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AN OVERVIEW OF PSYCHIATRIC DISORDERS DURING PREGNANCY AND

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AN OVERVIEW OF PSYCHIATRIC DISORDERS DURING PREGNANCY AND THE POSTPARTUM PERIOD John P Emerick MD January 15, 2009 Hormones and Affective Illness Well know ... – PowerPoint PPT presentation

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Title: AN OVERVIEW OF PSYCHIATRIC DISORDERS DURING PREGNANCY AND


1
AN OVERVIEW OF PSYCHIATRIC DISORDERS DURING
PREGNANCY AND THE POSTPARTUM PERIOD
  • John P Emerick MD
  • January 15, 2009

2
  • In 1858, one of the first papers to examine the
    effects of psychiatric illness during pregnancy
    was published by Marcé
  • Treatise on Madness in Pregnant Women
  • In 1980, the first International Conference was
    held by The Marcé Society, an international group
    formed to undertake the understanding, prevention
    and treatment of mental illness related to
    childbearing.
  • http//www.marcesociety.com/index.asp

3
Hormones and Affective Illness
  • Well know association between hormones and
    affective illness in women.
  • Peaks of female affective syndromes at puberty,
    menses and menopause
  • More women than men are effected by mood
    disorders
  • Significant hormonal changes occur during
    pregnancy

4
12 MONTH PREVALENCE OF SELECTED PSYCHIATRIC
ILLNESS IN WOMEN
5
ISSUES DURING PREGNANCY AND DELIVERY
  • MATERNAL

6
MATERNAL EFFECTS OF MDD DURING PREGNANCY
  • Effects upon motivation to remain healthly
    failure to gain weight, gain too much weight,
    poor compliance with medical treatment, nicotine
    and other substance abuse, TAB, etc
  • Re-emergence of severe MDD sx failure to
    function, potential suicide, etc

7
PSYCHIATRIC DISORDERS IN THE THIRD MONTH OF
PREGNANCY
  • with current prevalence
  • ANXIETY 21.7
  • MOOD 8.8
  • MDD 3.0
  • ALCOHOL 0.2
  • ANOREXIA 0.2
  • Borri, J Clin Psych 6910, October 2008
  • N 1066
  • Anxiety increased, including panic
  • Multiparity doubled the likelihood of having a
    mood d/o
  • Low socioeconomic status and multiparity
    associated with excess mood d/o
  • Low educational level associated with excess
    anxiety d/o

8
DEPRESSION IN HIGH RISK OBSTETRICAL PATIENTS
  • For uncomplicated pregnancy, best estimate point
    prevalence for MDD is 12.7
  • Of 129 patients admitted for high risk pregnancy,
    44 (55) scored 11 or gt on EPDS
  • Of these, 33 were evaluated with a SCID, which
    showed a diagnosis of MDD with 25 (75)
  • Overall prevalence of MDD was 25/129 or 19.4
  • Brandon J Clin Psych 694, April 2008

9
MDD PRIOR DIAGNOSIS MEDS AND PREGNANCY
  • N 201 women treated with AD for MDD and were
    euthymic at the start of pregnancy
  • During pregnancy, 43 (86) relapsed
  • Of the 82 women who continued AD, 26 relapsed.
  • Of the 65 women who stopped AD, 68 relapsed
  • HR5.0
  • CohenJAMA. 2006 Feb 1295(5)499-507.

10
DEPRESSION EFFECTS UPON POSTNATAL OUTCOME
  • Chung 2001
  • N959
  • Depression (BDI) increased risk for epidural
    anesthesia, operative and instrument deliveries
    and admits to NICU
  • Psychosomatic Medicine, 63, 2001
  • Alder 2007
  • Metanalysis of 35 studies
  • Depression and anxiety contribute independent of
    biomedical factors to adverse obstetric, fetal
    and neonatal outcomes.
  • J Matern Fetal Neonatal Med. 2007 Mar20(3)

11
From the current research, it appears that
affective disorders are very likely an
independent risk factor for adverse events during
pregnancy and delivery affecting the mother
12
ISSUES DURING PREGNANCY
  • FETAL

13
EFFECTS OF MDD ON FETUS
  • Lie evaluated 791 women at 10 weeks of gestation
    with the CESD. For preterm delivery the HR was
    1.6 if the CESDgt16. For a CESD gt22, HR was 2.2
  • Lie Human Reproduction, published online10-23-08
  • Field has published several studies providing
    evidence that MDD and dysthymia lead to low birth
    weight differentially and hypothesizing this is
    the result of elevated cortisol levels
  • Field Depress Anxiety. 200825(6)E11-6

14
EFFECTS OF AD ON FETUS 1
  • Suri study on AD and MDD. N93, 73 diagnosed
    with MDD. Monthly SCID evaluations were performed
    during pregnancy

Significant differences between group 1 and 2
and 1 and 3, but NS for group 2 and 3
15
EFFECTS OF AD ON FETUS 2
  • Suri study effects of AD dose
  • Suri A J Psychiatry, 1648, August 2007

