n=51), fluoxetine (10), sertraline (7), citalopram (6), venlafaxine (6)

• (Sanz et al; The Lancet, 2005)

• FDA Adverse Event Reporting System – 57 cases of neonatal withdrawal

– (paroxetine (n=35), fluoxetine (4), sertraline (8), citalopram (5), venlafaxine (3), fluvoxamine (2)

(CDER: 2004, meeting document)

SSRI Neonatal WD: Case Reports• 18 cases of SSRI

– 61% Paxil; 22% Prozac

• Exposure– (17-40 weeks gestation; median 40 wks)

• Onset of symptoms:– Tremor, increased muscle tone, irritability, resp distress

• birth to 3 weeks

• Duration of symptoms:• mean: 2 weeks

• SSRIs:– (paroxetine (n=11), fluoxetine (4), sertraline (1), citalopram (1),

venlafaxine (1)• (Moses-Kolko et al; JAMA, 2005)

Meta-analysis: 3rd TM exposure to SSRIs

• Neonatal Behavioral Syndrome;– Meta-analysis: 3rd TM: ( 9 cohort studies and 18 cases)

– Risk Ratio : 3.0 (95% CI, 2.0-4.4)– CNS, motor, respiratory and GI signs – Usually mild and time limited (2 weeks)– Managed with supportive care – Most involve fluoxetine and paroxetine– More severe: seizures, hyperpyrexia etc.

• (Moses-Kolko et al. JAMA, 2005)

Neonatal Adaptation after 3rd TM exposure to SSRIs

Neonatal Behavioral Syndrome;Special Care Nursery Admissions:

2.6 (95% CI, 1.4-4.7)

Overall respiratory difficulty:

2.3 (95% CI, 1.6-3.2)

– Incidence of Intubation: 0.3% (1/313)

– No neonatal deaths

• (Moses-Kolko et al. JAMA, 2005)

SSRIs and Persistent Pulmonary Hypertension of the Newborn

377 Infants born with PPHN

14 infants with late (>20 weeks) SSRI exposure were compared to

6 control infants with early (<20 weeks) or no exposure to SSRI.

Odds of PPHN with late exposure compared to early or no exposure :

6.1 (95% CI, 2.2-16.8)(Chambers et al, NEJM, 2006)

Absolute Risk of PPHN

• Limitations:– supports association; no cause effect relationship– small Ns– retrospective

RR = 6.1 (95% CI, 2.2-16.8)

Absolute Risk = 6-12/ 1000 births (0.6-1.2%)

Therefore 99% of women treated with an SSRI delivered infants without PPHN

How should these reports

impact clinical practice?

Recurrence Risk of MDD in women who discontinue antidepressant treatment

proximal to conception

Group Relapse

Discontinued 44/65 (68%)

Maintained 21/82 (25%)

Time to recurrence:

50% in 1st TM / 90% in 2nd TM(Cohen et al; JAMA, 2006)

ELECTROCONVULSIVE

THERAPY

• APA guidelines:

– Ob consult

– Gest age >10 weeks

– Maternal and fetal heart rate

– Ob present if high risk

– Faculties for fetal emergencies

– Monitor fetal movement

Herbals

NO CLINICAL DATA – St John’s Wort– SAMe– Valerian Root

+/-– Omega 3 Fatty Acids

Alternatives

• Acupuncture • (n=61)

• Active acupuncture, v. control acupuncture vs. massage

• Response rates 69% v.47% v.29%• (Manber et al 2004)

• VNS

Light Therapy for Pregnant Depressed Women

0

5

10

15

20

25

30

0 1 2 3 4 5

SIGH-SADHAM-D

Oren D, Wisner K, Spinelli M et al, 2002

Me

an

Dep

res

sio

n S

co

res

Weeks of Light Therapy

There are no clinical guidelines for effective treatment for

antepartum depression.

