REVIEW

CURRENT
OPINION Psychopharmacological treatment of schizophrenia
during pregnancy and lactation
Alexandra B. Whitworth

Purpose of review
It is necessary, in every-day clinical life when treating pregnant women with mental diseases, to reach
quick decisions derived from recent comprehensive information. The knowledge of the use of antipsychotics
in pregnancy has increased considerably in the last years. This review tries to summarize important
considerations and facilitate clinical decisions.
Recent findings
This review will cover not only the effects of exposure during pregnancy on outcomes, postnatal adaption
syndrome and lactation, but also pharmacokinetic considerations on the use of antipsychotics during
pregnancy.
Summary
The recent publications have found only minimally increased risks for certain malformations, after using
ever more sophisticated statistical models of analysis and reassuring amounts of data. Taken together, the
quality of the studies has greatly improved and the results are reassuring with respect to the safety of the
use of antipsychotics during pregnancy. The rates of weight gain and gestational diabetes warrant closer
attention in the clinical setting.
Keywords
antipsychotics, pregnancy, schizophrenia, treatment

INTRODUCTION SCHIZOPHRENIA AND PARENTHOOD

This review was undertaken as there are hardly
ever enough data on this sensitive, rapidly chang-
ing topic for clinicians to arrive at the best
decisions for mother and baby. As treating phys-
icians/psychiatrists, we have to be continuously
aware of the reproductive safety of psychiatric
medication at every clinical step and with every
decision.
It is also not sufficient to recommend a first-line
treatment. We need information about all available
substances, because pregnant women come into our
offices with all kinds of substances and combi-
nations. With respect to schizophrenia, women
mostly fall ill before pregnancy and not always with
a compatibility of their medication with a preg-
nancy in mind. There is a general agreement
between all authors that there is a greater risk for
mother and baby outcomes in not treating schizo-
phrenia during pregnancy.
A Pub Med search was performed covering the
last 18 months – we slightly extended the publi-
cation period to include relevant articles.
Pregnancies occur in 50% of women with
schizophrenia – not always intended [1]. With
the introduction of second-generation antipsy-
chotics (SGAs) and their increasing use, the unin-
tentional contraceptive effect of first-generation
antipsychotics (FGAs) caused by hyperprolactine-
mia is fading. This explains the rise of the general
fertility rate among women with schizophrenia by
1.16 times over the past 13 years [2]. A population-
based study from the United States [3] found a
2.5-fold increase in the use of SGAs in pregnancy
during the study period, whereas FGAs remained at
a stable level. Diagnosis included depression in
63%, followed by bipolar disorder (43%) and schizo-
phrenia (13%). Over the study period, a shift of
diagnostic patterns from schizophrenia to bipolar
Correspondence to Alexandra B. Whitworth, Hellbrunnerstraße, 11a,
5020 Salzburg, Austria. Tel: +43 699 17093233;
e-mail: mypsychiaterin@aon.at
Curr Opin Psychiatry 2017, 30:184–190
DOI:10.1097/YCO.0000000000000329

