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1
Postpartum Psychiatric Illness:
Early Detection, Treatment, and Prevention
Lee S. Cohen, M.D.
2
Admissions
Per Month
Risk of Psychiatric Illness During Pregnancy
and Postpartum Period
60
50
40
30
20
10
-2 Years
Pregnancy
-1 Year
Childbirth
+1 Year
+2 Years
Kendell et al. Br J Psychiatry. 1987;150:662
3
Spectrum of Postpartum Mood Disorders
Postpartum Psychosis
Postpartum
Symptom
Severity
Postpartum Depression
(10-15%)
Postpartum Blues
(50-85%)
None
4
Postpartum Blues
• 50-85% of women
• Within first two weeks after delivery
• Mood lability, tearfulness, anxiety and
sleep disturbance
• Minimal or no impairment of functioning
• Time limited
• No specific treatment required
5
Postpartum Depression
• Major and minor depression occurs in approximately
10% of women after live childbirth; range 5% to 15%14
• May have acute early onset (within days) but
symptoms typically emerge over time
(within 3 months postpartum)5
• Often underdiagnosed and undertreated5
• Significant risks to mother and child if left untreated6
1.
2.
3.
5.
O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171.
O’Hara MW, et al. J Abnorm Psychol. 1991;100:63-73.
Kumar R, Robson RM. Br J Psychiatry. 1984;144:35-47.
4.
Kendall K, et al. Br J Psychiatry. 1987;150:662-673.
Nonacs R, et al. J Clin Psychiatry. 1998;59(suppl 2):34-40.
6.
Lyons-Ruth. Harv Rev Psychiatry. 2000;8:148-153.
7.
Cogill SR, et al. Br Med J. 1986;292:1165-1167.
8.
Murray L, et al. Child Dev. 1996;67:2512-2526.
6
Puerperala Depression as a Distinct
Diagnostic Entity ?
• Prevalence of PPD is similar to non-puerperal MDD
• Similar clinical presentation
• Vulnerability to recurrent non-puerperal and puerperal
depression
• Similar response to antidepressant treatment
7
Psychiatric History Predicts Risk of Depression
in the Postpartum Period
60
Incidence (%)
50
40
30
20
10
0
Risk in general
population 1
History of major
depression 2
1.
2.
History of postpartum
depression 2
O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171.
O’Hara MW, et al. Postpartum Depression: Causes and
Consequences. New York, NY: Springer-Verlag; 1995.
8
Postpartum Anxiety Disorders
• Postpartum panic disorder
• Postpartum OCD : can be seen in the absence of PPD
• Comorbid depression and anxiety commo
9
PPD: Obsessions and Compulsions
• Intrusive obsessional thoughts common
• Thoughts of doing harm to infant
• Obsessions more common in PPD (57%) than in nonpuerperal MDD (36%)
Wisner et al, 1999
10
Postpartum Psychosis
• Rare, occurs in 1 to 2 per 1000 pregnancies
• Rapid, dramatic onset within first 2 weeks
• Resembles an affective (manic) psychosis
• Early signs: sleep disturbance, restlessness
• Depressed or elated mood, agitation, delusions,
depersonalization
• Risk of self-harm and harm to infant
11
What is the relationship between PPD
and Bipolar Disorder ?
12
Bipolarity in Postpartum Depression
• Increased risk for PPD in women with bipolar disorder
• Early age at illness onset
• Recurrent depressive episodes (>3)
• Brief episodes of MDD (<3 months)
• Hyperthymic personality
• Antidepressant-induced hypomania/mania
• Non-response to 3 or more antidepressants
Ghaemi et al, 2002
13
High Risk for Postpartum Psychosis Among Women
With Bipolar Disorder
• forme fruste of bipolar disorder
• Symptoms usually appear acutely within 48 hours
to 2 weeks after delivery
• Psychiatric emergency
• Estimated risk for bipolar patients is 20%–30%
(baseline risk in general population is 0.1%–0.2%)
Chaudron LH, et al. J Clin Psychiatry. 2003;64:1284-1292.
Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.
14
Postpartum Psychosis: Further Evidence for
a Bipolar Connection
• Family studies: postpartum psychosis
– Clusters in families multiply affected with bipolar
disorder
– Clusters in families multiply affected with
postpartum psychosis
• Genetic studies:
– Postpartum psychosis susceptibility linked to
variation at the serotonin transporter
Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.
