Journal of Psychiatric and Mental Health Nursing, 2010, 17, 97104

Antipsychotics in pregnancy

jpm_1481

97..104

K . M C C A U L E Y- E L S O M 1 r m m h n m n p h d , C . G U RV I C H 2 d p s y c h ,
S. J. ELSOM3 rn phd & J. KULKARNI4 mbbs phd
1

Senior Lecturer Midwifery and Mental Health Nursing, School of Nursing and Midwifery, Monash University,
Research Fellow, 4Director/Professor, Monash Alfred Psychiatry Research Centre, Monash University, and
3
Director/Associate Professor, Centre for Psychiatric Nursing, University of Melbourne, Vic., Australia
2

Keywords: atypical antipsychotics,

pregnancy, women
Correspondence:
K. McCauley-Elsom
School of Nursing and Midwifery
Peninsula Campus
Monash University
McMahons Road
Frankston
Vic. 3199
Australia
E-mail:
kay.mccauley@med.monash.edu.au
Accepted for publication: 6 July 2009
doi: 10.1111/j.1365-2850.2009.01481.x

Accessible summary

This article summarizes the literature relating to the use of antipsychotics in pregnancy with a focus on the most commonly used atypical antipsychotics.
Discusses other key factors to be considered when using these medications in
pregnant or lactating women.
Recognizes the contribution of pregnancy registers in gathering data to provide
guidance to clinicians about the psychopharmacological management of women
with serious mental illness.

Abstract
Women who are pregnant and who have a history of psychosis are commonly managed
with antipsychotic medications. The evidence regarding the use of antipsychotics in
pregnancy has been insufficient to provide adequate support for this practice and is a
concern for clinicians and women alike. This review presents literature surrounding the
use of antipsychotic medications in pregnancy, providing an overview of the historical
and contemporary perspectives which influence clinicians prescribing practices. Data
were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics
with pregnancy and psychosis or schizophrenia. This was expanded to include the
most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine,
ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic
medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors reviews of the literature, case studies, retrospective reports,
drug company registries and more recently a prospective comparative study. This
review identifies that the literature provides no clear answer for clinicians as to the
risk associated with the use of antipsychotics in pregnancy. To this effect, recently in
Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby,
when antipsychotic medications have been used during pregnancy.

Introduction
Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications (McKenna et al. 2004). Exposure to antipsychotic
medication during pregnancy is associated with potential
obstetric, teratogenic, neurobehavioural and neonatal
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risks of toxicity (Littrell et al. 2000, McKenna et al. 2004,

Trixler et al. 2005). These risks must be weighed up against
the risks associated with medically untreated psychosis to
both the mother, and her ability to mother. The evidence
regarding the use of atypical antipsychotic medications
in pregnancy has been insufficient to provide adequate
support for this practice and is a concern for clinicians
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K. McCauley-Elsom et al.

and women (Pinkerton et al. 1997, Dickson & Hogg 1998,

MacKay et al. 1998, Gentile 2004, Usher et al. 2005).
Despite limited evidence about safety and efficacy, clinicians prescribe antipsychotics for pregnant women with
psychosis. Since the introduction of atypical antipsychotic
medications, pregnancy rates in women with schizophrenia
have increased (McKenna et al. 2004) and women are commonly prescribed atypical antipsychotics during pregnancy
(Littrell et al. 2000, McKenna et al. 2004, Trixler et al.
2005). Clinically, the challenge for clinicians and women is
to consider and weigh up the risk to the mothers mental
health and well-being against possible risk of abnormalities
to the foetus and developmental problems in the infant.
This is particularly difficult where views about the safety of
antipsychotic use in pregnancy and postpartum remain
contradictory, with limited evidence regarding the use of
these medications (Pinkerton et al. 1997, Dickson & Hogg
1998, MacKay et al. 1998, Gentile 2004, Usher et al.
2005). While there have been many literature reviews of
the evidence related to this topic, gathering evidence in the
form of randomized controlled trials is a slow process and
in the interim clinicians need support when confronted
with such dilemmas (Potts et al. 2006).
The women most likely to be prescribed antipsychotic
medications during the perinatal period (conception to 1
year after birth) consist of four groups including those who
wish to become pregnant, those who become pregnant
while taking medication, those who become mentally ill
while pregnant, and those women who become unwell
postnatally (Craig & Abel 2001). Various guidelines
regarding the use of antipsychotic medications during the
perinatal period have been produced (Gentile 2004), which
generally recommend cautious use and indicate a careful
assessment of the benefits and risks which must be applied
to each womans situation and also each antipsychotic
(Trixler et al. 2005). Current clinical practice varies. This
variation in practice is attributable to clinicians awareness
of the lack of substantial evidence and their uncertainty
that treatment will work and, at the same time, will cause
no harm to either mother or baby (Potts et al. 2006). While
many clinicians are maintaining women on the newer
atypical antipsychotics, some are taking them off these
and others introducing the older typical antipsychotics in
the belief that they are safer. The confidence of clinicians
gained from their previous experience and recommendations found in the literature at the time.
The most current recommendations for clinicians in
Australia come from the Maternal Mortality 20002002
report (Australian Institute of Health and Welfare,
National Perinatal Statistics Unit 2006) which identifies the
rates of maternal suicide in Australia over that period and
encourages the maintenance of women on their existing
98

