This document summarizes a study on preventing postpartum psychosis and mania in women at high risk. The study evaluated 618 referrals to a peripartum prevention program. It found that lithium prophylaxis initiated immediately postpartum completely prevented relapse in high-risk women with a history of postpartum psychosis only. In contrast, women with bipolar disorder had substantial risk of relapse during pregnancy and postpartum without continuous prophylaxis throughout this period. The authors recommend prophylactic treatment immediately postpartum for women with a history of postpartum psychosis only, and continuous prophylaxis throughout pregnancy and postpartum for women with bipolar disorder.

1. A B D U L M A N N A N C H A T T H A M 0 9 0 2 1
C L A S S O F 2 0 1 4
JOURNAL CLUB
PRESENTATION

2. V E E R L E B E R G I N K , M . D . ; P A U L F . B O U V Y , M . D . , P H . D . ;
J E R O E N S . P . V E R V O O R T , N . P . ; K A T H E L I J N E M .
K O O R E N G E V E L , M . D . , P H . D . ; E R I C A . P . S T E E G E R S , M . D . ,
P H . D . ; S T E V E N A . K U S H N E R , M . D . , P H . D .
A M J P S Y C H I A T R Y 2 0 1 2 ; 1 6 9 : 6 0 9 -
6 1 5 . 1 0 . 1 1 7 6 / A P P I . A J P . 2 0 1 2 . 1 1 0 7 1 0 4 7
Prevention of Postpartum
Psychosis and Mania in women at
high risk

3. TABLE OF CONTENTS
 BACKGROUND
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS

4. BACKGROUND
 Psychotic episodes during the postpartum period are life-
threatening psychiatric emergencies, occurring after
nearly 0.1% of all deliveries.
 The strongest predictor for postpartum psychosis is a
history of bipolar disorder and/or postpartum psychosis
 previous studies in high-risk women provide strong
support for the benefits of lithium prophylaxis during
pregnancy and the postpartum period

5.  Viguera et al. provided clear evidence that discontinuation of
medication leads to high rates of relapse in bipolar women during
pregnancy.
 four studies with smaller study groups have shown that prophylaxis
with lithium is protective for the occurrence of relapse postpartum.
 In all four studies, lithium was continued during pregnancy, started in
the last trimester of pregnancy, or started immediately postpartum.
 While lithium has been demonstrated to be effective in substantially
reducing the risk of peripartum relapse, the precise timing of when to
initiate lithium prophylaxis, during pregnancy or immediately
postpartum, remains unclear
Viguera AC; Whitfield T; Baldessarini RJ; Newport DJ; Stowe Z; Reminick A; Zurick A; Cohen LS: Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood
stabilizer discontinuation. Am J Psychiatry 2007; 164:1817–1824
van Gent EM; Verhoeven WM: Bipolar illness, lithium prophylaxis, and pregnancy. Pharmacopsychiatry 1992; 25:187–191

6.  It is important to note that although postpartum psychosis
is widely considered as a new episode of bipolar disorder,
some studies have indicated that postpartum psychosis is
distinct from bipolar disorder.
 “postpartum psychosis” is defined as a history of any of the
following DSM-IV diagnoses: psychotic disorder not
otherwise specified, brief psychotic disorder, or mood
disorder (manic, mixed, or major depressive episode) with
psychotic features, all requiring the specifier “with
postpartum onset” (≤4 weeks after delivery)
Platz C; Kendell RE: A matched-control follow-up and family study of 'puerperal psychoses.' Br J Psychiatry 1988; 153:90–94
Winokur G: Postpartum mania. Br J Psychiatry 1988; 153:843–844

7. METHODS
 Between January 2003 and December 2010, a total
of 618 referrals to the outpatient clinic of the
Peripartum Prevention Program at the Department
of Psychiatry, Erasmus Medical Center (Rotterdam,
the Netherlands), were evaluated.
 Requests for evaluation and clinical management
during pregnancy and the postpartum period were
made by obstetricians, psychiatrists, and general
practitioners.

8. INCLUSION CRITERIA
 women with bipolar I or bipolar II disorder with only
nonpuerperal episodes and those with both
puerperal and nonpuerperal episodes.
 All of these women had at least one previous
delivery.
 women with a history of postpartum psychosis but
without any manic or psychotic symptoms outside
the postpartum period.

9. EXCLUSION CRITERIA
 Women with chronic psychotic disorders such as
schizophrenia or schizoaffective disorder.

11. Peripartum Prevention Program
 The Peripartum Prevention Program was designed to
provide standardized evidence-based clinical care for
women at high risk for peripartum relapse.
 Women enrolled in the program received their full
obstetric care through the Department of Obstetrics and
Gynecology and peripartum psychiatric care through the
Department of Psychiatry .
 Women already taking maintenance lithium were
prescribed doses three times a day during pregnancy to
avoid peak lithium levels. After delivery dosage was
reduced to one per day.

12.  Women who were initially medication free were
advised to start lithium prophylaxis immediately
postpartum.
 lithium was started the first evening after delivery
and given once daily according to the plasma level
(target minimum, 0.8 mmol/L).
 Plasma lithium levels were monitored twice weekly
during the first week postpartum, once per week
during weeks 2 and 3, and thereafter as clinically
indicated.