www.co-psychiatry.com Volume 30  Number 3  May 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Antipsychotic treatment during pregnancy should be
limited to severe mental disorders not
manageable otherwise.
 Drug dose should be split into several doses over the
day and adapted to changes in drug metabolism
during pregnancy and according to plasma levels,
taking the prepregnancy, efficacious levels as an
orientation.
 Regular comprehensive medical check-ups are
necessary.
 Delivery should be planned in hospitals with a
neonatologist available, preferably with neonatal
intensive care units.
 Close follow-ups of the newborn and mother by a
multiprofessional team are highly recommended.
disorder was noteworthy – most likely depicting
changed indications and prescribing patterns.
An earlier review [4] found available data too
limited to draw definite conclusions on structural
teratogenicity of FGAs and SGAs. Another group [5]
could not find any clear evidence for a risk for
malformations, but identified other risks associated
with pregnancy and neonatal outcomes, such as
gestational diabetes, prematurity and high or low
birth weight.
ORIGINAL ARTICLES
Cohort and registry studies
Taken together, recent studies give an increasingly
clearer picture: A couple of studies with slightly
increased rates of malformations are noticeable
& & && && &
(see Table 1) [6,7,8 ,9,10 ,11 ,12 ,13,14 ].
&
The worldwide WHO registry study [10 ]
showed an increased signal for gastrointestinal mal-
formations for phenothiazines with piperazine side-
chains as well as for risperidone and aripiprazole.
The authors discuss that their results are not con-
trolled for possible confounders and can therefore
only be considered as safety signals. A small
&&
increased risk for risperidone was found [12 ] and
a review of 12 studies [15] also reported an increased
relative risk (RR) for malformations of 1.5 for risper-
idone and 1.4 for aripiprazole. In contrast, the preg-
nancies of 713 women exposed to risperidone,
evaluated in an older study [16], did not result in
an excess of malformations compared with the gen-
eral population. A study of aripiprazole in 86 preg-
nancies did not find any significant malformation
&
risk [8 ]. These results suggest that a malformation
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Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Treatment of schizophrenia during pregnancy Whitworth
risk, if present, is not likely to be very high, but
should be explored in further, more specific studies.
Two hundred and fourteen women using SGAs
and 89 comparison women were followed prospec-
tively [13]. The absolute risk for major malfor-
mations was 1.4% for exposed and 1.1% for not-
exposed-to-SGAs infants, but the authors argue that
after a sensitivity analysis and an adjustment of
potential confounding factors, the true value of
the risk could be closer to 1 for the exposed group.
In a prospective cohort study of 147 pregnancies
exposed to SGAs, 22% instances of gestational dia-
betes and 6% malformations were found – without a
clear pattern or adjustment for confounding factors
[9].
After adjustment for confounding health and
&& && &
lifestyle factors, several large studies [11 ,12 ,14 ]
indicated no increased risk for maternal or perinatal
negative outcomes such as gestational diabetes,
hypertensive disorder or preterm birth and birth
&&
weight, only [12 ] and reported a slightly elevated
risk for risperidone only for overall (RR 1.26) and
cardiac malformations (RR 1.26).
&&
In a matched cohort analysis [11 ], the risk for
the neonatal adaptive syndrome was reduced to a
small, nonsignificant relative risk.
Finally, data were gathered about clozapine use
during pregnancy and compared with risperidone,
olanzapine and quetiapine. Signs for delayed devel-
opment of the infants exposed to clozapine at 2 and
6 months were found – with the neurodevelopmen-
tal differences disappearing at 12 months [7]. In the
absence of longer term studies, clinicians should be
advised to limit the use of clozapine to clearly treat-
ment-resistant, severely ill patients.
CASE REPORTS
More recently introduced antipsychotics such as
paliperidone are the topic of case reports. Two such
reports, covering the exposure to paliperidone
throughout pregnancy, reported good tolerance
and no malformations. Both infants were followed
up after 4 months [17] and 1 year [18] and showed
appropriate development for their age.
Another case [19] describes a reduction of fetal
heart rate variability during exposure to clozapine
with the phenomenon spontaneously dissolving
toward the end of the pregnancy.
After a suicide attempt during pregnancy with
an unknown amount of quetiapine at gestational
week 37, the mother delivered a healthy newborn by
cesarean section [20].
A pregnant women with psychotic disorder
developed life-threatening ketoacidosis after taking
20 mg/day of olanzapine for 10 weeks up to week 31
www.co-psychiatry.com 185
Schizophrenia and related disorders

Table 1. Pregnancy and antipsychotics

Study Study design Numbers and antipsychotic Outcome

Sorensen et al. [6] Historical cohort study n ¼ 2000 pregnancies No " risk of spontaneous abortion in the same
exposed to AP woman comparing exposed with
unexposed pregnancy
n ¼ 1 005 319 Danish Two-fold " risk for stillbirth
registries as controls
Shao et al. [7] Posthoc analysis n ¼ 33 pregnancies At 2 and 6 months, adaptive behavior scores
exposed to clozapine significantly lower in infants exposed to
clozapine
n ¼ 30 exposed to risperidone, At 12 months, differences had dissolved
olanzapine and quetiapine
Bellet et al. [8 ] Prospective cohort study n ¼ 86 exposed to aripiprazole " rates of prematurity and fetal growth
&

Kulkarni et al. [9]
Montastruc et al. [10 ]
&
Prospective cohort study
WHO registry study from
retardation on aripiprazole
n ¼ 172 unexposed
n ¼ 147 pregnancies 22% gestational diabetes
exposed to APs
6% congenital malformations without specific
patterns
n ¼ 9 286 170 reports " signals of disproportionate reporting for