antipsychotic. However, the literature is less absolute about

making such a recommendation. The use of psychotropic
medications during pregnancy is described as appropriate
in clinical situations where the risk of prenatal exposure is
outweighed by the risk of relapse following drug discontinuation (Altshuler et al. 1996, Trixler & Tenyi 1997).
Other authors argue that medication should only be prescribed when absolutely necessary (Oates 1989) and if a
woman can do without it, it would be appropriate to
discontinue it at the time her pregnancy is confirmed
(Cohen 2005) or at 2 weeks prior to the birth of the baby
to reduce the risk of medication effects on the baby, though
stopping the medication increases the risk of relapse
(Pinkofsky 1997). To establish the current practice related
to the use of atypical antipsychotic medications in pregnancy a National Register has been established to provide
data on pregnancy, birth and postpartum outcomes of
women across Australia (McCauley-Elsom & Kulkarni
2007, Kulkarni et al. 2008).
Antipsychotic medications available are defined as first
generation, including low potency medications such as
chlorpromazine or high potency agents such as haloperidol, and second generation or atypical antipsychotics. To
date there is no conclusive evidence of an increased risk of
malformations with the second generation antipsychotics
(Altshuler et al. 1996, McKenna et al. 2005, Yaegar et al.
2006). In a prospective comparative study of pregnancy
outcomes of women using second generation antipsychotic
drugs, McKenna et al. (2005) reported that of 110 pregnant women exposed to a second generation antipsychotic
the only statistically significant difference in pregnancy
outcomes was low birth weight babies in 10% of those
exposed to second generation antipsychotics compared
with 2% in the comparison group of women not taking
antipsychotic medication. Reports of safety for the foetus
and baby with the use of both the first generation and
second generation antipsychotics vary across the spectrum
ranging from no or low risk (Altshuler et al. 1996, MacKay
et al. 1998, Hill et al. 2000, Nagy et al. 2001, Koren et al.
2002, Goldstein et al. 2004, Yaris et al. 2004, McKenna
et al. 2005); some risk (Sacker et al. 1996, Cohen &
Rosenbaum 1998, Pinkofsky 2000) to high risk (Dev &
Krupp 1995, Howard et al. 2004). Others say the risks are
uncertain (Ernst & Goldberg 2002). This review provides
an outline of the current evidence regarding the use during
pregnancy of each of the most commonly prescribed atypical antipsychotic medications including olanzapine, clozapine, risperidone, quetiapine and aripiprazole (Altshuler
et al. 1996, Eberhard-Gran et al. 2005). While current
practice is known to vary according to the clinicians experience in managing women with psychosis in pregnancy
and their access to current reports from government
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Antipsychotics in pregnancy

policies and literary sources, the most current recommendations do encourage the maintenance of woman on her
medications for the best outcomes overall.

Method
The electronic databases Medline (1950 to present),
CINAHL (1982 to present) and PsycINFo (1967 to
present) were searched using both title and keyword
searches, individually and combined. It was interesting; in
searching these databases the earliest reports of the use of
antipsychotic medications in pregnant women were identified and reflect the history of such use and the development
in antipsychotic medications over the decades. Initial
search terms included antipsychotics (including specific
searches for the currently most commonly used atypical
antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole), psychosis or schizophrenia in combination with pregnancy, postpartum and
breastfeeding. Papers were selected based on the abstracts.
All papers available were accessed, similarly to Gentile
(2008). The reference lists of articles (including review
papers) were scanned for any further literature that had not
been discovered in the initial search. This initial strategy
yielded over 2000 potentially relevant articles. After
reading of abstracts or full-text articles, those reporting
primary data were included and once again the reference
lists of each were examined for further important works.
Secondary citations were excluded. Due to the paucity of
well-designed prospective studies, particularly in relation
to the newer agents, a formal appraisal of levels of evidence
was not conducted. Where case reports, pharmaceutical
company registries and other smaller studies have been
included, the limitations of this evidence are noted. Search
was last updated in November, 2007.

