REVIEW ARTICLE

Interventions for the prevention and treatmentof postpartum psychosis: a systematic review

Shelley Doucet & Ian Jones & Nicole Letourneau &

Cindy-Lee Dennis & Emma Robertson Blackmore

Received: 29 March 2010 /Accepted: 10 November 2010 /Published online: 3 December 2010# Springer-Verlag 2010

Abstract Postpartum psychosis is a serious disorder that cancause negative consequences for the mother, infant, and entirefamily. While reports of this condition date back for centuries,little is known about what interventions are most effective forthis population. The purpose of this systematic review was toexamine the research evidence on interventions for theprevention and treatment of postpartum psychosis. Studieswere searched using CINAHL, EMBASE, MEDLINE,PsycINFO, and PubMed databases. All primary researchstudies published in English since 1970 that exploredinterventions for the prevention or treatment of postpartum

psychosis were included. The search resulted in 26 studies oninterventions for postpartum psychosis, with 10 focusing onprevention and 17 focusing on treatment. Studies on theprevention of postpartum psychosis have examined the effectsof mood stabilizers, antipsychotics, and hormone therapy,while those examining treatment have included electrocon-vulsive therapy, mood stabilizers, antipsychotics, hormones,and the beta blocker propranolol. Only preliminary evidencesuggests which interventions may be effective strategies toprevent (e.g., lithium) and treat (e.g., electroconvulsivetherapy) postpartum psychosis. Due to methodological limi-tations in the studies reviewed, extensive evidence-basedrecommendations for the prevention and treatment of post-partum psychosis cannot be made. The known risk factors andnegative consequences of postpartum psychosis point to theimportance of preventative and acute treatment measures.Well-designed prospective studies are needed to determine theefficacy of prevention and treatment interventions for womenwho experience postpartum psychosis.

Keywords Postpartum psychosis . Prevention . Treatment .

Systematic review

Postpartum psychosis (PP) is a psychiatric emergency thatrequires immediate medical attention. Despite the experienceof PP dating back centuries (Brockington 1996), little isknown about what interventions are most effective for thisvulnerable population. Research on interventions for womenwho experience PP has been limited due to barriers such asthe relative rarity of this disorder and exclusion from drugtrials for safety concerns. Affecting one to two per 1,000deliveries (Kendell et al. 1987), PP can cause severalnegative consequences, including impaired mother–infantbonding (Hipwell et al. 2000), infant abuse and neglect(Chandra et al. 2006), the risk of recurrent psychiatric illness

S. Doucet (*)Department of Nursing and Health Sciences,University of New Brunswick,100 Tucker Park Road, P.O. Box 5050, Saint John, NB E2L 4L5,Canadae-mail: sdoucet@unb.ca

I. JonesMRC Center for Neuropsychiatric Genetics and Genomics,Department of Psychological Medicine and Neurology,Cardiff University,The Henry Wellcome Building for Biomedical Research in Wales,Academic Avenue, Heath Park,Cardiff CF14 4XN, UK

N. LetourneauFaculty of Nursing, University of New Brunswick,PO Box 4400, Fredericton, NB E3B 5A3, Canada

C.-L. DennisFaculties of Nursing and Medicine, Department of Psychiatry,University of Toronto,155 College Street, Rm. 280,Toronto, ON M5T 1P8, Canada

E. R. BlackmoreDepartment of Psychiatry,University of Rochester Medical Center,BOX PSYCH 4-9200, 300 Crittenden Boulevard,Rochester, NY 14642-8409, USA

Arch Womens Ment Health (2011) 14:89–98DOI 10.1007/s00737-010-0199-6

(Robertson et al. 2005; Terp et al. 1999), suicide (Appleby etal. 1998), and infanticide (Spinelli 2004). PP is at timesconfused or used interchangeably with postpartum depression.Postpartum depression refers to a non-psychotic depressiveepisode that often requires treatment and affects approximately13% of mothers within 12 weeks of giving birth (O’Hara andSwain 1996). PP is more severe than postpartum depression,often requiring hospitalization, and is characterized bydelusions, hallucinations, bizarre behavior, depression, mania,and mood lability that usually presents within the first 2 weekspostpartum (Heron et al. 2008; Sit et al. 2006).

Another barrier to conducting research related to PP is thatthe nosology of this disorder remains disputed. The evidencesuggests, however, that PP is usually mania or affectivepsychosis linked temporally with childbirth (Brockington1996). The Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition (DSM-IV; American PsychiatricAssociation 2000), and the International Classification ofDiseases, Tenth Revision (ICD-10;World Health Organization1992) do not recognize PP as a distinct condition; rather, PPis diagnosed within various non-postpartum psychiatricdisorders if the onset occurs within 4 and 6 weeks postpar-tum, respectively. The differential diagnosis for PP episodescan include major depression with psychotic features, bipolarI, bipolar II, schizoaffective, unspecified functional psychosis,and brief psychotic disorder. Studies suggest that PP is often amanifestation of a bipolar disorder condition that is triggeredby childbirth (Brockington et al. 1981; Jones and Craddock2001; Kendell et al. 1987). Approximately 25–50% ofwomen who give birth and have a history of bipolar disorderexperience an episode of PP (Brockington 1996; Jones andCraddock 2001), while rates as high as 74% have beenreported with women who also have a family history of PP(Jones and Craddock 2001). Recent epidemiological researchsuggests that in primiparous women, the relative risk forhospital admission with bipolar disorder during the firstmonth postpartum is 23 (Munk-Olsen et al. 2006). Thisfinding is four times higher than the relative risk for hospitaladmission with schizophrenia. Further support for theincreased risk of bipolar disorder recurrence postnatallycomes from research demonstrating high relapse rates amongwomen who discontinue their lithium (Viguera et al. 2000).In a retrospective study, Viguera et al. (2000) found that 70%of women who stopped their lithium treatment duringpregnancy experienced a recurrence of their bipolar disorderin the postpartum period, compared to 24% of non-pregnantmatched women. A personal history of PP also predisposesapproximately 57% of women to experience another episodeafter a subsequent pregnancy (Robertson et al. 2005).

