Transcript *Goals:

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
cortisol
cortisol
• ALSPAC community
sample
– n=8,323 mother-infant
pairs
– Gestational Age: 32 weeks
– Behavioral problems at 4
and 7 years
(Glover V, 2003,BJM) )
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 malformations
o +/- 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
Discontinued
Maintained
Relapse
44/65 (68%)
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
Mean Depression Scores
30
SIGH-SAD
HAM-D
25
20
15
10
5
0
0
1
2
3
Weeks of Light Therapy
Oren D, Wisner K, Spinelli M et al, 2002
4
5
There are no clinical guidelines
for effective treatment for
antepartum depression.
Interpersonal Psychotherapy for
Antepartum 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 Women
EPDS >>>more depressed
Edinburgh Postnatal Depression Scale
(
p=.005)
22
PEP
IPT-P
20
18
16
14
12
10
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16
IPT-P Phase
IPT-P vs. PEP in Depressed Pregnant Women
Mean HAM-D
(p=.021)
26
PEP
IPT-P
24
22
HAM-D
20
18
16
14
12
10
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16
IPT-P Phase
Clinical Global Impressions
Recovery < 2
(P=.O11)
60
Frequency (%)
50
40
30
20
10
0
IPT-P
PEP
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
• Behavior Problems,
Delayed Language
• Easily Angered
–
• Insecure Attachment,
Irritable
– (Biringen and Robinson,
1991; Zuckerman et al,
1990)
(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 trial
 Sertraline (Zoloft); open
 Venlafaxine (Effexor): open
 Interpersonal Psychotherapy
 Fluoxetine 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 Breastfeeding
Provides immunity
Allergies, asthma
Otitis 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 PSYCHOSIS
HIPPOCRATES 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
• cognitive disorganization
• visual, tactile and olfactory hallucinations
• bizarre behavior
• self-neglect
Waxing 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
Estrogen  TRYP
5HT
5HT Re-uptake Site
E2 
PROG

MAO / COMT
MAO: Monoamine Oxidase
COMT: Catechol-O-Methyl
Transferase
E2  MAO & COMT   5HT
PROG  MAO & COMT  
SHT
Hypothalamic Pituitary Ovarian Axis
(HPO)
Brain
Brain
5HT
EPI
DA
placenta
progesterone
thyroid
prolactin
estrogen
cortisol, androgen
hCG, hPL, LH, FSH
SPIRAL INTO MENTAL ILLNESS
(Denno, 2003)
•PPD, VH
PREGNANCY 1
PPD, D/C JOGGING,
SWIMMING, SOCIAL WD
PREGNANCY 2
PREGNANCY 3
PREGNANCY 4
PREGNANCY 5
MEDS: HALDOL,
REMERON, EFFEXOR
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**
SERIES OF ERRORS…….
(Denno, 2003).
PH, FH PSYCH
•BPD: FATHER, BROTHER
MDD: MOTHER, SISTER ,
BROTHER
H/O CHILDBIRTH
1994-2001: PREGNANT OR
LACTATING
ISOLATION AND
PSYCHOSOCIAL
STRESSORS
•HOMESCHOOLING; BIBLE
STUDY ETC.
STIGMA AND EDUCATION
PROFESSIONAL
•COUPLE, FAMILY, NEIGHBORS
•PSYCHIATRY, CHILD SERVICES,
LEGAL COMMUNITY
SOCIETY’S FAILURE
MEDICAL
MANAGEMENT
•MEDICATION, SAFETY
HOSPITAL
•MD, NURSES, HMO
ARCHAIC LAWS
JUDICIAL SYSTEM
DEATH PENALTY JURY
JURY ? TREATMENT
PUBLIC EDUCATION
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…...