1967 to 2014 gastrointestinal tract congenital disorders

(palate, esophageal and anorectal)
n ¼ 351,028 exposed to APs FGAs>SGA, especially phenothiazines with a
piperazine side-chain and risperidone, to a
lesser extent aripiprazole
Vigod et al. [11 ] High-dimensional, n ¼ 1021 pregnancies Minimal impact of AP on maternal medical
&&

propensity matched, exposed to AP and perinatal outcome

population-based cohort
study
n ¼ 1021 matched controls
Huybrechts Cohort study, propensity n ¼ 9258 SGA No increased risk for congenital
et al. [12 ] score stratification malformations, only small increase for
&&

Cohen et al. [13]
Petersen et al. [14 ]
&
Prospective cohort study
Cohort study
risperidone
n ¼ 733 FGA prescription filled
during first trimester
n ¼ 214 SGA Unadjusted OR for major malformations
comparing exposed with unexposed infants:
1.25
n ¼ 89 controls not exposed to
SGAs
n ¼ 416 APs during pregnancy Only very limited risks for adverse pregnancy

and birth outcomes after adjustments for

lifestyle and health factors
n ¼ 670 APs discontinued before
pregnancy
n ¼ 318,434 no AP before or
during pregnancy

aOR, adjusted odds ratio; AP, antipsychotic; FGA, first-generation antipsychotic; OR, odds ratio; SGA, second-generation antipsychotic.

of gestation. The authors speculate that this was due REVIEWS

to olanzapine in combination with a possible insu-
lin resistance [21].
A triplet pregnancy exposed to clozapine was
monitored. One of the three male babies had macro-
cephaly at birth, but all were developed normally by
the age of 20 months [22].
A review and meta-analysis evaluated obstetric and
neonatal outcomes after antipsychotic exposure and
covered 13 cohort studies comparing 1 618 039
unexposed to 6289 exposed pregnancies [23]. There
was limited adjustment for possible confounders
and the authors conclude that the increased risk