Considering it is well documented that a history ofbipolar disorder or PP are significant risk factors for arelapse postnatally, preventative strategies are warranted.Given the seriousness of PP, gaining a better understanding

of effective treatment interventions is also critical in orderto address the immediate effects and decrease the long-termhealth consequences.

Aim

While there are general guidelines available on the treatmentof bipolar disorder or affective psychosis (e.g., AmericanPsychiatric Association http://www.psychiatryonline.com/pracGuide/pracGuideTopic_8.aspx), specific guidelines onthe prevention and treatment of PP for perinatal healthprofessionals are primarily limited to the UK (e.g., NICE,SIGN, and CEMACH). In light of the seriousness of PP, agreater understanding of effective interventions is essential toimprove outcomes for this vulnerable population. Thepurpose of this systematic review was to examine theevidence on interventions for the prevention and treatmentof PP. It is beyond the scope of this review to evaluate theevidence of reproductive safety for medications used inpregnancy or breastfeeding; a review examining this specificarea has already been previously published (Stowe 2007).

Methods

Search methods

Databases systematically searched for this review includedCINAHL (1982–2009), EMBASE (1980–2009), MEDLINE(1950–2009), PsycINFO (1806–2009), and PubMed (1966–2009). Due to the dearth of research on PP, and to ensure thatno studies were missed, all studies including the key searchterms postpartum psychosis, puerperal psychosis, or postnatalpsychosis were reviewed for inclusion. Additional literaturewas located through reviewing the citations of the retrievedstudies and by contacting subject experts.

Inclusion and exclusion criteria

All primary research studies published in English andsince 1970 that explored the effectiveness of interven-tions for the prevention or treatment of PP were includedin this review. For the prevention studies, the interven-tion must have begun prior to the presentation of manicor affective psychotic symptoms either during pregnancyor immediately postpartum. For the treatment studies, theonset of mania or affective psychosis had to haveoccurred within the first year postpartum. As previouslystated, although symptoms generally develop within2 weeks of delivery, research studies can identifysubjects with PP using two different strategies. Someauthors use specific diagnostic criteria ascertained

90 S. Doucet et al.

through medical records while others use temporalcriteria that links symptoms to childbirth. As such, weused the criterion of onset of mania or affectivepsychosis within 1 year of parturition to ensure thatkey studies were not omitted. Studies based solely onbaby blues or postpartum depression were excluded;however, studies that included mixed samples includingboth women who experienced postpartum depression andPP were included to ensure that research on preventionand treatment strategies for PP was thoroughly reviewed.

Quality appraisal, data abstraction, and synthesis

Due to the limited number of studies on interventions forPP, all research designs were included. Studies, caseseries, or case reports of very poor methodological qualitywere excluded when we could not establish the preventionor treatment intervention used. Data were extracted usingan abstraction form and details related to disorderdefinition (i.e., diagnostic/screening criteria used), popu-lation sampled (i.e., participant characteristics, samplesize, recruitment process, inclusion/exclusion criteria),study design (i.e., method and timing of assessment,outcome measures, length of follow-up), intervention,and results were collected. Interventions were categorizedas prevention or treatment, and were subcategorizedaccording to the specific interventional approach used.

Results

The first author reviewed the titles of approximately 800papers. After scanning the titles for inclusion, approxi-mately 270 abstracts were specifically examined accord-ing to the inclusion criteria. The search resulted in 26intervention studies (one study included both preventionand treatment interventions). Table 1 summarizes theresults of 10 studies that explored the prevention of PP.Table 2 summarizes the results of 17 studies that exploredthe treatment of PP. All studies that met the inclusioncriteria for this review were those that examined biologicalinterventions such as pharmacotherapy and electroconvulsivetherapy.

Prevention of PP

Research on the prevention of PP has focused on the effectsof mood stabilizers, antipsychotics, and hormone therapy.The sample size for the 10 prevention studies ranged from 1to 29, while over half (60%) of the studies had between 17and 29 participants. Half (50%) of the studies were smallclinical trials, while the remainder were primarily casestudies or retrospective reports.

Mood stabilizers Six studies evaluated the effects of moodstabilizers for the prevention of PP. In an open clinical trialconducted in Canada, the Netherlands, and the UK, 21women who met the Research Diagnostic Criteria (RDC)for history of PP were administered lithium at 34 weeksgestation or within 24 h of delivery (Stewart et al. 1991). At6 months postpartum, only two (10%) women hadexperienced an episode of PP. In an earlier case study byStewart (1988) in Canada, four women who had a history ofPP were administered prophylactic lithium immediatelyfollowing delivery and there were no reported relapses of PP.

UK researchers evaluated the effectiveness of lithiumprophylaxis in a retrospective study including 17 womenwho met the RDC criteria for bipolar disorder or history ofpuerperal affective psychosis (Austin 1992). Within3 months postpartum, only two (22%) of the nine womenwho received prophylactic lithium relapsed in comparisonto six (75%) of the eight women who did not receiveprophylactic lithium. It should be noted that three of thewomen in the treatment group were also included in thestudy of Stewart et al. (1991). In another retrospective studyincluding US women who met the DSM-III-R criteria forbipolar disorder, 14 of the 27 women received variouscombinations of prophylactic mood stabilizers (Cohen et al.1995). All but one woman received lithium alone or incombination with either carbamazepine or an antidepres-sant. Only one (7%) of the 14 in the treatment grouprelapsed, in comparison to eight (62%) of the 13 in the non-treatment group at 3 months postpartum. The relative riskof relapse was 8.6 times greater for women who did notreceive prophylactic mood stabilizers.