16
EFFECTS OF AP DURING LATE PREGNANCY
  • 50 mothers and child with documented AP use to
    delivery. Olanzapine, risperdone, quietiapine and
    haloperidol studied.
  • Mean placental passage
  • olanzapine 72.1 N14
  • haloperidol 65.5 N13
  • risperdone 49.2 N6
  • quietiapine 23.8 N21
  • Exposure to olanzepine increased admits to NICU
    (30), 30 of infants weighed less than 2500
    grams, 21 were preterm, etc. However, NS.
  • Newton AJP 2007

17
PPHN
  • Persistent pulmonary hypertension of the newborn
  • Increased risk with SSRI after 20 weeks of
    gestation
  • Odds ration 6.1 for PPHN for those exposed late
    vs. no exposure or early exposure.
  • Chambers NEJM 2006

18
It appears that untreated MDD during pregnancy
and delivery exerts a negative effect upon the
fetus. However, successful treatment with ADs
(and perhaps certain APs) also has a risk of
negative effects. http//www.hfs.illinois.gov/ass
ets/091207_mch.pdf
19
PSYCHOTROPIC MEDICATIONS DURING PREGNANCY
20
PSYCHOTROPIC MEDICATIONS DURING PREGNANCY
  • Risk of maternal problems during pregnancy
  • Risk of gross malformation in fetus, and/or
    impact upon developing brain
  • Risk of psychiatric decompensation in mother
    during pregnancy and postpartum
  • Risk of danger during delivery to both mother and
    fetus ( low birth weight, prematurity, maternal
    bleeding, etc)
  • Risk of drug in breast milk for fetus
  • Risk of postpartum or longer effects upon
    neonate/infant/child development.

21
FDA RATINGS OF TERATOGEN RISK
  • This classification is set for an overhaul
  • Lithium is classified as Category C. However,
    clear link to Ebsteins abnormality.
  • All AED classified as Category C, except for
    valproate and carbamazepine which are Category D.
    However, all AED linked to increased risk of
    spinal defects
  • AED also linked to increased suicidal behavior
    and thoughts in all ages. (Risk is about double)
  • The FDA has not approved any AD or AP for use in
    pregnancy

22
FDA RATINGS OF TERATOGEN RISK
  • Category Description
  • A Adequate, well-controlled studies in pregnant
    women have not shown an increased risk of fetal
    abnormalities.
  • B Animal studies have revealed no evidence of
    harm to the fetus, however, there are no adequate
    and well-controlled studies in pregnant
    women. or Animal studies have shown an adverse
    effect, but adequate and well-controlled studies
    in pregnant women have failed to demonstrate a
    risk to the fetus.
  • C Animal studies have shown an adverse effect
    and there are no adequate and well-controlled
    studies in pregnant women. or No animal
    studies have been conducted and there are no
    adequate and well-controlled studies in pregnant
    women.
  • D Studies, adequate well-controlled or
    observational, in pregnant women have
    demonstrated a risk to the fetus. However, the
    benefits of therapy may outweigh the potential
    risk.
  • X Studies, adequate well-controlled or
    observational, in animals or pregnant women have
    demonstrated positive evidence of fetal
    abnormalities. The use of the product is
    contraindicated in women who are or may become
    pregnant.

23
ALTERNATIVE NON DRUG TREATMENTS
  • Bright light therapy (SAD)
  • Omega 3
  • Essential fatty acids
  • Interpersonal therapy

24
POSTPARTUM ISSUES
  • MATERNAL

25
POSTPARTUM DEPRESSION (PPD)
  • Depression in the postpartum period has been seen
    as a separate illness. Typical illness onset
    within first 6-8 weeks. Prevalence estimates vary
    from 10-20. Appears to be more frequent in AA
    and low socioeconomic status.
  • PPD is more frequent in women who have a prior Hx
    of affective illness. Vesqua A of Gen Psych
    2008
  • PPD is more common in women with an Axis II
    personality disorder diagnosis. Ackman Compr
    Psychiatry. 2007
  • Positive screening for PPD at day 5 may predict
    presence of PPD at 4 and 8 weeks. Adewudya Am J
    Psychiatry. 2006
  • PPD may become chronic without treatment.
    Goodman J Obstet Gynecol Neonatal Nurs.
    2004

26
DSM PPD SYNDROME
  • Onset within 4 weeks of delivery
  • Symptoms are same as non-post partum depression
    with additional issues about infant safety or
    impaired maternal bonding
  • Just like MDD, PPD can be either psychotic or
    non-psychotic.
  • Often comorbid anxiety disorder, including panic
  • Different than Baby Blues, which occurs by day 10
    in up to 70 of normal women

27
SCREENING FOR PPD
  • Edinburgh Postnatal Depression Scale (EPDS)
  • 10 questions, takes 3 minutes, can be
    administered via phone
  • Available in 23 languages
  • Compared to PHQ9 and PDSS, EPDS was significantly
    more accurate with a cutoff score to 10 or
    above.
  • Hanusa J Womens Health 2008

28
PPD TREATMENT
  • Only 9 decent RCT studies for all types of
    treatment
  • Most experts agree that SSRIs are effective, but
    only 1 RCT (fluoxetine)
  • For PPD, IPP may be just as effective (1 RCT)
  • ECT also judged to be effective.