Olanzapine
At present, the most commonly reported atypical antipsychotic used in pregnancy is olanzapine (Littrell et al. 2000,
Friedman & Rosenthal 2003, Goldstein et al. 2004). A
number of case studies have described the successful use of
olanzapine in pregnancy. Friedman & Rosenthal (2003)
reported on a woman diagnosed with delusional disorder
and borderline personality disorder taking olanzapine
during pregnancy. While her infant was large for gestation
and had Erbs Palsy (which subsequently resolved), it was
healthy at 6 months and the womans psychotic symptoms
did not recur. Mendhekar et al. (2002) also reported a
successful case of a woman treated with olanzapine. The
woman had a previous history of psychotic episodes in
pregnancy and postpartum. She developed a psychosis
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during her recent pregnancy and was medicated with olanzapine from 24-week gestation. Her condition improved
and the olanzapine was slowly reduced and ceased 2 weeks
prior to delivery. She delivered a normal healthy male baby
at full term.
Littrell et al. (2000) described the case of a woman with
schizophrenia with a complex history of 30 hospitalizations and treatment with nine different antipsychotics. She
was prescribed olanzapine when she planned for and
became pregnant. Although her pregnancy was complicated by hypertension, weight gain and pre eclampsia, she
delivered a normal female baby at 30 weeks by caesarean
section. There were no exacerbations of psychosis during
the perinatal period and while the authors felt her physical
complications were primarily pregnancy related, the contribution of olanzapine was not ruled out. Interestingly,
in his review article, Gentile (2006a) reported an apparent
association between the use of olanzapine and maternal
weight gain, metabolic disorders such gestational diabetes
and the consequences of foetal macrosomia and shoulder
dystocia at birth.
Larger studies on olanzapine during pregnancy include a
review of 23 prospectively ascertained pregnancies and 13
retrospective cases of exposure to olanzapine (Goldstein
et al. 2004). Of the 23 prospectively cases the rates for
spontaneous abortion (13%), stillbirth (5%), prematurity
(5%) and major malformation (0%) were within the
normal range. In one study (McKenna et al. 2005) foetal
malformations in one baby, exposed to olanzapine,
included multiple anomalies; however, the authors noted
that the rate of major malformations was not significantly
different to those who were not exposed to antipsychotic
medications. In summary, there is no clear evidence that
women taking olanzapine during pregnancy have any
greater risk of adverse events than the general population
of pregnant women (McKenna et al. 2005, Gentile 2006a).
However, risks of weight gain and associated metabolic
syndrome have been reported in association with olanzapine, as well as other atypicals including clozapine and
quetiapine (Newcomer 2007).

Clozapine
While not a first line treatment, clozapine is commonly
used during pregnancy. While results from animal studies
that failed to demonstrate risk have formed much of the
basis for suggesting clozapine is safe during pregnancy
(Iqbal et al. 2003), the safety, course and outcome of pregnancy in women treated with clozapine has been described
in a number of case studies (Dev & Krupp 1995, McKenna
et al. 2005). Several authors report cases of neonatal convulsions and floppy baby syndrome in women taking
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K. McCauley-Elsom et al.