Support for the prophylactic effect of lithium also comesfrom a prospective study of 11 women from the Nether-lands who met DSM-III criteria for bipolar disorder (vanGent and Verhoeven 1992). Five of the women werestudied during two pregnancies. Of the 16 pregnancies,eight women received prophylactic lithium, two receivedprophylactic carbamazepine, one received prophylactichaloperidol, while five received no medications. Within3 months postpartum, three (27%) of the 11 women whowere treated with either lithium, carbamazepine, or halo-peridol experienced a manic or psychotic relapse comparedto three (60%) of five women who refused treatment.

The effects of the mood stabilizer divalproex inpreventing postpartum relapse were evaluated in an openclinical trial including 26 US women with a DSM-IVdiagnosis of bipolar disorder (Wisner et al. 2004). Fifteenof the women received divalproex immediately postpartum,while 11 of the women received only symptom monitoring.Participants were assessed weekly for 20 weeks using theStructured Clinical Interview for DSM-IV, the HamiltonRating Scale for Depression, the Bech–Rafaelson ManiaScale, the Mania Rating Scale, the Global Assessment of

Prevention and treatment of postpartum psychosis 91

Tab

le1

Postpartum

psycho

sispreventiv

einterventio

nstud

ies

Study

Design

Participants

Interventio

nsResults

Notes

Austin

1992

Retrospectiv

estudy

17UK

wom

enwho

met

theRDC

criteriaforbipolardisorder

orpuerperaleffectivepsychosis

Liprophylaxis(serum

levelsof

0.4mmol/1

ormore)

during

pregnancy(7/9)or

with

in48

hfollo

wingdeliv

ery(2/9)

2/9(22%

)in

thetreatm

entgrouprelapsed,

comparedto

6/8(75%

)in

thenon-

treatm

entgroupat

3monthspostpartum

Three

inthetreatm

entgroup

werealso

included

inthe

studyby

Stewartet

al.(1991)

Cohen

etal.1995

Retrospectiv

estudy

27USwom

enwho

met

DSM-III-R

criteriaforbipolardisorder

4/27

also

hadahistoryof

PP

Various

prophylactic

moodstabilizers

Li

alone=

9LiandCBZ=2Liandan

antid

epressant=

2CBZ=1

1/14

(7%)of

thetreatm

entgrouprelapsed,

comparedto

8/13

(62%

)in

thenon-

treatm

entgroupat

3monthspostpartum

Doses

werenotspecified

Kum

aret

al.2003

Openclinical

trial

29UK

wom

enwith

aRDCdiagnosis

ofhypomania,mania,or

schizoaffectivedisorder

Prophylactic

transdermal

17ß-estradiolwith

in48

hof

birthin

dosesof

200,

400,

or800μg/day,

reducedover

12days

12/29(41%

)relapsed,of

which,thosewho

received

thedose

of800μg/dayrequired

less

subsequent

psychotropic

medication

andrecoveredsooner

Onset

ofrelapsewas

with

in14

days

postpartum

for10

wom

en,and75

and77

days

for2wom

en

Murray1990

Casestudy

One

UK

wom

anwith

ahistoryof

PP

Duringsecond

pregnancyprophylactic

progesterone

400mg/dwas

administered

andincreasedto

800mg/dafterdeliv

ery.

After

3rd

pregnancy,

thioridazine

prophylaxis50

mgtid

Prophylactic

progesterone

didnotprevent

relapseof

PPthat

occurred

9days

postpartum

.Prophylactic

thioridazine

didpreventrelapseafter3rd

pregnancy

Study

isalso

included

underthe

treatm

entof

PP.

Thiorida-zine

was

takenoffmarketbecause

ofadverseeffects

Sharm

aet

al.2006

Openclinical

trial

25Canadianwom

enwith

ahistory

ofbipolardisorder

Prophylactic

olanzapine

alone(5–1

0mg)

orin

combinatio

nwith

anantid

epressantor

moodstabilizer=

11.Antidepressants,

moodstabilizers,or

nomedication=14

2/11

(18%

)wom

enin

theolanzapine

group

relapsed,in

comparisonto

8/14

(57%

)of

thewom

enin

theno

olanzapine

group

with

in4weekpostpartum

Sichelet

al.1995

Openclinical

trial

11USwom

enwho

met

DSM-III-R

criteriaforhistoryof

PP(n=7)

orPPD

(n=4).Noneexperienced

non-postpartum

affectiveillness

Prophylactic

oral

estrogen

(5mg,

bid)

immediately

afterdeliv

ery(dosereduced

over

4week).2/11

also

received

IVestrogen

toensure

compliancefor2days

1/11

(9%)relapsed

attheone-year

follo

w-up

Onset

ofrelapsewas

1weekpostpartum

All10

who

compliedwith

treatm

entdidnotrelapseNo

indicatio

nof

whether

the

relapsewas

PPD

orPP

Stewart1988

Caseseries

FourCanadianwom

enwith

historyof

PP,

3/4diagnosedwith

bipolardisorder

Prophylactic

Li(900–1

,200

mg/d)

immediately

follo

wingdeliv

ery

Lipreventedrelapsein

all4cases,maintained

at6month

follo

w-up

Stewartet

al.1991

Openclinical

trial

21wom

enfrom

Canada,

theNetherlands,

ortheUK

with

ahistoryof

PP

accordingto

theRDC

Prophylactic

Li(750–1

,200

mg/d)

at34-w

eek

gestation(5/21)

orwith

in24

hafterdeliv

ery

(16/21)