Coyle N, et al. Lancet. 2000;356:1490-1491.
15
Longitudinal Course of Postpartum Psychosis
• 95 % affective psychosis
(bipolar disorder or schizoaffective disorder)
• 5 % schizophrenia
• Recurrence of affective episodes is the rule though
circumscribed illness may be seen
Terp et al, 1999
16
Postpartum Psychiatric Illness: Implications for
Early Detection
• Symptoms of postpartum depression may be difficult
to distinguish from normative postpartum symptoms
(sleep & appetite disturbance, loss of libido)
• Multiple contacts with health care providers
• PPD is frequently missed: role of obstetrician,
pediatrician
17
The MOTHERS Act (S. 1375)
Mom’s Opportunity to Access Help, Education, Research and
Support for Postpartum Depression Act
•
“To ensure that new mothers and their families are
educated about postpartum depression (PPD), screened
for symptoms, and provided with essential services, and to
increase research at the National Institutes of Health on
postpartum depression.”
•
Proposes to institute a program of grants to establish,
operate, and coordinate educational programs and health
care services
•
Current status: Bill has been referred to the Committee on
Health, Education, Labor, and Pensions
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Edinburgh Postnatal Depression Scale (EPDS)
• Screening tool for postpartum depression
• Validated in diverse populations
• 10-item self-rated questionnaire
• Score of > 12 suggestive of depression
• Suicidal ideation requires further evaluation
Cox et al, Br J Psychiatry 150:782-786.
19
Screening for PPD
• Screening and early intervention
– Most women not identified
– Goal is to screen women at highest risk
– Late identification increases risk
– What is the ideal screening tool?
Nonacs R, Cohen, L. Postpartum Psychiatric Syndromes. In: Sadock
B, Sadock A, ed. Comprehensive Textbook of Psychiatry. Philadelphia:
Lippincott Williams and Wilkins; 2000:1276-1283.
20
Postpartum Depression Predictors Inventory
Stronger Predictors:
• History of depression
• Depression in pregnancy
• Anxiety in pregnancy
• Stressful life events
• Marital dissatisfaction
• Child care stress
• Inadequate social supports
• Difficult infant temperament
• Low self-esteem
Weaker Predictors:
• Unwanted or
unplanned
pregnancy
• Lower
socioeconomic
status
• Being single
• Postpartum blues
21
Postpartum Mood Disorders:
Etiology
22
Psychosocial
Variables
PPD
Genetic
Vulnerability
Hormonal
Factors
23
Risk for PPD: Hormonal Factors
• Inconsistent findings
• Thyroid dysfunction is common in PPD
• No correlation with absolute concentrations of
gonadal steroid
• Behavioral sensitivity to gonadal steroids in women
with PPD
Bloch 2000
24
Postpartum Mood Disorders:
Treatment
25
Treatment of Depression in the Postpartum
Period: Psychotherapy
Treatment
Design
Results
RCT
• 12-wk IPT > wait-list controls
6
Open
• Significant  in depressive
symptoms from baseline
CBT3
(and fluoxetine)
87
RCT
• 6 sessions CBT >1 session CBT
• No significant advantage for
combination with fluoxetine
Counseling4
41
RCT
• 6 health nurse visits > controls
IPT1,2
n
120
IPT=interpersonal psychotherapy; CBT=cognitive behavioral
therapy;
1. O'Hara MW, et al. Arch Gen Psych. 2000;57:1039-1045.
 =decrease; RCT=randomized, controlled trial.
2. Stuart S, et al. J Psychother Pract Res. 1995;4:18-29.
3. Appleby L, et al. BMJ. 1997;314:932-936.
4. Wickberg B, Hwang CP. J Affect Disord. 1996;39:209-216.
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Postpartum Depression: Pharmacologic Treatment
Fluoxetine Appleby, 1997
Paroxetine Misri, 2004
Sertraline Wisner, 2006
Nortriptyline Wisner, 2006
Double-Blind
Double-Blind
Double-Blind
Double-Blind
Sertraline Stowe, 1995
Fluvoxamine Suri, 2002
Venlafaxine Cohen, 2001
Open
Open
Open
Bupropion Nonacs, 2004
Open
27
Venlafaxine for PPD: Treatment Response
5
25
25
20
20
4
15
15
3
**
10
10
*
5
5
0
0
Base Week 4 End
Ham-D
* = p<.0001
** = p<.0001
**
2
**
*
*
1
0
Base Week 4 End
Kellner Anxiety
* = p<.0001
** = p<.0001
Base Week 4 End
CGI
* = p<.0001
** = p<.0001
Cohen LS et al, 2001. J Clin Psychiatry 62:592-596.