clozapine during pregnancy (Altshuler et al. 1996, Cohen

& Rosenbaum 1998, Yaegar et al. 2006). In contrast, the
successful use of clozapine was described in the case of a
pregnant woman with a history of schizophrenia (Yogev
et al. 2002). While in labour a decreased variability was
noted on cardio tocograph trace of foetal heart, the baby
was delivered at 37 weeks gestation with normal birth
weight and apgar scores an initial assessment of the
newborn (Finster & Wood 2005); the authors suggested
that clozapine may have affected the foetal central nervous
system. A recent case of a woman taking clozapine
described no perinatal complications; and although not
conclusively associated with use of clozapine during pregnancy, it was noted that the child developed speech problems (Mendhekar 2007).
There are also reports associating clozapine with gestational diabetes. An early report (Dickson & Hogg 1998)
described a woman with treatment resistant schizophrenia
who became pregnant after changing from a typical antipsychotic to clozapine. Clozapine was thought to be a contributing factor in enabling this pregnancy, which was also
complicated by gestational diabetes (Dickson & Hogg
1998). In a report of six cases of pregnant women who
received clozapine, using the pharmacovigilance and epidemiology service in Switzerland (Nguyen & Lalonde 2003),
one woman developed gestational diabetes due to her
bodyweight in one of her two pregnancies. In her second
pregnancy she was not obese and did not develop the
complication. Both babies were delivered at term and were
healthy at 5 and 3 years. In summary, there is no conclusive
evidence regarding the safety or risks associated with
Clozapine use for pregnant women.

Risperidone
The wide-spread use of Risperidone, being one of the earliest
atypical antipsychotic medications, has generated a substantial amount of literature. A recent article reported a successful outcome for both mother and baby with the maintenance
of risperidone during pregnancy (McCauley-Elsom &
Kulkarni 2007); however, cessation of medication in the
postpartum resulted in relapse. In a post marketing study by
MacKay et al. (1998) nine women took risperidone during
10 pregnancies; seven of these were live births and three
were terminated. While no abnormalities were reported in a
further seven babies exposed to risperidone in pregnancy,
results from this small sample do not permit conclusions to
be drawn (Trixler et al. 2005). There were also no reports of
congenital abnormality reported from the 49 cases in a
larger study (McKenna et al. 2005, Yaegar et al. 2006).
Reports related to the use of risperidone in pregnancy
describe rates of adverse events during pregnancy and
100

foetal anomalies that were consistent with rates in the

general population (Coppola et al. 2007). Coppola et al.
(2007) concluded that exposure to risperidone in pregnancy does not appear to increase the risk of spontaneous
abortions, congenital abnormalities or teratogenic risk to
the foetus. While some extra-pyramidal effects were
described these were said to be self-limiting (Coppola et al.
2007). While little information regarding the use of injectable risperidone in pregnancy exists to date, a case study of
one woman is described with a normal pregnancy and
birth, and no evidence of congenital abnormality or developmental problems postnatally (Kim et al. 2007) and similarly by McCauley-Elsom & Kulkarni (2007). In summary,
the reports to date regarding the use of risperidone indicate
little risk with use in pregnancy.

Quetiapine
Quetiapine has been shown to improve a womans mental
illness following a change of medications from zuclopenthixol (Tenyi et al. 2002). The use of quetiapine was
described in a pregnant woman who decided to continue
antipsychotic medication based on the level of risk and
family history of psychosis, as well as the absence of
reports at the time to suggest complications associated with
the use of quetiapine during pregnancy (Taylor et al. 2003).
The woman remained in remission throughout the pregnancy and gave birth to a healthy girl. Gentile (2006b) also
described a woman treated with quetiapine (in combination with fluozamine) during pregnancy and breastfeeding
without ill effect. While she had an elective caesarean delivery because of intrauterine myoma, she delivered a healthy
female baby and a good outcome was reported for mother
and baby (Gentile 2006b). Yaegar et al. (2006) discuss a
complex case where a woman had been successfully treated
with quetiapine prior to conceiving, at which point she
switched to olanzapine and experienced a marked deterioration in mental state. The woman and her partner decided
that her mental health was, on balance, as important as the
well-being of the foetus and, despite the lack of research
available; the decision was made to resume treatment with
quetiapine with good result. Overall in reports regarding
the safety of quetiapine in pregnancy most studies report
no adverse effects (Yaegar et al. 2006) or congenital abnormalities (Tenyi et al. 2002, Taylor et al. 2003, McKenna
et al. 2005, Gentile 2006b).

Aripiprazole and ziprasidone

There are few reports regarding the use of aripiprazole in
pregnancy. While one case of foetal tachycardia in labour
resulted in a caesarean section, no other adverse effects
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Antipsychotics in pregnancy

have been reported to date (Gentile 2006a, Mendhekar

et al. 2006). From a small, Australian data base there have
been two cases of high neural tube defects resulting in early
second trimester miscarriages in women receiving aripiprazole in pregnancy (Kulkarni et al. 2008). No cases of
ziprasidone use in pregnancy have been reported in the
literature to date.

depression, anxiety or mood stabilization can interact with

antipsychotics, as can treatments for medical disorders
such as asthma and hypertension (Seeman 2004). Gentile
(2006a) identifies a variety of prescribed medications
and illicit drugs which are commonly taken by pregnant
women. The use of analgesics and contraceptives are also
common in women and must be considered, along with the
possible side effects and interactions that could occur.