2/21

(10%

)relapsed

with

in8days

postpartum

,both

mild

Nootherrelapseat

6months

One

motherwho

beganLi

before

deliv

erysuffered

astillbirth

vanGentand

Verhoeven

1992

Prospectiv

ethree-center

study

Elevenwom

enfrom

theNetherlands

who

met

DSM-IIIcriteriaforbipolar

disorder,5becamepregnant

twice

Prophylactic

Li(serum

levelsup

to0.7mmol/1)=

8CBZ=2Haloperidol=1Refused

treatm

ent

group=5

3/11

(27%

)of

thetreatm

entgroup

experiencedmanic/psychotic

relapsewith

in3months,

comparedto

3/5(60%

)who

refusedtreatm

ent

The

prophy-lactic

effectsof

Li,

CBZ,andhaloperidolwere

notspecified

Wisneret

al.2004

Openclinical

trial

26USwom

enwith

aDSM-IV

diagnosisof

bipolardisorder

Divalproex(250

mg/bidas

tolerated)

and

symptom

monito

ring

immediately

postpartum

=15

Postpartum

symptom

monito

ring

alone=

11

10/15(67%

)of

thewom

enwho

received

divalproex

and8/11

(73%

)of

thewom

enwho

wereunmedicated

relapsed

with

in20

weekpostpartum

.Nosignificantdifferencesbetweengroups

RDC

ResearchDiagn

ostic

Criteria,

DSM

Diagn

ostic

andStatistical

Manualof

MentalDisorders,PPpo

stpartum

psycho

sis,PPD

postpartum

depression

,Lilithium

,CBZcarbam

azepine

92 S. Doucet et al.

Tab

le2

Postpartum

psycho

sistreatm

entinterventio

nstud

ies

Study

Design

Participants

Interventio

nsResults

Notes

Ahokasand

Aito

1999

Caseseries

Twowom

enfrom

Finland

with

onsetof

PP

1–4weeks

postpartum

Bothcasestreatedwith

sublingual

17ß-estradiol

(4–6

mg/day)

1case

was

first

treatedwith

CPZ200mg/dfor2weeks

CPZhadlittle

effect

Psychotic

symptom

sdecreased

with

in1weekon

estradiolas

measuredby

theBPRS,

andboth

madeacompleterecovery.Bothwom

anstoppedtreatm

entandrelapsed

with

in2weeks

Ahokaset

al.2000a

Open-labeltrial

Tenwom

enfrom

Finland

meetin

gtheICD-10

criteriaforpsychosiswith

postpartum

onset,

(meanonset=12.3

days,SD=8.3)

All11

received

sublingual

17ß-estradiol

(3–6

mg/d)

2wom

enfirsttreatedwith

CPZ300–

400mg/dforup

to3week.

Twowom

enfirsttreated

with

haloperidol8–20

mg/dforup

to17

days

CPZandhaloperidolhadlittle

effect

Psychotic

symptom

sdecreasedwith

in1weekon

estradiolas

measuredby

theBPRS.1wom

anwho

stoppedtreatm

entrelapsed

with

in1week

Twowom

enalso

received

psycho-therapy

before

estradiolwith

little

effect

Ahokaset

al.2000b

Caseseries

Twowom

enfrom

Finland

with

onset

ofPP1–2weeks

postpartum

Bothcasestreatedwith

sublingual

17ß-estradiol

(3–4

mg/d)

1case

was

firsttreatedwith

haloperidol

upto

20mg/dfor17

days

Haloperidol

hadlittle

effect

Psychotic

symptom

sdecreasedwith

in10

days

onestradiolas

measured

byBPRS1wom

anwho

stoppedtreatm

entrelapsed

with

in1week

Atkinsonand

Atkinson1983

Casestudy

One

UK

wom

anwith

onsetof

PP

with

in7weeks

postpartum

Progesterone(injectio

nsandsupposito

ries)

Hallucinatio

nsanddelusionsdecreasedwith

in1month,

afternotresponding

toatranquilizer

Writtenby

affected

mother

andhusbandDosenot

specified

Forrayand

Ostroff2007

Caseseries

FiveUSwom

enwith

severe

treatm

ent

refractory

PPandPPD

Onset

3weeks—11

monthspostpartum

ECT3tim

esaweek

All5wom

enim

proved

with

in3–6sessions

whenprior

pharmacotherapy

was

unsuccessful

Huang

etal.2008

Casestudy

One

wom

anfrom

Taiwan

with

ahistoryof

mania

Onset

ofPP

1month

postpartum

Lialoneor

variouslycombinedwith

CBZ,valproic

acid,andhaloperidol.HRTwith

conjugated

estrogen

0.625mg/dandmedroxy-progesterone2.5mg/day

Poortreatm

entresponse

with

alltreatm

ents,except

forHRT,

which

was

effectivewith

in2weeks

Iruela

etal.1992

Casestudy

One

wom

anfrom

Spain

with

onsetof

psychosis3days

postpartum

Antidepressantsandanxiolytics.Haloperidol

(4mg/day)

andmethotrim

eprazine

(75mg/day).