29
PPD TREATMENT
  • Comparison trial of sertraline (sert) and
    nortriptyline (ntp)
  • 8 week acute phase, 6 month continuation
  • Doses 100mg for sert and 100mg for ntp
  • S/E burden similar

Wisner J Clin Psychopharm 2006
30
PDD TREATMENT
  • 8 week multicenter trial of Paxil (paroxetine)
    vs. placebo, new onset of MDD after, but within 3
    months of delivery
  • 71 women enrolled, 31 completed the trial
  • Minimum score of 16 on HAM-D
  • Results
  • Both groups improved significantly and did not
    differ on HAM_D or IDS-SR
  • Paroxetine noted to have a higher rate of
    remission 37 to 15
  • Yonkers J Clin Psych 2008

31
POSTPARTUM PSYCHOSIS
  • More malignant form of PPD vs. different
    disorder. Marked by delusions and hallucinations.
  • If prior PPP, risk of recurrence with each child
    is 30-50
  • Occurrence in 1 in 500 to 1 in 1000 deliveries,
    more common in primiparous
  • Risk of harm to newborn
  • Prior Hx of severe depression, BPAD,
    schizoaffective disorder or schizophrenia
  • Treatment antidepressants plus antipsychotics,
    ECT, etc

32
POSTPARTUM ISSUES
  • INFANT

33
INFANTICIDE AND POSTPARTUM PSYCHOSIS
  • The risk for homicide is 4x higher in the first
    year of life than at any other time.
  • Rate of infanticide in the USA is 8 per 100,000
    live births, in Wales 4.5/100,000
  • About half of cases, the motivation is to protect
    the child from intense suffering or a hopeless
    future (altruistic motivation)
  • Another group is driven by grandiose or
    persecutory delusions

34
WALES STUDY OF INFANT HOMICIDE
  • 112 perpetrators convicted from 1996-2001
  • Men accounted for 66, women for 34
  • Median age of perpetrator was 24
  • Of the infants murdered in the first year of
    life, 44 were killed in first 3 months of life
  • Mothers were more likely to kill in the first
    month of life (12 vs. 4 deaths)
  • Women committed neonaticide (within 24 hrs of
    birth) for 7 of 8 victims.
  • Women more likely to have psych dx, men more
    likely to have SUD
  • One third of perpetrators had a lifetime Hx of
    mental illness.

Flynn J Clin Psychiatry 2007
35
POSTPARTUM PSYCHOSIS AND ANTI-PSYCHOTICS
  • Rate of 1-2/1000 women, onset within 3 days in
    50
  • Most of the information are case reports, though
    a few studies determined levels in breast milk
  • Clozapine and olanzepine not currently thought to
    be as safe. (Gentile J Clin Psych 2008)
  • Continue breast feeding and stop AP vs. stop
    breastfeeding and continue AP

36
BREASTFEEDING AND ANTIDEPRESSANTS
  • Sertraline is most studied agent
  • Low concentration in breast milk/ not detectable
    in infants serum
  • Reasonable alternatives with similar safety
    profiles include paroxetine, fluvoxamine,
    mirtazapine and TCAs
  • Fluoxetine, venlafaxine and citalopram have
    higher concentrations in breast milk and can be
    detected in infants serum
  • If a prior Hx of response to a particular med,
    then consideration may be given to that med.

37
LATE EFFECTS OF PRESCRIPTION MEDS
  • New area of research
  • Long term studies to assess the impact upon brain
    development by drugs in utero
  • Obvious candidates are those drugs given to
    affect brain function AED, AD, AP, BZ, etc
  • Typically, no obvious birth defects
  • Recent article suggested a link between VPA and
    ASD

38
LATE EFFECTS
  • NEAD neurodevelopmental effects of antiepileptic
    drugs (USA and GB)
  • Ongoing study of 250 children to age 6 exposed in
    utero to valproic acid (VPA), carbamazepine (C),
    lamotrigine (L) and phenytoin (P)
  • Third year data

39
SUMMARY
  • Psychiatric disorders, especially depression,
    anxiety and psychosis, have significant effects
    on mother and child both during and after
    pregnancy
  • Medications used to treat maternal disorders have
    both positive and negative effects upon the
    mother, fetus, infant and may potentially effect
    the course of the childs development
  • Screening for these disorders is easily
    accomplished using the sensitive and specific
    Edinburgh Postnatal Depression Scale.
  • There remains much work to be done to define
    evidence based treatments and potential adverse
    treatment effects of these disorders.
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