Postpartum Psychiatric Illness:
Early Detection, Treatment, and Prevention
1
Lee S. Cohen, M.D.
Risk of Psychiatric Illness During Pregnancy
and Postpartum Period
2
Kendell et al. Br J Psychiatry. 1987;150:662
Admissions
Per
Month
60
50
40
30
20
10
-2 Years -1 Year Childbirth +1 Year +2 Years
Pregnancy
Spectrum of Postpartum Mood Disorders
3
Postpartum Psychosis
Postpartum
Symptom
Severity
Postpartum Depression
(10-15%)
None
Postpartum Blues
(50-85%)
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
4
Postpartum Depression
• Major and minor depression occurs in approximately
10% of women after live childbirth; range 5% to 15%1-4
• 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
5
1. O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171.
2. O’Hara MW, et al. J Abnorm Psychol. 1991;100:63-73.
3. Kumar R, Robson RM. Br J Psychiatry. 1984;144:35-47.
4. Kendall K, et al. Br J Psychiatry. 1987;150:662-673.
5. 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.
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
6
Psychiatric History Predicts Risk of Depression
in the Postpartum Period
7
1. O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171.
2. O’Hara MW, et al. Postpartum Depression: Causes and
Consequences. New York, NY: Springer-Verlag; 1995.
0
10
20
30
40
50
60
Risk in general
population 1
History of major
depression 2
History of postpartum
depression 2
Incidence
(%)
Postpartum Anxiety Disorders
• Postpartum panic disorder
• Postpartum OCD : can be seen in the absence of PPD
• Comorbid depression and anxiety commo
8
PPD: Obsessions and Compulsions
• Intrusive obsessional thoughts common
• Thoughts of doing harm to infant
• Obsessions more common in PPD (57%) than in non-
puerperal MDD (36%)
9
Wisner et al, 1999
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
10
What is the relationship between PPD
and Bipolar Disorder ?
11
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
12
Ghaemi et al, 2002
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%)
13
Chaudron LH, et al. J Clin Psychiatry. 2003;64:1284-1292.
Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.
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
14
Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.
Coyle N, et al. Lancet. 2000;356:1490-1491.
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
15
Terp et al, 1999
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
16
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
17
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
18
Cox et al, Br J Psychiatry 150:782-786.
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?
19
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.
Postpartum Depression Predictors Inventory
20
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
Postpartum Mood Disorders:
Etiology
21
22
Psychosocial
Variables
Genetic
Vulnerability
Hormonal
Factors
PPD
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
23
Bloch 2000
Postpartum Mood Disorders:
Treatment
24
Treatment of Depression in the Postpartum
Period: Psychotherapy
25
1. O'Hara MW, et al. Arch Gen Psych. 2000;57:1039-1045.
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.
Treatment n Design Results
IPT1,2
120 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
IPT=interpersonal psychotherapy; CBT=cognitive behavioral therapy;
 =decrease; RCT=randomized, controlled trial.
Postpartum Depression: Pharmacologic Treatment
Fluoxetine Appleby, 1997 Double-Blind
Paroxetine Misri, 2004 Double-Blind
Sertraline Wisner, 2006 Double-Blind
Nortriptyline Wisner, 2006 Double-Blind
Sertraline Stowe, 1995 Open
Fluvoxamine Suri, 2002 Open
Venlafaxine Cohen, 2001 Open
Bupropion Nonacs, 2004 Open
26
Venlafaxine for PPD: Treatment Response
27
Cohen LS et al, 2001. J Clin Psychiatry 62:592-596.
Ham-D
* = p<.0001
** = p<.0001
0
Kellner Anxiety
* = p<.0001
** = p<.0001
1
2
3
4
5
0
CGI
* = p<.0001
** = p<.0001
5
10
15
20
25
0
Base End
Week 4
**
*
Base End
Week 4 Base End
Week 4
**
*
**
*
5
10
15
20
25
Postpartum Depression:
Comparing Treatment Response
• Most studies on
serotonergic agents
• SSRIs and TCAs
have similar efficacy
• Bupropion may be
less effective
28
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.
0
20
40
60
80
100
SERT
OPEN
VEN
OPEN
BUP
OPEN
Response
Remission
%
of
Patients
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)
29
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
30
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
31
Gregoire 1996, Ahokas 2001
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
32
Gregoire, 1996
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)
33
Ahokas, 2001
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
34
Psychotropic Medications in
Breast-Feeding Mothers
35
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
36
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
37
Prevention of Postpartum Illness
38
39
Identification of women at high risk for
postpartum psychiatric illness
Is this disorder preventable?
Stratification of Risk
40
No history Routine
Hx of MDD Consider Prophylaxis
Hx of PPD OR Antidepressant
Recurrent Severe MDD Prophylaxis
Hx of Bipolar Disorder
OR
Intense Monitoring
AND
PP Psychosis Li Prophylaxis
LOW
HIGH
Risk of Relapse Following Lithium Discontinuation
41
Viguera AC. Am J Psychiatry. 2000;157:179-184.