28
Postpartum Depression:
Comparing Treatment Response
• Most studies on
100
• SSRIs and TCAs
have similar efficacy
• Bupropion may be
less effective
% of Patients
serotonergic agents
Response
Remission
80
60
40
20
0
SERT
OPEN
VEN
OPEN
BUP
OPEN
Stowe ZN, et al. Depression. 1995;3(49):55.
Cohen LS, et al. J Clin Psychiatry. 2001;62(8):592-596. Nonacs RM, Unpublished data.
29
Postpartum Depression: Pharmacologic Strategies
• Data to support use of serotonergic agents
(sertraline, fluoxetine, venlafaxine, fluvoxamine)
and TCAs (nortriptyline)
• Other antidepressants may be effective
• Adequate dosage
• Adequate duration of treatment (>6 months)
• Adjunctive anxiolytic agents (lorazepam, clonazepam)
30
Treatment of Bipolar Depression During the
Postpartum Period
• No treatment studies in literature
• Mood stabilizers (lithium, lamotrigine)
• Atypical anti-psychotics may be helpful
• Antidepressants may exacerbate mood and should be
used with caution
31
Postpartum Depression: Is there a Role for
Hormonal Treatment ?
• Progesterone:
Inconsistent findings
• Progesterone may exacerbate mood symptoms ?
• Estrogen: Beneficial alone or as adjunct to
antidepressant
Gregoire 1996, Ahokas 2001
32
Estrogen for Postpartum Depression
• 61 women with PPD (37 active, 24 placebo)
• Transdermal 17 -estradiol
• 47% on antidepressants at study entry
• Treatment effect within 1st month, estrogen
decreased EPDS by 4.38 points at 12 wks
• At 12 wks, 80% on estrogen no longer depressed
(<14 on EPDS) vs. 31% in placebo group
• No evidence of uterine hyperplasia
Gregoire, 1996
33
Estrogen for Postpartum Depression
• 23 women with PPD (mean MDRS 40.7)
• All women with low serum estradiol
(mean 79.8 pmol/L)
• Sublingual 17 -estradiol
• After 2 wks, 19/23 (83%) with clinical recovery (mean
MDRS 11.0)
Ahokas, 2001
34
Postpartum Psychosis: Treatment
• Psychiatric /Obstetric emergency
• Treat as an affective psychosis (antipsychotic (
atypical/typical), mood stabilizer, benzodiazepines)
• ECT is rapid and effective
• Duration of treatment not well established
• Need for maintenance treatment in patients with
recurrent affective disorder
35
Psychotropic Medications in
Breast-Feeding Mothers
36
Psychotropic Medications and Breast-Feeding
• About 50% of women nurse their infants
• Benefits: nutrition, immunity, cognitive development
• All medications are secreted in breast milk
• Concentrations in breast milk vary
• Adverse events in infant are rare
• Decisions made on a case by case basis
37
Which Antidepressant is the Best ?
The one that is likely to work the best
• Continue antidepressant used during pregnancy
• Use agent to which patient has responded
to in the past
• Sertraline, paroxetine, nortriptyline well-characterized,
no adverse events
38
Prevention of Postpartum Illness
39
Identification of women at high risk for
postpartum psychiatric illness
Is this disorder preventable?
40
Stratification of Risk
LOW
No history
Routine
Hx of MDD
Consider Prophylaxis
Hx of PPD OR
Antidepressant
Recurrent Severe MDD
Prophylaxis
Hx of Bipolar Disorder
Intense Monitoring
OR
PP Psychosis
HIGH
AND
Li Prophylaxis
41
Risk of Relapse Following Lithium Discontinuation
Postpartum
(Weeks 41–64)
% Remaining Stable
Pregnancy
(Weeks 1–40)
100
90
80
70
60
50
40
30
20
10
0
(n=25)
(n=42)
(n=59)
(n=20)
Nonpregnant
Pregnant
Nonpregnant
Postpartum
0 4 8 12 16 20 24 28 32 36 40 44 48
Weeks at Risk Off Lithium
52
56
60
64
Viguera AC. Am J Psychiatry. 2000;157:179-184.