Interpersonal Psychotherapy forAntepartum Depression

(IPT-P)

(Spinelli and Endicott Am J Psychiatry 2003, 160:555-562)

NIMH Grant #1K20 MH01276-01

DEMOGRAPHICS(N=38)

AGE: 29.I0 ( + 6.20)GESTATION: 21.40 WKS. ( +7.20)INCOME:

• 50 % $5-25,OOO• 16% $25-40,000

RACE: LATINO : 66% ( 80% SPANISH SPEAKING) AFRICAN AMERICAN: 5% CAUCASIAN: 29%

IPT-P vs. PEP in Depressed Pregnant WomenEdinburgh Postnatal Depression Scale

(p=.005)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

10

12

14

16

18

20

22

IPT-P Phase

EP

DS

>>

>m

ore

dep

ress

ed

PEP IPT-P

IPT-P vs. PEP in Depressed Pregnant WomenMean HAM-D

(p=.021)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1610

12

14

16

18

20

22

24

26

IPT-P Phase

HA

M-D

PEPIPT-P

Clinical Global Impressions Recovery < 2

(P=.O11)

IPT-P PEP0

10

20

30

40

50

60

Fre

que

ncy

(%)

ANTEPARTUM INTERPERSONAL

PSYCHOTHERAPY AT 3 NEW YORK CITY SITES

NIMH Grant #RO1 MH 069915-01A2

DESIGN AND METHODS

NIMH 5 Year Clinical Treatment Trial

• Focus: Psychiatry into primary care– Treatment in OB department

• 3 NYC sites• 3 MFM faculty: co-PIs

– Dr. Jane Cleary-Goldman (Columbia)– Dr. Robin Kalish (Cornell)– Dr. Lois Brustman (St.Luke’s Roosevelt Hospital)

AIM

Assess the efficacy of a 12-week

bilingual treatment trial of

Interpersonal Psychotherapy for Antepartum Depression

vs. Parenting Education Program

for multi- ethnic/racial sample from 3 NYC sites

Antepartum Interpersonal Psychotherapy at 3 NYC Sites

• detect and treat antepartum depression

• prevent postpartum depression

• assess maternal fetal/ infant attachment

• evaluate feasibility of services as they relate to race, ethnicity and SES ($50/visit)

WHEN BONDING FAILS..

Depressed mother; Depressed child

• Poor Response to Infant Cues/ Lack of Warmth

• Insecure Attachment, Irritable

– (Biringen and Robinson, 1991; Zuckerman et al, 1990)

• Behavior Problems, Delayed Language

• Easily Angered– (Murray, 1991; Biringen and Robinson,

1991)

• Intellectual Deficits, Predisposition to Depression

– (Cogill et al, 1986;– Weissman et al, 1987)

Epidemiology of Postpartum Episodes

Postpartum Depression Prevalence: 10-20%

Across cultures (Kumar 1994)

Risk Factors: Personal and Family H/O depression

Prenatal depression**

Prominent symptoms: anxiety associated with distressing thoughts about infant safety Feelings of guilt and inadequacy about mothering Inability to sleep when infant sleeps lack of interest in baby, family or activities anxiety as bizarre thoughts and fears poor bonding, feel “detached” “numb” Thoughts of death or suicide

(DOH;OMH 2005; Flynn, 2005)

)

Treating Postpartum Depression

Fluoxetine (Prozac): Controlled trialSertraline (Zoloft); openVenlafaxine (Effexor): open Interpersonal PsychotherapyFluoxetine and CBT

Guidelines for Medicating during Lactation

• Avoid polypharmacy

• Monitor infant sleep, feeding

• Bottle feed if sick

• Lowest effective dose

• Collaboration with Pediatrician

• All pass to breast milk

– depends on drug and metabolite

– UK outcome on physiology, behavior and development

Benefits of BreastfeedingProvides immunity

Allergies, asthmaOtitis media

Viral diarrhea

RSV morbidity

Upper and lower respiratory infection

Childhood lymphoma, Type I DM, Crohn’s

IQ: 8-12 points

BREASTFEEDING AND ANTIDEPRESSANTS

• SSRIs: first line – Few adverse effects to date

– Infant serum: minimal or no drug or metabolite***

• TCAs: second line– NTP (least detected in infant serum)

– Limitations:• Small Ns, case reports, no long term effects

• ***does not apply to fluoxetine/ venlafaxine

BREASTFEEDING AND ANTIDEPRESSANTS

Celexa: Elevated infant levels

‘uneasy sleep”

Serum Fluoxetine accumulation long T ½: accumulation in infant serum

Immature infant enzymes

Irritability

BREASTFEEDING AND ANTIDEPRESSANTS

Sertraline

usually yields undetectable infant serum levels

No adverse effects

Maternal 5HT concentration decreased with sertraline but infant platelet 5HT transport not affected c/w undetectable levels in infant serum.