Other considerations
The management of the pregnant women with schizophrenia presents a dilemma for clinicians. Decisions regarding
the best form of treatment are complicated when there is a
requirement to medicate women who are acutely psychotic
in pregnancy. The management of the agitated or aggressive pregnant women is described in one study, a retrospective chart review of medication management of 80 cases
(Ladavac et al. 2007). These authors reported that haloperidol was the most commonly used antipsychotic, with
the addition of risperidone, olanzapine or ziprasidone as
well as benzodiazepines in some cases. While 47% received
an antipsychotic, a combined approach was used in 29%,
and benzodiazepines only a further 24%. It was recognized
that the choice of medication was guided by clinicians
knowledge and experience with the medications and the
scant information available, regarding their safety in pregnancy (Ladavac et al. 2007). Decisions regarding the best
form of treatment are complicated when there is a requirement to medicate women who are acutely psychotic in
pregnancy.
The issue of breastfeeding and the use of antipsychotic
medication has been well reported (Yoshida et al. 1998a,b,
Hill et al. 2000, Kirchheiner et al. 2000, Friedman &
Rosenthal 2003, Nordeng & Spigset 2003, Gentile 2004,
Misri et al. 2006). Successful use has been described in
relation to risperidone (Hill et al. 2000), olanzapine (Kirchheiner et al. 2000, Friedman & Rosenthal 2003) and quetiapine (Misri et al. 2006). However, while no association
has been reported between the babies development and the
exposure to antipsychotics used during breast feeding,
most the authors still advise caution. Gentile (2004) recommends that consideration should include the severity of
the illness; an evaluation of the risks and benefits; and
careful choice of medication. While this article does not
address the issue of use of antipsychotics during breastfeeding, a current summary is found in the literature (Usher
et al. 2005, Usher & Foster 2006).
A further consideration is related to the use of multiple
medications during pregnancy in cases where women are
required to take more than one antipsychotic for optimum
symptom control (Yaris et al. 2004) or are combined with
other medications. Medications such as those taken for
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Discussion and recommendations

There are many complex issues surrounding the management of women who have a history of psychosis and who
become pregnant. This paper presents a summary of the
literature that is available to guide clinicians in making
their clinical decisions about the use of antipsychotics in
pregnancy. The balancing of both the mental well-being of
the woman and the safety of her baby remains a complex
task for health professionals involved in the delivery of
mental health and maternity care. The key focus of this
review was to present the current literature relating to the
use of atypical antipsychotics found in use in the Australian
context.
The rapid development in pharmacotherapy has resulted
in a growing number of women with schizophrenia being
treated with antipsychotic medications during pregnancy
(Trixler et al. 2005). Women with schizophrenia previously
had a lower fertility rate; this was considered to be a side
effect of the typical antipsychotic medications (Jarskog
et al. 2000). The atypical antipsychotics are not associated
with this effect and consequently, more women using
atypical antipsychotic medications are becoming pregnant (McKenna et al. 2005). During pregnancy, women
are being maintained on typical and atypical antipsychotics
depending on the confidence of clinicians gained from previous experience and the literature available at the time.
More recent concerns relating atypical antipsychotic use
to weight gain and metabolic syndrome must be noted
by clinicians when considering their use in the pregnant
woman because of the possible consequences for both
mother and baby. Clinicians may use other interventions in
conjunction with use of antipsychotic medications, these
may include psychological therapies, while not the focus of
this review such therapies including cognitive behavioural
therapy may be part of the clinicians suite of management
approaches; psycho education, support groups and psychotherapies have been described (Talbot et al. 2005, Kreidler
2006). However, in the authors experience women seldom
report the use of such therapies as being part of their
treatment and management plan.
Meanwhile, for the clinician there remains insufficient
evidence relating to best practice in using antipsychotic
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K. McCauley-Elsom et al.