42
Non-Pharmacologic Prophylaxis
• Positive effect of IPT during pregnancy
– 13 women with depression during pregnancy
– IPT induced remission in all
– No women developed PP
Spinelli 1997
43
Pharmacologic Prophylaxis: Postpartum
Major Depression
• Antidepressant treatment in women with
history of PPD: equivocal results
– Open study with TCAs and SSRIs showed reduction in
risk
(Wisner 1994)
– Placebo-controlled study with NTP negative
(Wisner 1999)
– Placebo-controlled study with sertraline positive
(Wisner 2004)
44
Depression in Women Treated with Postpartum
Sertraline or Placebo
• Non-depressed women
with hx of PPD (n=22)
• Randomized to sertraline
(up to 75mg) or placebo
• Drug started after delivery
• Drug tapered at week 17
Wisner KL et al, 2004. Am J Psychiatry 161:1290-1292.
45
Postpartum Prophylaxis for Women with
Bipolar Disorder
46
Postpartum Lithium Prophylaxis
for Bipolar Women
Subjects (Dx)
Lithium
benefit
Austin, 1992
Puerperal psychosis/
Bipolar disorder
+
Van Gent, 1992
Bipolar disorder
+
Abou-Saleh, 1983
Bipolar disorder
Unipolar depression
+
Stewart et al, 1991
Mixed diagnoses
+
Cohen et al, 1995
Bipolar disorder
+
47
Postpartum Prophylaxis with Mood Stabilizers
other than lithium
Wisner, 2004
Sharma , 2006
Subjects (Dx)
Benefit
Bipolar disorder
Valproate +/-
Puerperal
psychosis/Bipolar
disorder
olanzapine +
Wisner KL et al Biol Psychiatry 2004;56:592-596;
Sharma V et al. Bipolar Disord 2006;8:400-4
48
Cumulative Survival
Postpartum Prophylaxis in Bipolar Women
Prophylaxis (N=14)
No Prophylaxis (N=13)
Time (Weeks)
Significant difference between groups
(Peto-Peto-Wilcoxen 2=6.966, df=1,p<0.01)
Cohen LS, Sichel DA, et al. Am J Psychiatry. 1995.
49
Postpartum Mood Disorders:
Long Term Impact
50
Impact of Maternal Depression on Child Well-Being
• Delays in cognitive development
• Increased risk of behavioral problems
– Infants: sleep problems
– Toddlers: temper tantrums
– School age: anxiety, inattention, hyperactivity,
aggression, poor school performance
• Insecure attachment, emotional dysregulation
• Risk for child abuse and neglect
Atkinson L et al. Clin Psychol Rev. 2000;20:1019-1040.
Murray L, Cooper PJ. Arch Dis Child. 1997;77:99-101.
51
Impact of Postpartum Depression (PPD) on
Cognitive Functioning
• Cohort of mothers recruited at 2 months postpartum
(Cambridge, England)
• At 18 months, children of mothers with PPD
more likely than children of well mothers to have
cognitive delays
• At 5 years, no differences between 2 groups
• Other studies in disadvantaged populations show
persistence of cognitive deficits, especially in boys
Murray L. J Child Psychol Psychiatry. 1992;33:543-561.
Cogill SR et al. BMJ. 1986;292:1165-1167.
Sharp D et al. J Child Psychol Psychiatry. 1995;36:1315-1336.
52
PPD: Long-Term Effects on IQ and
Cognitive Function
• 148 women enrolled at 3
months postpartum
• Children (n = 132)
assessed at 11 years
• Lower IQ
• Attention, mathematical
reasoning deficits
• Conduct problems
• Outcomes worse in
children exposed to
recurrent MDD (although
exposure to one episode of
MDD had negative effects)
Hay DF et al. J Child Psychol Psychiatry. 2001;42:871-889.
53
Summary
• Postpartum psychiatric illness is common
• Untreated illness has significant impact on child
development and well-being
• Effective non-pharmacologic and pharmacologic
treatments
• Early treatment is associated with better prognosis
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