Pim

ozide(8

mg/day)

Pim

ozidewas

effectivewith

in4days

andremained

asym

ptom

atic

at3year.Allothertreatm

entswere

ineffective

Antide-pressant

andanx-

iolytic

drugsnotspecified

Kornhuber

and

Weller1991

Casestudy

One

wom

enfrom

Germanywith

onset

ofpsychosis1weekpostpartum

Zuclopenthixoldecanoate600mgClozapine

200mg

Zuclopenthixoldecanoatecaused

severe

extrapyram

idal

side

effects.Clozapine

was

substituted

andwas

effectivewith

in1week

Lichtenberg

etal.1988

Casestudy

One

wom

anfrom

Israel

with

onsetof

psychosis3days

postpartum

Liup

to1,200mg/day

Responded

tolithium

with

in10

days

ofinitiating

treatm

entandrecoveredwith

inamonth

Alsohadahistoryof

GM2

Ganglio-sidosis

MarshallandNursing

care

study1981

Casestudy

One

UK

wom

anwith

onsetof

psychosis8days

postpartum

CPZtablets(25mg,

bid)

andlorazepam

tablets

(2.5

mg,

bid)

Changed

toCPZtablets(50mg,

bid)

andim

ipraminetablets(25mg,

tid)

CPZandlorazepam

was

noteffective.

Increaseddose

ofCPZcombinedwith

imipraminedecreased

symptom

swith

in1weekandremainedsymptom

free

at12

week

Murray1990

Casestudy

One

UK

wom

anwith

onsetof

psychosis5days

postpartum

after1s

t

pregnancyand9days

postpartum

after2n

d

CPZ50

mg,

tidSym

ptom

sim

proved

rapidlywith

CPZafterboth

pregnancies

Study

isalso

included

under

thepreven-tionof

PP

O’Reagan1981

Casestudy

One

Canadianwom

anwith

onsetof

psychosis11

days

postpartum

Antipsychotics,ECT,

antid

epressants,andLi

Propranolol

(adrenergicblocking

agent)up

to450mg/day

ECTprovided

good

results,temporarily

Antipsychotics,

antid

epressants,andLihadno

effect

Propranolol

“cured”patient’spsychosis

Antipsy-chotic

and

antid

e-pressantdrugs

notspecified

Reedet

al.1999

Retro-spective

case-notestudy

114wom

enfrom

theUK

PPwith

in3months=

58Non-postpartum

psychosis=

56Postpartum

group=3–6ECTsessions

Non-

postpartum

group=1–23

ECTsessions

Wom

enwho

experiencedPPhadsignificantly

greater

clinical

improvem

entfollo

wingECTcomparedto

thenon-postpartum

psychosisgroup

Silb

ermann

etal.1975

Prospectiv

estudy

Com

pari-son

group

was

retro-spectiv

e

19wom

enfrom

theNetherlands

experiencing

postpartum

delirium

Treatmentgroup(13/19)=

combinatio

nof

Li

(upto

1,200mg/d)

andperfenazine(upto

30mg/d)

Com

parisongroup(6/19)=oneor

moreantip

sychotics

The

treatm

entgroupwas

symptom

free

with

in7–15

days,

less

likelyto

relapse,

andhadsignificantly

faster

recovery

times

(mean12

weekcomparedto

20week)

Onset

timenotspecified

Stanw

orth

1982

Casestudy

1wom

anfrom

theUK

with

onsetof

psychosis

1weekpostpartum

CPZ(upto

250mg/day)

2ECTtreatm

ents

Little

improvem

entwith

CPZalone.

Goodim

provem

ent

with

CPZandECT

Steiner

etal.1973

Openclinical

trial,

con-secutiv

eassignmentto

1of

2treatm

entgroups

10wom

enfrom

Israel

with

psychosisassociated

with

child

bearingMeanonsettim

eforthe

propranololgroupwas

14days

and35

days

fortheCPZgroup

Propranolol

(upto

3,200mg/d)

=5/10

CPZ

(upto

800mg/d)

=5/10

Bothtreatm

entseffective;

however,wom

entreatedwith

propranololweredischarged

sooner,hadgreater

symptom

improvem

ent,andsymptom

sim

proved

morerapidlyas

measuredby

theBRPSandtheCGI

Usedmeanonsettim

e;howeverrangenotspecified

Targum

etal.1979

Caseseries

TwoUSwom

enwith

ahistoryof

bipolardisorder

with

onsetof

PP

with

in2weeks

postpartum

(after

with

draw

alfrom

Liduring

pregnancy)

Case1:

treatedwith

thioridazine

for1weekandrestarted

onLiCase2:

treatedwith

CPZandrestartedon

Li

Bothcasesrecoveredwith

in17

days

BPRSBrief

Psychiatric

RatingScale,ICD

InternationalClassificationof

Diseases,CGIcogn

itive

glob

alim

pression

,PPpo

stpartum

psycho

sis,PPD

postpartum

depression

,CPZchlorpromazine,

ECTelectrocon

vulsivetherapy,

Lilithium

,CBZcarbam

azepine,

HRTho

rmon

ereplacem

enttherapy

Prevention and treatment of postpartum psychosis 93

Function, and the Asberg Side Effects Scale. Within20 weeks postpartum, 10 (67%) of the 15 women whoreceived divalproex relapsed, compared to eight (73%) ofthe 11 unmedicated women. There were no significantdifferences between the two groups. While divalproex wasnot effective, none of the women who relapsed experienceda severe episode that required admission, which may beassociated with the close clinical supervision of theparticipants.

Overall, prophylactic lithium was supported in fivestudies (Austin 1992; Cohen et al. 1995; Stewart 1988;Stewart et al. 1991; van Gent and Verhoeven 1992). Theprophylactic effects of carbamazepine were demonstrated intwo studies (Cohen et al. 1995, van Gent and Verhoeven1992), while prophylactic divalproex was not supported inone study (Wisner et al. 2004).