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of major malformations [odds ratio (OR) 2.12] and
heart defects (OR 2.09) did not necessarily imply
causation, but necessitates close monitoring and
minimization of other risk factors, such as smoking,
weight gain, substance use, medical comorbidities
or psychosocial stressors.
Reviewing the exposure to SGAs in the first
trimester in original data, another group [15] calcu-
lated relative risk estimates for congenital malfor-
mations of 1.0 for olanzapine (n ¼ 1090), 1.0 for
quetiapine (n ¼ 443), 1.5 for risperidone (n ¼ 432)
and 1.4 for aripiprazole (n ¼ 100) compared with
nonexposed pregnancies.
&
A large review and meta-analysis [24 ] compar-
ing 1782 cases with 1 322 749 controls reported an
increased risk for major congenital malformations
(OR 2.03) with SGA use during the first trimester,
but a specific pattern of malformations could not
be detected.
A review of 21 studies [25] examined clozapine
exposures during pregnancy and lactation with
the majority stemming from case reports and
series. The authors conclude that although con-
genital malformations have been reported, they do
not seem to exceed the rate in the general popu-
lation, but rates of gestational diabetes were twice
as high compared with mothers not taking anti-
psychotics.
&&
In a comprehensive clinical synopsis [26 ],
intended as a guideline for daily practice, olanza-
pine, risperidone, quetiapine and – in treatment-
resistant cases – clozapine are recommended, if
antipsychotics are to be prescribed during preg-
nancy.
An overview of psychotropic drug management
&&
during pregnancy [27 ] with different levels of
recommendations based on the amount of evidence
for safety provided by animal and human studies
incorporates the former FDA drug-labeling
categories and uses a color code. The new FDA rule
‘Pregnancy and Lactation Labelling Rule’ will be
phased in over the next years.
CHANGES OF DRUG METABOLISM AND
DOSING DURING PREGNANCY
It is important to be aware of several changes in
metabolism and drug clearance during pregnancy
&
[28 ,29]. These include increasing (CYP2D6,
CYP2C9 and CYP3A4) or decreasing (CYP1A2 and
CYP2C19) enzyme activities as well as increases of
renal blood flow and glomerular filtration rate.
Given the interindividual variability of pharmaco-
genetic properties (of mother and fetus), monthly
therapeutic drug monitoring (TDM) of trough drug
levels is indicated to allow for the lowest possible
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Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Treatment of schizophrenia during pregnancy Whitworth
dose, adapting to different stages of metabolism and
pregnancy as well as clinical symptoms.
In the absence of large-scale studies on the
course of antipsychotic plasma levels during preg-
nancy, dose adjustments should target plasma levels
that were efficacious before pregnancy.
Especially clozapine and olanzapine, both pref-
erentially metabolized by CYP1A2, and therefore
likely to show increasing plasma levels during preg-
nancy, call for TDM to prevent intoxication or
serious adverse events in mother and fetus. Other
antipsychotics such as risperidone, quetiapine and
aripiprazole are mainly metabolized by CYP2D6 and
3A4, enzymes with increased activity during preg-
nancy resulting in a decrease of plasma levels,
especially in the third trimester, as demonstrated
in a case series covering three pregnancies exposed
to aripiprazole [30].
POSTNATAL ADAPTATION SYNDROME
After exposure to psychotropic drugs during
pregnancy, infants are at risk of developing symp-
toms of poor neonatal adaptation (PNA). The
symptoms mostly occur within 48 h after birth
and can last 2–6 days. They are characterized by
agitation, jitteriness, tremors, abnormal muscle
tone, sleeping and feeding difficulties and respir-
atory distress.
A case report [31] describes PNA following
exposure to quetiapine and lamotrigine. The new-
born suffered a shoulder dystokia and needed mask
ventilation with Apgar scores 0 at 1 min, 3 at 5 min
and 3 at 10 min. He developed severe irritability and
feeding difficulties, and was successfully treated
with phenobarbitone.
A review has [32] attempted to further define the
syndrome. On the one hand, symptoms can be
interpreted as withdrawal after abrupt delivery-
related drug discontinuation developing after
several hours and persisting even though exposure
has stopped. On the other hand, drug toxicity is a
possible explanation – with symptoms occurring
directly after birth. Another, more recent review
[33] also dichotomizes neonatal adaptation issues
into withdrawal syndromes and residual pharmaco-
logical effects. The exposure to FGAs and SGAs
seems to be associated with PNA rates ranging from
15 to 27%.
This topic has not been well studied and
described in the context of antipsychotic exposure
– exact numbers and descriptions are not available.
The same applies for risk factors such as premature
birth. The possible occurrence of such compli-
cations makes delivery at a hospital with a neonatal