• (Epperson 2003)

BENZODIAZEPINES AND LACTATION

• Neonatal Risks (Burt et al. AJP 2001)

– withdrawal, sedation, cyanosis

• Guidelines– low dose, monotherapy– split dosing– discard feeding at peak drug level; – formula supplementation– short-acting, low metabolites

• Alternative:– Nortryptylline (NTP)

POSTPARTUM PSYCHOSIS

auditory hallucinations (baby; religious) visual hallucination (seeing or feeling a presence) agitation, irritability paranoid delusions delirium (waxing and waning) confusion mania suicidal or infanticidal thoughts bizarre delusions

POSTPARTUM PSYCHOSISHIPPOCRATES 4TH CENTURY “LACTATIONAL PSYCHOSIS”

PREVALENCE– 1-2/1000– 70% IN THE FIRST 2 WEEKS– BIPOLAR EPISODE ****– (<5% SCHIZOPHRENIA)

QUALITIES– ORGANIC SYMPTOMS – WAXING & WANING/ AMNESIA

RISK: INFANTICIDE RECURRENCE: 30-50%

“PROPHYLAXIS”: PP LITHIUM OR OTHER

““Cognitive Disorganization/Psychosis”(PPP)

(Wisner et al; 1994)

• delirium; Impaired Sensorium delirium; Impaired Sensorium

• cognitive disorganizationcognitive disorganization

• visual, tactile and olfactory hallucinationsvisual, tactile and olfactory hallucinations

• bizarre behavior

• self-neglectWaxing and waning presentation

***Psychiatric emergency***

PPP is BPD?? (Chaudron 2003)

• Bipolar women– high risk for postpartum episode

– (Liebenluft ‘96)

– highest rates of PPP in general population– (Jones and Craddock 2001, Reich and Winokur, 1970)

– high rates of PP relapse– (Marks et al, 1992, Dean et al. 1989)

– FH of PPP– (Jones and Craddock 2001, Reich and Winokur, 1970,

Dean et al, 1989))

NEUROHORMONES & CNS

E2 PROG MAO / COMT

E2 MAO & COMT 5HT

PROG MAO & COMT SHT

MAO: Monoamine Oxidase

COMT: Catechol-O-Methyl Transferase

Estrogen TRYP

5HT Re-uptake Site5HT

Hypothalamic Pituitary Ovarian Axis (HPO)

Brain 5HT

EPI

DA

Brain

placenta

estrogencortisol, androgenhCG, hPL, LH, FSH

progesterone thyroid prolactin

PREGNANCY 3 PREGNANCY 4

PREGNANCY 5

SPIRAL INTO MENTAL ILLNESS(Denno, 2003)

PREGNANCY 1

MEDS: HALDOL, REMERON, EFFEXOR

PREGNANCY 2

•PPD, VH

PPD, D/C JOGGING, SWIMMING, SOCIAL WD

PPP: 2 HOSPITALIZATIONS: PSYCHOSIS AND SUICIDE, “DESPONDENT,” DISCHARGE BECAUSE OF INSURANCE

PPP: 2 HOSPITALIZATIONS, “CATATONIC” 24 HOUR WATCH

•JUNE 6, 2001: HALDOL D/Cd, EFFEXOR, REMERON 40 MG/D

•**NO MOOD STABILIZER**

ISOLATION AND PSYCHOSOCIAL

STRESSORS

STIGMA AND EDUCATION

SERIES OF ERRORS…….(Denno, 2003).

PH, FH PSYCH

PROFESSIONAL

H/O CHILDBIRTH

•BPD: FATHER, BROTHER MDD: MOTHER, SISTER , BROTHER

1994-2001: PREGNANT OR LACTATING

•HOMESCHOOLING; BIBLE STUDY ETC.

•COUPLE, FAMILY, NEIGHBORS

•PSYCHIATRY, CHILD SERVICES, LEGAL COMMUNITY

HOSPITAL

JUDICIAL SYSTEM

SOCIETY’S FAILUREMEDICAL

MANAGEMENT

PUBLIC EDUCATION

•MEDICATION, SAFETY

•MD, NURSES, HMO

ARCHAIC LAWS

DEATH PENALTY JURY

JURY ? TREATMENT

FAMILY: MENTAL HEALTH

NEIGHBOR: “CAGED ANIMAL”

‘The infant's life is a vulnerable thing and depends

to a great extent on the mother's good will. Sara

Ruddick (1989) has captured the contradictions

well in noting that mothers, while so totally in

control of the lives and well being of their infants

and small babies, are themselves under the

dominion and control of others…...