Antipsychotics Only one study to date has explored theeffects of antipsychotics for the prevention of PP. An opentrial exploring the effects of prophylactic olanzapine wasconducted in Canada including 25 women with a history ofbipolar disorder, of which 11 received olanzapine alone orin combination with an antidepressant or mood stabilizer,while 14 received either antidepressants, mood stabilizers,or no medication (Sharma et al. 2006). The treatmenteffects were assessed using the Schedule for AffectiveDisorders and Schizophrenia—Lifetime Version, the HamiltonRating Scale for Depression—31 items, the Young ManiaRating Scale, and the Personal Mood Diary. At 4 weekspostpartum, only two (18%) of the 11 women who receivedolanzapine experienced an affective relapse according to theDSM-IV criteria, in comparison to eight (57%) of the 14 whodid not receive olanzapine.

Hormone therapy Three studies reported the effects ofhormone therapy for the prevention of psychosis postpar-tum. To determine the effects of prophylactic oral estrogen,an open clinical trial was conducted with 11 US womenwho had a history of either PP or postpartum depression(Sichel et al. 1995). None of the 10 women who compliedwith the estrogen treatment relapsed. The preventive effectsof estrogen were less promising in an open clinical trialwith 29 pregnant women from the UK who met the RDCfor hypomania, mania, or schizoaffective disorder (Kumaret al. 2003). The Schedule for Affective Disorders andSchizophrenia–Lifetime Version was used to assess thetreatment effects of prophylactic transdermal estrogen thatwas administered 48 h after birth in doses of 200, 400, or800 μg/day. Estrogen was not effective in reducing the rateof relapse; however, of the 12 out of 29 who relapsed, thosewho received a dose of 800 μg/day required less subse-quent psychotropic medication and recovered sooner. In acase study with a woman from the UK, prophylactic

progesterone administered during pregnancy and postpar-tum was not effective in preventing a relapse of PP (Murray1990). In summary, there are mixed findings for thepreventative effects of estrogen and there is no evidenceto support the prophylactic use of progesterone.

Treatment of PP

Research on the treatment of PP has examined the effects ofelectroconvulsive therapy (ECT), antipsychotics, moodstabilizers, hormones, and the beta-blocker propranolol.The sample size for the 17 treatment studies and casereports ranged from 1 to 114, with 15 (88%) studiesincluding 10 or fewer participants; over half (53%) of thestudies had only one participant. Not surprising, themajority (76%) of treatment studies were case reports.

Electroconvulsive therapy Three studies have explored theeffects of ECT in the treatment of PP. In a retrospectivestudy with 114 women, UK researchers compared theclinical response to ECT in women with postpartum andnon-postpartum psychosis (Reed et al. 1999). According toblind ratings, the postpartum group was found to havegreater clinical improvement following ECT compared tothe non-postpartum group. In a case study of a woman fromthe UK, treatment with chlorpromazine alone resulted inlittle clinical improvement, while the addition of ECTresulted in positive outcomes (Stanworth 1982). Anothercase study described five US women who had severe andtreatment refractory PP or depression with onset between3 weeks and 11 months postpartum (Forray and Ostroff2007). All women were treated with ECT and improvedwithin three to six sessions. Overall, these studies providebeginning support for the beneficial effects of ECT in thetreatment of PP.

Mood stabilizers Three studies have examined the effectsof lithium in the treatment of PP. A case study of an Israeliwoman revealed a positive response to lithium within10 days of initiating treatment and patient recovery within amonth (Lichtenberg et al. 1988). The woman also had ahistory of GM2 Gangliosidosis, wherein approximately onethird who have this disorder also experience psychosis. Aprospective study of 19 women from the Netherlandscompared the treatment effects of a group who receivedlithium combined with perfenazine to a group who receivedone or more antipsychotic treatments (Silbermann et al.1975). The lithium treatment group was symptom freewithin 7–15 days, was less likely to relapse, and hadsignificantly faster recovery times, with a mean of 12 weekscompared to 20 weeks. In a case study, two US womenwith a history of bipolar disorder experienced PP within

94 S. Doucet et al.

2 weeks postpartum (Targum et al. 1979). One woman wastreated with lithium and thioridazine and the other womanwith lithium and chlorpromazine. Both women recoveredwithin 17 days. In summary, there have been very fewstudies examining the effect of lithium. This treatmentoption was found to be effective in one case study where itwas used as monotherapy (Lichtenberg et al. 1988) and intwo studies where it was used as adjunct therapy (Silbermannet al. 1975; Targum et al. 1979).

Antipsychotics The effects of antipsychotics in the treat-ment of PP have been examined in four studies. Onestudy described a UK woman who experienced PP aftertwo separate pregnancies and reported that treatment withchlorpromazine was successful during both episodes(Murray 1990). In another case study with a UK womanexperiencing PP, chlorpromazine combined with loraze-pam was ineffective (Marshall and Nursing Care Study1981). However, when chlorpromazine was increased andcombined with imipramine, the woman’s psychotic symp-toms decreased within 1 week and she remained symptomfree at 12 weeks.

In a case study of a woman from Germany with PP,treatment with clozapine was effective within a week(Kornhuber and Weller 1991). In another case study, aSpanish woman was refractory to treatment with variousdrugs, including antidepressants, anxiolytics, and the anti-psychotics haloperidol and methotrimeprazine (Iruela et al.1992). Another antipsychotic, pimozide, was administeredand was effective within 4 days. Overall, very few studieshave explored the effects of antipsychotics in the treatmentof PP. There are reports of successful treatment withchlorpromazine, clozapine, and pimozide.