medication during pregnancy. While long-term studies

gathering controlled prospective data from large numbers
of women are required (Cohen 2005, Trixler et al. 2005),
randomized control trials or multi-centred cohort studies
are identified as neither ethical nor practical in this client
group (Nagy et al. 2001, Howard et al. 2004, Howard
2005). Establishing drug registers will help to identify the
risk and benefits to mother and baby and to determine
overall safety (on both foetal and later development) of
antipsychotic medication use during pregnancy (Cohen
2005, Trixler et al. 2005). In Australia, the establishment
of the National Register of Antipsychotic Medication in
Pregnancy aims to collect data regarding outcomes for
mothers and their babys related to the use in pregnancy of
antipsychotic medications (McCauley-Elsom & Kulkarni
2007, Kulkarni et al. 2008).
Sharing information on infant outcomes by clinicians
and researchers is essential. It is essential to develop current
guidelines to support clinicians in planning and delivery of
treatment to this vulnerable group of clients. Well meaning
but poorly coordinated decisions by health professionals
can result in sub-optimal outcomes for both mother and
baby.

Conclusion
Traditionally psychiatric medications were withheld
during pregnancy because of fear of teratogenic and other
effects. However, emerging literature around the safety of
the most commonly used psychiatric medications points to
low risk of foetal harm, with some evidence of no or a
small non-specific risk for organ malformation. This
current review finds no evidence that the use of second
generation antipsychotics in pregnancy is associated with
any greater risk of foetal abnormality than is found in the
general population.
Given the known negative consequences of relapse of
mental illness on outcomes for both mother and baby, and
in the absence of any evidence of adverse effects on the
foetus of second generation antipsychotics, the maintenance of antipsychotic medications during pregnancy is
recommended. In particular, the use of olanzapine, risperidone, clozapine and quetiapine without harm to the foetus
has been reported over several years. Clinicians need to be
alert to the possibility of gestational metabolic disorders
and education needs to be provided for the women in
relation to diet, exercise and general well-being.
There remains a clear need for further research to reassure both clinicians and consumers of the safety of antipsychotic treatments during pregnancy. While ethical
considerations limit the possibility of prospective controlled designs, the regular reporting of clinical cases
102

through the establishment of medication registers may be a

way forward.

Acknowledgments
The project from which this article is derived was supported by Australian Rotary Health Research Fund. Professional editing by Australian Consultancy, Lismore.

References
Altshuler L.L., Cohen L., Szuba M.P., et al. (1996) Pharmacologic
management of psychiatric illness during pregnancy. American
Journal of Psychiatry 153, 592606.
Australian Institute of Health and Welfare, National Perinatal
Statistics Unit (2006) Maternal Deaths in Australia 20002002.
Canberra: Australian Institute of Health and Welfare, National
Perinatal Statistics Unit.
Cohen L. (2005) Drugs, pregnancy and lactation: atypical antipsychotics. Available at: http://www.womensmentalhealth.org/
topics/pregnancy_lib_OB_atypicals.html (accessed 17 December
2005).
Cohen L.S. & Rosenbaum J.F. (1998) Psychotropic drug use
during pregnancy: weighing the risks. Journal of Clinical Psychiatry 59 (Suppl. 2), 1828.
Coppola D., Russo L.J., Kwarta R.F., et al. (2007) Evaluating
the postmarketing experience of risperidone use during pregnancy pregnancy and neonatal outcomes. Drug Safety 30,
247264.
Craig M. & Abel K. (2001) Prescribing for psychiatric disorders in
pregnancy and lactation. Best Practice and Research in Clinical
Obstetrics and Gynaecology 15, 10131030.
Dev V. & Krupp P. (1995) Adverse event profile and safety of
clozapine. Review of Contemporary Pharmacotherapy 6, 197
208.
Dickson R.A. & Hogg L. (1998) Pregnancy of a patient treated
with clozapine. Psychiatric Services 49, 10811083.
Eberhard-Gran M., Eskild A. & Opjordsmoen S. (2005) Treating
mood disorders during pregnancy. Drug Safety 28, 695706.
Ernst C.L. & Goldberg J.F. (2002) The reproductive safety profile
of mood stabilizers, atypical antipsychotics and broad spectrum
psychotropics. Journal of Clinical Psychiatry 63 (Suppl. 4),
4255.
Finster M. & Wood M. (2005) The Apgar score has survived the
test of time. Anaesthesiology 102, 855857.
Friedman S.H. & Rosenthal M.B. (2003) Treatment of delusional
disorder: a case report. International Journal of Psychiatry in
Medicine 33, 391394.
Gentile S. (2004) Clinical utilization of atypical antipsychotics
in pregnancy and lactation. Annals of Pharmacotherapy 38,
12651271.
Gentile S. (2006a) Prophylactic treatment of bipolar disorder in
pregnancy and breastfeeding: focus on emerging mood stabilizers. Bipolar disorders 8, 207220.
Gentile S. (2006b) Quetiapine-fluvoxamine combination during
pregnancy and while breastfeeding. Archives of Womens
Mental Health 9, 158159.
Gentile S. (2008) Antipsychotic therapy during early and late
pregnancy. A systematic review. Schizophrenia Bulletin 11 September 2008 127. doi:10.1093/schbul/sbn107
2009 Blackwell Publishing