intensive care unit advisable.
www.co-psychiatry.com 187
Schizophrenia and related disorders
NEURODEVELOPMENT OF INFANTS
EXPOSED TO ANTIPSYCHOTICS IN UTERO
This topic was reviewed [34] and included only
original data and a follow-up period of the infants
of at least 4 months. The authors conclude that
the question whether in utero exposure to anti-
psychotics negatively affects brain development
remains unresolved.
A recent large observational study [35] com-
pared neurodevelopment at 9 and 24 months of
493 children exposed to various psychotropic drugs
(anxiolytics, antidepressants, neuroleptics and epi-
leptics) during the second and/or third trimester to
32.303 nonexposed children. Increased risk for
abnormal motor development was found in exposed
children – it was not possible to adjust for con-
founding factors or distinguish between groups
of substances.
In conclusion, long-term neurodevelopmental
outcome after exposure to antipsychotics during
pregnancy remains unclear and warrants further
study.
LACTATION
The exposure through breastfeeding differs con-
siderably compared to that during pregnancy, as
only small amounts of the drug are secreted into
breast milk. In a comprehensive clinical overview,
the relative infant dose (RID), a quantitative esti-
mate of the amount of drugs passing from mother to
infant via breast milk, is between 0 and 2% for most
of the antipsychotics, and side-effects in breastfed
&&
infants are only rarely described [26 ]. An RID
below 10% is considered compatible with breast-
feeding. Olanzapine, quetiapine and aripiprazole
can be used; ziprasidone and paliperidone are not
recommended, because of insufficient data. Risper-
idone, with an RID between 3 and 9%, and cloza-
pine – due to the side-effect profile – are not
recommended. FGAs and breastfeeding are mostly
not recommended because of insufficient data. Most
data seem to exist for the use of olanzapine and the
drug was frequently below the level of detection in
the infant’s plasma [36].
CONCLUSION
Several questions about confounding factors such as
course and severity of the disease during pregnancy
remain unanswered. The influence of chronic stress
from a severe mental disease was demonstrated to
result in small-for-gestational-age babies and pre-
term deliveries by depressed mothers without medi-
&&
cation [37 ].
188 www.co-psychiatry.com
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
The same is likely relevant regarding the
exposure to antipsychotics – as seen in several
& &&
studies and reviews [9,10 ,11 ].
Psychotic mothers are probably not less prone to
chronic stress than mothers with an affective dis-
order. Maternal psychiatric disease and epigenetic
phenomena are suggested as an underlying mech-
anism for poor fetal growth [38].
Weight or weight increase during pregnancy
and their connection to gestational diabetes and
malformation risks have also to be kept in mind
as confounding factors [39,40].
Smoking, alcohol and other drugs of abuse,
socioeconomic status and lifestyle factors also have
an effect on pregnancy outcomes in women with
schizophrenia. Investigators try hard to eliminate
the influence of such confounding factors. Com-
parison groups may be large, but they mostly consist
of healthy women or women with other psychiatric
disease disorders – not untreated women with
schizophrenia and comparable characteristics of dis-
ease, substance use, lifestyle and stress factors.
Electronic health records provide large numbers,
but only a limited picture of the clinical status
and real-life situations. It is therefore important to
create and use techniques to minimize confounding
influences such as the high-dimensional propensity
&& &&
score [11 ] or a propensity score stratification [12 ]
and to gather more information on patient charac-
teristics.
All of these topics and many more are addressed
in an excellent review of clinical interventions for
pregnant women with schizophrenia [41], empha-
sizing the necessity for a comprehensive approach.
This should start with the sexual history and one of
intimate relationships, as well as information on a
possible intent for pregnancy and the use of birth
control methods in all our female patients of child-
bearing age. If patients do become pregnant, they
should be connected to prenatal and postnatal care
services and support systems, as well as engaged in a
multidisciplinary management for the treatment of
their mental disorder.
To be able to treat mother and baby in an
optimal way, a concise evaluation of diagnosis
and treatment before conception– including evi-
dence of efficacy of every drug ever taken, length
and severity of relapses, time since last episode and
family history in the context of childbirth is necess-
ary.
This preconceptional management should limit
medication recommendations to the ‘absolutely
necessary level’ with monotherapy and the lowest
possible dose in mind. Ideally, this should also
include the plasma level-based therapeutic drug
monitoring.
Volume 30  Number 3  May 2017