40 44 48 52 56 60 64
0
10
20
30
40
50
60
70
80
90
100
0 4 8 12 16 20 24 28 32 36
Weeks at Risk Off Lithium
%
Remaining
Stable
Pregnancy
(Weeks 1–40)
Postpartum
(Weeks 41–64)
Nonpregnant
Postpartum
Nonpregnant
Pregnant
(n=42)
(n=59)
(n=20)
(n=25)
Non-Pharmacologic Prophylaxis
• Positive effect of IPT during pregnancy
– 13 women with depression during pregnancy
– IPT induced remission in all
– No women developed PP
42
Spinelli 1997
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)
43
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
44
Wisner KL et al, 2004. Am J Psychiatry 161:1290-1292.
Postpartum Prophylaxis for Women with
Bipolar Disorder
45
Postpartum Lithium Prophylaxis
for Bipolar Women
46
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
Postpartum Prophylaxis with Mood Stabilizers
other than lithium
47
Wisner KL et al Biol Psychiatry 2004;56:592-596;
Sharma V et al. Bipolar Disord 2006;8:400-4
Subjects (Dx) Benefit
Wisner, 2004 Valproate +/-
Bipolar disorder
Sharma , 2006
olanzapine +
Puerperal
psychosis/Bipolar
disorder
Postpartum Prophylaxis in Bipolar Women
48
Cohen LS, Sichel DA, et al. Am J Psychiatry. 1995.
Significant difference between groups
(Peto-Peto-Wilcoxen 2=6.966,
df=1,p<0.01)
Cumulative
Survival
Time (Weeks)
Prophylaxis (N=14)
No Prophylaxis (N=13)
Postpartum Mood Disorders:
Long Term Impact
49
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
50
Atkinson L et al. Clin Psychol Rev. 2000;20:1019-1040.
Murray L, Cooper PJ. Arch Dis Child. 1997;77:99-101.
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
51
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.
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)
52
Hay DF et al. J Child Psychol Psychiatry. 2001;42:871-889.
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
53
www.womensmentalhealth.org
54

Postpartum-Mood-Disorders-PPT.-Cohen-MD.ppsx

  • 1.
    Postpartum Psychiatric Illness: EarlyDetection, Treatment, and Prevention 1 Lee S. Cohen, M.D.
  • 2.
    Risk of PsychiatricIllness During Pregnancy and Postpartum Period 2 Kendell et al. Br J Psychiatry. 1987;150:662 Admissions Per Month 60 50 40 30 20 10 -2 Years -1 Year Childbirth +1 Year +2 Years Pregnancy
  • 3.
    Spectrum of PostpartumMood Disorders 3 Postpartum Psychosis Postpartum Symptom Severity Postpartum Depression (10-15%) None Postpartum Blues (50-85%)
  • 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 4
  • 5.
    Postpartum Depression • Majorand minor depression occurs in approximately 10% of women after live childbirth; range 5% to 15%1-4 • 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 5 1. O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171. 2. O’Hara MW, et al. J Abnorm Psychol. 1991;100:63-73. 3. Kumar R, Robson RM. Br J Psychiatry. 1984;144:35-47. 4. Kendall K, et al. Br J Psychiatry. 1987;150:662-673. 5. 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 asa 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 6
  • 7.
    Psychiatric History PredictsRisk of Depression in the Postpartum Period 7 1. O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171. 2. O’Hara MW, et al. Postpartum Depression: Causes and Consequences. New York, NY: Springer-Verlag; 1995. 0 10 20 30 40 50 60 Risk in general population 1 History of major depression 2 History of postpartum depression 2 Incidence (%)
  • 8.
    Postpartum Anxiety Disorders •Postpartum panic disorder • Postpartum OCD : can be seen in the absence of PPD • Comorbid depression and anxiety commo 8
  • 9.
    PPD: Obsessions andCompulsions • Intrusive obsessional thoughts common • Thoughts of doing harm to infant • Obsessions more common in PPD (57%) than in non- puerperal MDD (36%) 9 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 10
  • 11.
    What is therelationship between PPD and Bipolar Disorder ? 11
  • 12.
    Bipolarity in PostpartumDepression • 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 12 Ghaemi et al, 2002
  • 13.
    High Risk forPostpartum 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%) 13 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: FurtherEvidence 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 14 Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917. Coyle N, et al. Lancet. 2000;356:1490-1491.
  • 15.
    Longitudinal Course ofPostpartum Psychosis • 95 % affective psychosis (bipolar disorder or schizoaffective disorder) • 5 % schizophrenia • Recurrence of affective episodes is the rule though circumscribed illness may be seen 15 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 16
  • 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 17
  • 18.
    Edinburgh Postnatal DepressionScale (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 18 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? 19 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 PredictorsInventory 20 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.
  • 22.