Antipsychotics in pregnancy

Goldstein D.J., Corbin L.A. & Fung M.C. (2004) Olanzapineexposed pregnancies and lactation: early experience. Journal of
Clinical Psychopharmacology 20, 399403.
Hill R.C., McIvor R.J., Bach B., et al. (2000) Risperidone distribution and excretion into human milk: case report and estimated infant exposure during breastfeeding. Journal of Clinical
Psychopharmacology 20, 285286.
Howard L.M. (2005) Fertility and pregnancy in women with
psychotic disorders. European Journal of Obstetrics, Gynaecology, and Reproductive Biology 119, 310.
Howard L., Webb R. & Abel K. (2004) Safety of antipsychotic
drugs for pregnant and breastfeeding women with non-affective
psychosis. BMJ 329, 933934.
Iqbal M.M., Rahman A., Husain Z., et al. (2003) Clozapine: a
clinical review of adverse effects and management. Annals of
Clinical Psychiatry 15, 3348.
Jarskog L.F., Mattioli M.A., Perkins D.O., et al. (2000)
First-episode psychosis in a managed care setting: clinical management and research. American Journal of Psychiatry 157,
878884.
Kim S.W., Kim K.M., Kim J.M., et al. (2007) Use of long-acting
injectable risperidone before and throughout pregnancy in
schizophrenia. Progress in Neuro-Psychopharmacology and
Biological Psychiatry 31, 543545.
Kirchheiner J., Berghofer A. & Bolk-Weischedel D. (2000)
Healthy outcome under olanzapine treatment in a pregnant
women. Pharmacopsychiatry 33, 7880.
Koren G., Cohn T., Chitayat D., et al. (2002) Use of atypical
antipsychotics during pregnancy and the risk of neural tube
defects in infants. The American Journal of Psychiatry 159,
136137.
Kreidler M. (2006) Group therapy for survivors of childhood
sexual abuse who have chronic mental illness. Archives of Psychiatric Nursing 19, 176183.
Kulkarni J., McCauley-Elsom K., Marston N., et al. (2008) Preliminary findings from the National Register of Antipsychotic
Medications in Pregnancy. Australian and New Zealand
Journal of Psychiatry 42, 3844.
Ladavac A.S., Dubin W.R., Ning A., et al. (2007) Emergency
management of agitation in pregnancy. General Hospital
Psychiatry 29, 3941.
Littrell K.H., Johnson C.G., Peabody C.D., et al. (2000) Antipsychotics during pregnancy. American Journal of Psychiatry 157,
1342.
McCauley-Elsom K. & Kulkarni J. (2007) Managing psychosis in
pregnancy. Australian and New Zealand Journal of Psychiatry
41, 289292.
MacKay F.J., Wilton L.V., Pearce G.L., et al. (1998) The safety of
Risperidone: a post-marketing study on 7684 patients. Human
Psychopharmacology 13, 413418.
McKenna K., Einarson A., Levinson A., et al. (2004) Significant
changes in antipsychotic drug use during pregnancy. Veterinary
and Human Toxicology 46, 4446.
McKenna K., Koren G., Tetelbaum M., et al. (2005) Pregnancy
outcome of women using atypical antipsychotic drugs: a prospective comparative study. Journal of Clinical Psychiatry 66,
444449.
Mendhekar D.N. (2007) Possible delayed speech acquisition
with clozapine therapy during pregnancy and lactation.
Journal of Neuropsychiatry Clinical Neuroscience 19, 196
197.
2009 Blackwell Publishing