13.  All women were advised to spend the first week
postpartum in a private room on the inpatient
obstetric ward, where nurses performed the
overnight newborn feedings to provide mothers with
the opportunity to sleep throughout the night.
Lorazepam 1mg at bedtime was the recommended
standardized treatment.
 All women received follow-up evaluations every 4–6
weeks throughout the peripartum period.
 The mean period of follow-up was 12.6 weeks
postpartum (range=4–52 weeks).

14. Statistical Analysis
 SAS, version 9 (SAS Institute, Cary, N.C.)
 categorical data was evaluated by means of Fisher's
exact test.
 continuous variables were examined with two-
sample t tests.
 All hypotheses were tested with an alpha of 0.05
(two-sided).

15. RESULTS
• The timing of relapse was substantially different between
the women with bipolar disorder and those with
postpartum psychosis only.

16.  Remarkably, despite being medication free
throughout the entire pregnancy, none of the 29
women with postpartum psychosis relapsed during
pregnancy. Postpartum, four of the 29 (13.8%)
relapsed.
 Of these four women with previous postpartum
psychosis, the current relapse was manifested as
mania for one woman, psychosis for one, a mixed
episode for one, and depression for one.
 Three of these four women required postpartum
inpatient admission.

17.  In contrast to the women with a history of
postpartum psychosis only, none of whom had a
relapse during pregnancy, 24.4% of the women with
bipolar disorder (10 of 41) relapsed during
pregnancy (p<0.01, Fisher's exact test).
 Of these 10 women, five had a manic episode, two
had a mixed episode, two had a major depressive
episode, and one developed hypomania
 Those with a manic or mixed episode all required
hospitalization.

19. • Relapse postpartum occurred in 22.0% of the women
with bipolar disorder (nine of 41), the majority of
whom (six of nine) had also previously relapsed
during pregnancy.
 Three out of these six women achieved full
remission after the relapse during pregnancy but
relapsed again postpartum.
 Consequently, relapse during pregnancy was a
significant risk factor for relapse postpartum
(p<0.01, Fisher's exact test; odds ratio=14.0, 95%
CI=2.5–80.0).

20.  Of all nine women with bipolar disorder and
postpartum relapse, three had a manic episode, one
had a mixed episode, three had depression, and two
had hypomania.

21. Influence of Prophylactic Medication in
Women With Postpartum Psychosis Only
 Of the 29 patients with a history of postpartum psychosis
only, 20 began prophylactic treatment within 24 hours of
delivery. Of these 20, 17 used lithium and three used
antipsychotics.
 Notably, there were no cases of relapse among the women
with postpartum psychosis who initiated postpartum
prophylaxis upon delivery.
 The relapse rate in the women without postpartum
prophylaxis and a history of postpartum psychosis was
44.4% (four of nine).
 The difference in relapse rates between the patients with
and without prophylaxis was significant (p<0.01, Fisher's
exact test).

22. Influence of Prophylactic Medication in
Women With Bipolar Disorder
 Of the 41 women with bipolar disorder, 31 (75.6%)
received maintenance prophylaxis during pregnancy
 Ten (24.4%) of the 41 bipolar women did not use
prophylaxis continuously throughout pregnancy.
 The relapse rate during the pregnancies of the women
with bipolar disorder who used prophylaxis was 19.4%
(six of 31), compared to 40.0% (four of 10) in women
without prophylaxis.
 However, despite maintenance mood stabilization,
60.0% (six of 10) of the women who relapsed during
pregnancy also experienced a postpartum relapse
(p<0.01, Fisher's exact test; odds ratio=14.0, 95%
CI=2.5–80.0).

24. DISCUSSION
 Designed a peripartum prevention program using
the best available evidence for pregnant women with
the two strongest risk factors for postpartum
psychosis: a previous postpartum psychosis and/or a
history of bipolar disorder.
 Confirmed that lithium is highly efficacious for
peripartum prophylaxis.
 Findings suggest that postpartum prophylaxis is
highly efficacious in women at high risk for
postpartum psychosis who do not have a diagnosis of
bipolar disorder

25.  findings support a wide literature demonstrating
that women with bipolar disorder have a substantial
risk of relapse during pregnancy as well as in the
postpartum period
 In contrast, women with a history of only
postpartum psychosis have a vulnerability for mania
or psychosis that is restricted to the postpartum
period.
 data contribute to the emerging consensus that
women with a history of psychosis limited to the
postpartum period might have a distinct variant of
bipolar disorder

26. Limitations
 Missed symptoms associated with transient
instability as the study was principally designed to
detect mood episodes fulfilling DSM-IV criteria.
 Study was naturalistic, leaving open the possibility
that some of the outcomes were influenced by
patients' preferences

27. Strengths
 primary pharmacologic treatment recommendation
for high-risk women was lithium, based on the
literature.
 In contrast, studies using other prophylactic
postpartum treatment strategies in bipolar women
either failed to show efficacy, as in the case of
estrogen administration and valproate, or were
inconclusive, as in the case of olanzapine.

28. CONCLUSIONS
 The authors recommend initiating prophylactic
treatment immediately postpartum in women with a
history of psychosis limited to the postpartum
period, to avoid in utero fetal exposure to
medication.
 Patients with bipolar disorder require continuous
prophylaxis throughout pregnancy and the
postpartum period to reduce peripartum relapse risk.

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