All evidence taken together, there appears to be
a minimal risk for babies of mothers with schizo-
phrenia exposed to antipsychotics during preg-
nancy for different outcomes and lower risks
being reported for olanzapine and quetiapine [15].
Given the methodological differences between
studies and complexities of the underlying disease,
it is currently not possible to reliably quantify these
risks or to clearly attribute effects and draw generally
applicable conclusions. Obviously, this calls for a
case-by-case decision process, closely involving the
mother and a multiprofessional team, as well as
always carefully evaluating the benefit/risk ratio
when considering the use of psychotropic drugs
during pregnancy and keeping mother and baby
well over this important stage of life.
Acknowledgements
I much appreciate the editorial advice of Professor W.
Wolfgang Fleischhacker.
My manuscript includes unlabeled/investigational uses
of antipsychotics during pregnancy, which is an off-label
use.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. McGrath JJ, Hearle J, Jenner L, et al. The fertility and fecundity of patients with
psychoses. Acta Psychiatr Scand 1999; 99:441–446.
2. Vigod SN, Seemann MV, Ray JG, et al. Temporal trends in general and age-
specific fertility rates among women with schizophrenia (1996-2009): a popu-
lation-based study in Ontario. Canada Schizophr Res 2012; 139:169–175.
3. Toh S, Li Q, Cheetham TC, et al. Prevalence and trends in the use of
antipsychotic medications during pregnancy in the U.S., 2001–2007: a
population-based study of 585 615 deliveries. Arch Womens Ment Health
2013; 16:149–157.
4. Gentile S. Antipsychotic therapy during early and late pregnancy. A systema-
tic review. Schizophrenia Bull 2010; 36:518–544.
5. Galbally M, Snellen M, Power J. Antipsychotic drugs in pregnancy: a review of
their maternal and fetal effects. Ther Adv Drug Saf 2014; 5:100–109.
6. Sorensen MJ, Kjaersgaard M, Sondergaard H, et al. Risk of fetal death after
treatment with antipsychotic medications during pregnancy. Plos One 2015;
7:e0132280.
7. Shao P, Ou J, Peng M, et al. Effects of clozapine and other atypical
antipsychotics on infants development who were exposed to as fetus: a
posthoc analysis. Plos One 2015; 10:e123373.
8. Bellet F, Beyens M, Bernard N, et al. Exposure to aripiprazole during
& embryogenesis: a prospective multicenter cohort study. Pharmacoepidemiol
Drug Saf 2015; 24:368–380.
This is the first prospective study looking at aripiprazole during pregnancy.
9. Kulkarni J, Storch A, Baraniuk A, et al. Antipsychotic use in pregnancy. Expert
Opin Pharmacother 2015; 16:1335–1345.
10. Montastruc F, Salvo F, Arnaud M, et al. Signal of gastrointestinal congenital
& malformations with antipsychotics after minimising competition bias: a dispro-
portionality analysis using data from Vigibase. Drug Saf 2016; 39:689–696.
A worldwide, large registry study finding a specific malformation pattern for certain
antipsychotics – considering them as ‘safety signals’ as confounders could not be
controlled for.
0951-7367 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Treatment of schizophrenia during pregnancy Whitworth
11. Vigod S, Gomes T, Wilton A, et al. Antipsychotic drug use in pregnancy: high
&& dimensional, propensity matched, population based cohort study. BMJ 2015;
350:h2298.
Very sophisticated technique to minimize confounding and by matching showing
that none of the negative pregnancy outcomes was associated with the use of
antipsychotics.
12. Huybrechts KF, Hernandez-Diaz S, Patorno E, et al. Antipsychotic use in
&& pregnancy and the risk of congenital malformations. JAMA Psychiatry 2016;
73:938–946.
Another matched cohort study of a large Medicaid database using propensity
scores to separate malformation rates from the effects of the underlying
psychiatric disease. After application, the RR was near the null for SGAs
and FGAs for general and cardiac malformations with the exception of
risperidone.
13. Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-
generation antipsychotics: current data from the Massachusetts General
Hospital National Pregnancy Registry for atypical antipsychotics. Am J
Psychiatr 2016; 173:263–270.
14. Peterson I, Sammon JS, McCrea RL, et al. Risks associated with antipsychotic
& treatment in pregnancy: comparative cohort studies based on electronic
health records. Schizophrenia Res 2016; 176:349–356.
Large study adjusting for health, lifestyle and concomitant medication finding no
significant differences.
15. Ennis ZN, Damkier P. Pregnancy exposure to olanzapine, quetiapine, risper-
idone, aripiprazole and risk of congenital malformations. A systematic review.
Basic Clin Pharmacol Toxicol 2015; 116:315–320.
16. Coppola D, Russo LJ, Kwarta RF Jr, et al. Evaluating the postmarketing