Mendhekar D.N., Sunder K.R. & Andrade C. (2006) Aripiprazole

use in a pregnant schizoaffective woman. Bipolar disorders 8,
299300.
Mendhekar D.N., War L., Sharma J.B., et al. (2002) Olanzapine
and pregnancy. Pharmacopsychiatry 35, 122123.
Misri S., Corral M.R., Wardrop A.A., et al. (2006) Quetiapine
Augmentation in Lactation. Journal of Clinical Psychopharmacology 26, 508511.
Nagy A., Tenyi T., Lenard K., et al. (2001) Olanzapine and pregnancy. Orvosi Hetilap 142, 137138.
Newcomer J.W. (2007) Metabolic considerations in the use of
antipsychotic medications: a review of recent evidence. Journal
of Clinical Psychiatry 1, 2027.
Nguyen H.N. & Lalonde P. (2003) Clozapine and pregnancy.
Encephale 29, 119124.
Nordeng H. & Spigset O. (2003) Use of antipsychotics during
pregnancy and lactation. Tidsskrift for Den Norske laegeforening 123, 20332035.
Oates M. (1989) Management of major mental illness in pregnancy and the puerperium. Baillieres Clinical Obstetrics and
Gynaecology 3, 905920.
Pinkerton J.V., Finnerty J.J., Lombardo P.A., et al. (1997) Parental
rights at the birth of a near-viable infant: conflicting perspectives. American Journal of Obstetrics and Gynecology 177,
283288. Discussion 288290.
Pinkofsky H.B. (1997) Psychosis during pregnancy: treatment
considerations. Annals of Clinical Psychiatry 9, 175179.
Pinkofsky H.B. (2000) Effects of antipsychotics on the unborn
child: what is known and how should this influence prescribing?
Paediatric Drugs 2, 8390.
Potts M., Prata N., Walsh J., et al. (2006) Parachute approach to
evidence based medicine. British Medical Journal 333, 701
703.
Sacker A., Done D.J. & Crow T.J. (1996) Obstetric complications
in children born to parents with schizophrenia: a meta-analysis
of case-control studies. Psychological Medicine 26, 279
287.
Seeman M.V. (2004) Relational ethics: when mothers suffer
from psychosis. Archives of Womens Mental Health 7, 201
210.
Talbot N.L., Conwell Y., OHara M.W., et al. (2005) Interpersonal psychotherapy for depressed women with sexual abuse
histories: a pilot study in a community mental health center.
Journal of Nervous and Mental Disease 193, 847850.
Taylor T.M., OToole M.S., Ohlsen R., et al. (2003) Safety of
Quetiapine during pregnancy. The American Journal of Psychiatry 160, 588589.
Tenyi T., Trixler M. & Keresztes Z. (2002) Quetiapine and pregnancy. The American Journal of Psychiatry 159, 674.
Trixler M. & Tenyi T. (1997) Antipsychotic use in pregnancy.
Drug Safety 16, 403410.
Trixler M., Gati A., Fekete S., et al. (2005) Use of antipsychotics
in the management of schizophrenia during pregnancy. Drugs
65, 11931206.
Usher K. & Foster K. (2006) The use of psychotropic medications
with breastfeeding women: applying the evidence. Contemporary Nurse 21, 94102.
Usher K., Foster K. & McNamara P. (2005) Antipsychotic drugs
and pregnant or breastfeeding women: the issues for mental
health nurses. Journal of Psychiatric and Mental Health
Nursing 12, 713718.

103

K. McCauley-Elsom et al.

Yaegar D., Smith H.G. & Altshuler L.L. (2006) Atypical antipsychotics in the treatment of schizophrenia during pregnancy and
the postpartum. American Journal of Psychiatry 163, 2064
2070.
Yaris F., Yaris E., Kadioglu M., et al. (2004) Use of polypharmacotherapy in pregnancy: a prospective outcome in a case.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 28, 603605.
Yogev Y., Ben-Haroush A. & Kaplan B. (2002) Maternal
clozapine treatment and decreased fetal heart rate variability.

104

International Journal of Gynaecology and Obstetrics 79, 259

260.
Yoshida K., Kumar R.C., Smith B., et al. (1998a) Psychotropic
drugs in breast milk: no evidence for adverse effects on prepulse
modulation of startle reflex or on cognitive level in infants.
Developmental Psychobiology 32, 249256.
Yoshida K., Smith B., Craggs M., et al. (1998b) Neuroleptic drugs
in breast-milk: a study of pharmacokinetics and of possible
adverse effects in breast-fed infants. Psychological Medicine 28,
8191.

2009 Blackwell Publishing