  • 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 23 Bloch 2000
  • 24.
  • 25.
    Treatment of Depressionin the Postpartum Period: Psychotherapy 25 1. O'Hara MW, et al. Arch Gen Psych. 2000;57:1039-1045. 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. Treatment n Design Results IPT1,2 120 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 IPT=interpersonal psychotherapy; CBT=cognitive behavioral therapy;  =decrease; RCT=randomized, controlled trial.
  • 26.
    Postpartum Depression: PharmacologicTreatment Fluoxetine Appleby, 1997 Double-Blind Paroxetine Misri, 2004 Double-Blind Sertraline Wisner, 2006 Double-Blind Nortriptyline Wisner, 2006 Double-Blind Sertraline Stowe, 1995 Open Fluvoxamine Suri, 2002 Open Venlafaxine Cohen, 2001 Open Bupropion Nonacs, 2004 Open 26
  • 27.
    Venlafaxine for PPD:Treatment Response 27 Cohen LS et al, 2001. J Clin Psychiatry 62:592-596. Ham-D * = p<.0001 ** = p<.0001 0 Kellner Anxiety * = p<.0001 ** = p<.0001 1 2 3 4 5 0 CGI * = p<.0001 ** = p<.0001 5 10 15 20 25 0 Base End Week 4 ** * Base End Week 4 Base End Week 4 ** * ** * 5 10 15 20 25
  • 28.
    Postpartum Depression: Comparing TreatmentResponse • Most studies on serotonergic agents • SSRIs and TCAs have similar efficacy • Bupropion may be less effective 28 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. 0 20 40 60 80 100 SERT OPEN VEN OPEN BUP OPEN Response Remission % of Patients
  • 29.
    Postpartum Depression: PharmacologicStrategies • 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) 29
  • 30.
    Treatment of BipolarDepression 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 30
  • 31.
    Postpartum Depression: Isthere a Role for Hormonal Treatment ? • Progesterone: Inconsistent findings • Progesterone may exacerbate mood symptoms ? • Estrogen: Beneficial alone or as adjunct to antidepressant 31 Gregoire 1996, Ahokas 2001
  • 32.
    Estrogen for PostpartumDepression • 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 32 Gregoire, 1996
  • 33.
    Estrogen for PostpartumDepression • 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) 33 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 34
  • 35.
  • 36.
    Psychotropic Medications andBreast-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 36
  • 37.
    Which Antidepressant isthe 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 37
  • 38.
  • 39.
    39 Identification of womenat high risk for postpartum psychiatric illness Is this disorder preventable?
  • 40.
    Stratification of Risk 40 Nohistory Routine Hx of MDD Consider Prophylaxis Hx of PPD OR Antidepressant Recurrent Severe MDD Prophylaxis Hx of Bipolar Disorder OR Intense Monitoring AND PP Psychosis Li Prophylaxis LOW HIGH
  • 41.
    Risk of RelapseFollowing Lithium Discontinuation 41 Viguera AC. Am J Psychiatry. 2000;157:179-184. 40 44 48 52 56 60 64 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 Weeks at Risk Off Lithium % Remaining Stable Pregnancy (Weeks 1–40) Postpartum (Weeks 41–64) Nonpregnant Postpartum Nonpregnant Pregnant (n=42) (n=59) (n=20) (n=25)
  • 42.
    Non-Pharmacologic Prophylaxis • Positiveeffect of IPT during pregnancy – 13 women with depression during pregnancy – IPT induced remission in all – No women developed PP 42 Spinelli 1997
  • 43.
    Pharmacologic Prophylaxis: Postpartum MajorDepression • 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) 43
  • 44.
    Depression in WomenTreated 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 44 Wisner KL et al, 2004. Am J Psychiatry 161:1290-1292.
  • 45.
    Postpartum Prophylaxis forWomen with Bipolar Disorder 45
  • 46.
    Postpartum Lithium Prophylaxis forBipolar Women 46 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 withMood Stabilizers other than lithium 47 Wisner KL et al Biol Psychiatry 2004;56:592-596; Sharma V et al. Bipolar Disord 2006;8:400-4 Subjects (Dx) Benefit Wisner, 2004 Valproate +/- Bipolar disorder Sharma , 2006 olanzapine + Puerperal psychosis/Bipolar disorder
  • 48.
    Postpartum Prophylaxis inBipolar Women 48 Cohen LS, Sichel DA, et al. Am J Psychiatry. 1995. Significant difference between groups (Peto-Peto-Wilcoxen 2=6.966, df=1,p<0.01) Cumulative Survival Time (Weeks) Prophylaxis (N=14) No Prophylaxis (N=13)
  • 49.
  • 50.
    Impact of MaternalDepression 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 50 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 PostpartumDepression (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 51 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 Effectson 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) 52 Hay DF et al. J Child Psychol Psychiatry. 2001;42:871-889.
  • 53.
    Summary • Postpartum psychiatricillness 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 53
  • 54.