Hormone therapy Five studies have examined the effects ofhormonal treatment among women diagnosed with PP.Three studies conducted in Finland examined the treatmenteffects of sublingual estrogen in women who had estrogendeficiency and PP (Ahokas and Aito 1999; Ahokas et al.2000a; Ahokas et al. 2000b). A total of 14 women weredescribed in the three reports. Using the Brief PsychiatricRating Scale (BPRS), psychiatric symptoms were reportedto have decreased within 2 weeks of estrogen treatment.Four women discontinued their estrogen treatment andexperienced a relapse within 2 weeks. The case study of awoman from the UK reported a positive outcome for theeffects of progesterone in the treatment of PP after thewoman did not respond to an unspecified tranquilizer(Atkinson and Atkinson 1983). In a recent case study, aTaiwanese woman with a history of mania was treated forPP with hormone replacement therapy, which consists ofestrogen and progesterone (Huang et al. 2008). Thistreatment was reported to be effective within 2 weeks after

the woman was refractory to antipsychotics and moodstabilizers. With only a few individual case reports, it is notpossible at present to conclude that any evidence exists forthe hormonal treatment of PP.

Propranolol This drug is a beta-adrenergic blocker that isprimarily used to treat hypertension (Prichard and Gillam1996). Propranolol was first used to treat PP in 1973(Steiner et al. 1973), although the mechanism in whichpropranolol works on treating psychiatric conditions is notwell understood. To compare the effects of propranolol andchlorpromazine, an open clinical trial was conducted with10 Israeli women experiencing PP (Steiner et al. 1973).Both treatments were effective in reducing the severity ofpsychotic symptoms as measured by the BPRS and theCognitive Global Impression (CGI) instruments; however,women treated with propranolol were discharged sooner(61 days compared to 104 days), symptoms improved morerapidly (3 days compared to 55 days), and demonstratedgreater mean improvement on the BPRS and the CGI. Theuse of propranolol was also supported in a case study of aCanadian woman who was unresponsive to antipsychotics,antidepressants, lithium, and ECT (O’Reagan 1981). Pro-pranolol was said to have “cured” the patient’s psychosis.Overall, only two studies to date have supported the effectsof propranolol in the treatment of PP (O’Reagan 1981;Steiner et al. 1973).

Discussion

The aim for this systematic review was to examine theeffectiveness of interventions for the prevention andtreatment of PP. A total of 26 studies were reviewed, with10 examining preventative interventions and 17 examiningtreatment interventions (one study included both preventionand treatment interventions). Studies were conducted innine countries, with the majority conducted in the UK(33%), followed by the US (19%). The years of publicationfor the included studies ranged from 1973 to 2008, whileapproximately two thirds (65%) of the studies werepublished more than 10 years ago. The methodologicalquality of the studies differed significantly, resulting in alimited evidence base to guide current practice and decisionmaking. In particular, the study sample sizes were generallysmall, reports were often retrospective, and the designswere primarily case reports. While the evidence providedfrom this research is limited, it does highlight promisingareas for additional research and may provide clinicianswith some suggestions to guide management. In addition,for some treatment approaches with a considerable evi-dence base in non-postpartum samples—mood stabilizers

Prevention and treatment of postpartum psychosis 95

and antipsychotics for example—further evidence in post-partum cases may be reassuring. For novel treatmentoptions such as hormonal manipulation, however, the lackof data is far more concerning reflecting the need foradditional research before conclusions about efficacy canbe drawn. Overall, further research is warranted usingrigorous methodology to evaluate current preventative andtreatment options.

The studies included in this review used a variety ofdiagnostic criteria to determine participant study inclu-sion and intervention efficacy. The standardized diagnos-tic criteria used for inclusion in the preventative studiesincluded the DSM III (van Gent and Verhoeven 1992),DSM III-R (Cohen et al. 1995; Sichel et al. 1995), DSM-IV (Sharma et al. 2006; Wisner et al. 2004), and the RDC(Austin 1992; Kumar et al. 2003; Stewart et al. 1991).Five prevention studies used standardized questionnairesto determine the relapse of postpartum psychosis, includ-ing the Schedule for Affective Disorders and Schizophre-nia—Lifetime Version (Kumar et al. 2003; Sharma et al.2006), the Mania Rating Scale (Wisner et al. 2004), theYoung Mania Rating Scale (Sharma et al. 2006), theBech–Rafaelson Mania Scale (Wisner et al. 2004), theHamilton Rating Scale for Depression (Sharma et al. 2006;Wisner et al. 2004), the Global Assessment of Function(Wisner et al. 2004), the Asberg Side Effects Scale(Wisner et al. 2004), the Personal Mood Diary (Sharmaet al. 2006), the DSM III-R checklist (Sichel et al. 1995),the Structured Clinical Interview for DSM-IV (Wisner etal. 2004), and a “standard data form” (Stewart et al. 1991).Only one treatment study (Ahokas et al. 2000a) reportedusing standardized diagnostic criteria to diagnose postpar-tum psychosis, namely the ICD-10. Questionnaires wereused to assess the treatment effects in seven studies;specifically the BPRS (Ahokas and Aito 1999; Ahokas etal. 2000b; Steiner et al. 1973), the CGI (Steiner et al.1973), and various unstandardized scales (Forray andOstroff 2007; Reed et al. 1999; Silbermann et al. 1975).Overall, eight of the prevention studies and only seven ofthe treatment studies used some form of a standarddiagnostic assessment. The diagnostic measures werediverse, making comparisons between studies difficult tointerpret. Moreover, the studies included in this reviewrepresent a variety of prevention and treatment approachesin various combinations, further precluding any clearcomparisons between studies. For these reasons, resultsfrom this review should be interpreted with caution.