experience of risperidone use during pregnancy: pregnancy and neonatal
outcomes. Drug Saf 2007; 30:247–264.
17. Özdemir AK, Pak SC, Canan F, et al. Paliperidone palmitate use in pregnancy
in a woman with schizophrenia. Arch Womens Ment Health 2015; 18:739–
740.
18. Zamora-Rodriguez FJ, Benitez Vega C, Sanchez-Waisen Hernandez MR, et al.
The use of paliperidone palmitate throughout a schizoaffective disorder
patient’s gestation period. Pharmacopsychiatry 2017; 50:38–40.
19. Guyon L, Auffret M, Coussemacq M, et al. Alteration of the fetal heart rate
pattern induced by the use of clozapine during pregnancy. Thèrapie 2015;
70:301–303.
20. Paulzen M, Gründer G, Orlikowsky T, et al. Suizide attempt during late
pregnancy with quetiapine: nonfatal outcome despite severe intoxication.
J Clin Psychophramacol 2015; 35:343–344.
21. Frise C, Attwood B, Watkinson P, Mackillop L. Life-threatening ketoacidosis
in a pregnant woman with psychotic disorder. Obstetr Med 2016; 9:
46–49.
22. Sreeraj VS, Venkatasubramanian G. Safety of clozapine in a woman with
triplet pregnancy: a case report. Asian J Psychiatr 2016; 22:67–68.
23. Coughlin CG, Blackwell KA, Bartley C, et al. Obstetric and neonatal outcome
after antipsychotic medication exposure in pregnancy. Obstet Gynecol 2015;
125:1224–1235.
24. Terrana N, Koren G, Pivovarov J, et al. Pregnancy following in utero exposure
& to second-generation antipsychotics. A systematic review and meta-analysis.
J Clin Psychopharmacol 2015; 35:559–565.
Increased risk for malformations, but unable to separate underlying disease from
effects of SGAs.
25. Metha T, Van Lieshout RJ. A review of the safety of clozapine during
pregnancy and lactation. Arch Womens Ment Health 2017; 20:1–9.
26. Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs
&& during pregnancy and breast-feeding. Acta Psychiatr Scand 2015; 132
(Suppl 445):1–28.
Comprehensive review for the clinician’s daily use.
27. Chisholm MS, Payne JL. Management of psychotropic drugs during preg-
&& nancy. BMJ 2015; 351:h5918.
Also, very useful covering a wide range of psychotropic drugs using a color code to
enable quick decisions.
28. Pariente G, Leibson T, Carls A, et al. Pregnancy-associated changes in
& pharmacokinetics: a systematic review. PLoS Med 2016; 13:e1002160.
Useful overview.
29. Pavek P, Ceckova M, Staud F. Variation of drug kinetics in pregnancy. Curr
Drug Metab 2009; 10:520–529.
30. Windhager E, Sung-Wan K, Saria A, et al. Perinatal use of aripiprazole, plasma
levels, placental transfer, and child outcome in 3 new cases. J Clin Psycho-
pharmacol 2014; 34:637–641.
31. Lau C, Watson H, Cheong J. Poor neonatal adaptation following
in-utero exposure to quetiapin and lamotrigine. J Obstet Gynaecol 2015;
35:646.
32. Kieviet N, Dolman KM, Honig A. The use of psychotropic medication during
pregnancy: how about the newborn? Neuropsychiatric Dis Treat 2013;
9:1257–1266.
33. Convertino I, Sansone AC, Marino A, et al. Neonatal adaptation after maternal
exposure to prescription drugs: withdrawal syndromes and residual pharma-
cological effects. Drug Saf 2016; 39:903–924.
34. Gentile S, Fusco ML. Neurodevelopmental outcomes in infants exposed in
utero to antipsychotics: a systematic review of published data. CNS Spectr
2016; 21:1–9.
www.co-psychiatry.com 189
Schizophrenia and related disorders
35. Hurault-Delarue C, Damase-Michel C, Finotto L, et al. Psychomotor devel-
opmental effects of prenatal exposure to psychotropic drugs: a study in
EFEMERIS database. Fundam Clin Pharmacol 2016; 30:476–482.
36. Uguz F. Second-generation antipsychotics during the lactation period: a
comparative systematic review on infant safety. J Clin Psychopharmacol
2016; 36:244–252.
37. Malm H, Sourander A, Gissler M, et al. Pregnancy complications following pre-
&& natal exposure to SSRI or maternal psychiatric disorders: results from popula-
tion-based National Register Data. Am J Psychiatr 2015; 172:1224–1232.
Proving chronic stress in depressed mothers as a confounding factor for low birth
weight.
190 www.co-psychiatry.com
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
38. Ciesielski TH, Marsit CJ, Williams SM. Maternal psychiatric disease and
epigenetic evidence suggest a common biology for poor fetal growth. BMC
Pregnancy Childbirth 2015; 15:192.
39. Gentile S. Pregnancy exposure to second generation antipsychotics
and the risk of gestational diabetes. Expert Opin Drug Saf 2014; 13:
1583–1590.
40. Carmichael SL, Rasmussen SA, Shaw GM. Prepregnancy obesity: a complex
risk factor for selected birth defects. Birth Defects Res A Clin Mol Teratol
2010; 88:804–810.
41. Seeman MV. Clinical interventions for women with schizophrenia: pregnancy.
Acta Psychiatr Scand 2013; 127:12–22.
Volume 30  Number 3  May 2017