Prevention

Research on the prevention of PP has focused on the effectsof mood stabilizers, antipsychotics, and hormone therapy.Lithium was the most commonly studied prevention

approach with research suggesting it may decrease the rateof relapse from approximately 50% to less than 22%(Austin 1992; Cohen et al. 1995; Stewart 1988; Stewart etal. 1991). Further support for the use of lithium comes fromstudies demonstrating high relapse rates among womenwho discontinue their lithium during pregnancy (Targum etal. 1979; Viguera et al. 2000). There is insufficient evidenceto suggest whether lithium is equally effective whenadministered prophylactically through pregnancy or startedimmediately in the postpartum period.

Only one study has focused on the effects ofantipsychotics in the prevention of PP and positiveresults have been found in a small trial of olanzapine(Sharma et al. 2006). Additional research is clearlyrequired, but the dearth of evidence for prophylacticantipsychotic medication in the postpartum context mustbe considered in light of the more robust evidence base forthese medications in non-postpartum samples. In the caseof hormonal prophylaxis, however, the evidence base ispoor and without the studies demonstrating efficacy inmood disorders more generally there is insufficientevidence to support their use at present. What is veryclear is that women with a history of PP or bipolardisorder who do not receive prophylactic treatment are atan increased risk for relapse of affective symptoms (Austin1992; Cohen et al. 1995). Larger naturalistic and possiblyrandomized controlled trials are required to examine theeffects of prophylactic interventions.

Treatment

Research on the treatment of PP has examined the effects ofECT, mood stabilizers, antipsychotics, hormones, andpropranolol. The limited evidence supports the use ofECT in the treatment of PP when administered alone(Forray and Ostroff 2007; Reed et al. 1999), as well aswhen combined with the antipsychotic chlorpromazine(Stanworth 1982). Overall, the use of antipsychotics in thetreatment of PP requires further investigation before anyconclusions can be drawn about their effectiveness postna-tally. Their use at this time, however, must be considered inlight of the large body of evidence of efficacy in non-postpartum episodes.

Lithium is commonly used in the treatment of PP;however, the evidence to support this treatment option isscarce. In the few studies conducted to date (Lichtenberg etal. 1988; Silbermann et al. 1975; Targum et al. 1979),lithium treatment for PP is generally supported. Theeffectiveness of lithium in the treatment of bipolar disorderis well documented and it has been suggested that lithium isequally effective with postpartum women as it is with non-postpartum women (Abou-Saleh and Coppen 1983). Fur-ther comparative investigations are needed that examine

96 S. Doucet et al.

whether the effects of lithium are equally effective intreating episodes of PP.

Three studies conducted by the same group (Ahokas andAito 1999; Ahokas et al. 2000a, b) have found beneficialeffects of estrogen. The potential beneficial use of proges-terone (Atkinson and Atkinson 1983) and hormone replace-ment therapy (Huang et al. 2008) were described throughcase studies. There is insufficient research to recommendhormone treatment; however, preliminary results wouldsuggest that further studies are indicated—particularly asthe involvement of hormonal factors in etiology come to bebetter understood.

There is an array of differences reported across studieson the effect of interventions for PP. Health professionalsshould therefore gain knowledge on what methods havebeen effective for women in the past and if any adverseeffects were experienced (Sharma 2003). Although we havefocused in this review on biological approaches, treatmentshould also go beyond the medical symptoms and includepsychosocial and psychological therapy given the complexand multiple needs of women diagnosed with PP.

Safety of medication during pregnancy and breastfeeding

An important consideration is the reproductive safety ofmedication in pregnancy and breastfeeding. While beyondthe scope of this review, there is clearly a need to conduct arisk benefit analysis with each individual woman. Althoughsome medications are associated with particular problems,there are no universal recommendations that can be madeabout whether to continue or stop and the decision mustultimately lie with the woman and her family. Moreover,women with bipolar disorder need to be informed early intheir illness about the risks in childbirth and the reproductivesafety of medication and family planning should be discussedwhen drugs are prescribed.

Limitations

The review only included studies published in English.Although most cases of PP occur within the first 2 weeksafter giving birth (Heron et al. 2007), we included onsetwithin 1 year postpartum. In 10 (38%) of the studiesincluded in this review, women had onset times beyond2 weeks postpartum. This may preclude any clear inferencesto be made about the participants who exceeded 2 weeks inonset, as they may be cases that are coincidentally psychoticin the postpartum period, and not truly cases of PP.

Implications for future research

There are numerous gaps in the research on strategies toprevent and treat PP. Agreement is needed on the diagnosis

and classification of the disorder that is not dealt with in aparticularly helpful way in current DSM-IV and ICD-10criteria. While acquiring large representative samples andconducting randomized controlled trials is problematic,collaborative multicenter naturalistic studies are possibleand would provide very helpful data.

Future research could also focus on gaining a betterunderstanding of the causes of PP, as this will act as a guidefor research on prevention and treatment. Given the equivocalevidence on hormone therapy in both the prevention andtreatment of PP, research on the etiology of PP could furtherexamine the role of hormonal factors to guide management.

Conclusion

Firm recommendations on effective interventions arelimited until further research is conducted on all forms ofprevention and treatment for PP. PP represents a psychiatricemergency, thus the timely recognition of symptoms andearly treatment is critical to the well-being of the affectedwoman and her family. The well-established risk factors(e.g., bipolar disorder) and potentially severe consequences(e.g., suicide and infanticide) of PP point to the importanceof preventive measures. Multicenter prospective studies aredesperately needed to provide guidance on prevention andtreatment interventions.

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