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J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e380
TREATMENT OF SCHIZOPHRENIA IN PREGNANCY AND POSTPARTUM
Gail Erlick Robinson
University of Toronto and University Health Network, Toronto, Ontario, Canada
Corresponding Author: gail.robinson@utoronto.ca
Symposium Proceedings Motherisk Update 2012, Toronto, Canada
ABSTRACT
Background
The prime age of onset for schizophrenia in women is during the childbearing years from ages 25-35. 50-
60% of these women will become pregnant; fifty percent of these pregnancies will be unplanned or
unwanted. Discontinuation of medication will likely lead to a relapse of the illness during pregnancy or
postpartum. Although research on the safety of psychotropic medication during pregnancy and
breastfeeding is limited, it is still necessary to make treatment recommendations based on the
accumulated information of the best available studies.
Objectives
To give an overview of what is known about the risks/benefits of antipsychotic medications during
pregnancy and postpartum and make treatment recommendations for pregnant schizophrenic women.
Methods
A review was done on Pubmed, Medline and Cochrane to locate any studies or articles addressing the
safety and efficacy of antipsychotic medication use in pregnancy and during breastfeeding and treatment
planning for pregnant schizophrenic women.
Results
The majority of antipsychotic medications used to treat schizophrenia appear to be relatively safe for use
during pregnancy and breastfeeding.
Conclusions
There appears to be greater risk for the mother and the fetus/infant in not treating schizophrenia during
pregnancy and postpartum. Recommendations are made about the treatment of schizophrenic women in
order to achieve the best outcome for mother and baby.
Key Words: Schizophrenia, pregnancy, breastfeeding, antipsychotic medication
The prime onset for schizophrenia in women is
during the childbearing years from ages 25-35.1
Fertility may be reduced in schizophrenic women,
partly related to the illness itself and partly as a
side effect of typical antipsychotic medications.2,3
Currently, with better care and increased use
of atypical (second generation) antipsychotics, 50-
60% will become pregnant; fifty percent of these
pregnancies will be unplanned or unwanted as
women with chronic schizophrenia may be poor at
family planning and are at high risk of being
sexually assaulted. These women are more likely
to be unmarried and have fewer social supports.
As such, they are at greater risk of being deemed
incompetent to mother and having the added
burden of having to give up their children. Good
preventative health care of schizophrenic women
with the potential to become pregnant should,
Treatment of schizophrenia in pregnancy and postpartum
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e381
therefore, begin with attention to contraception
use with the aim of avoiding unwanted
pregnancies.
For those women who choose to become
pregnant or wish to keep their pregnancies, care
involves comprehensive intervention including
personal and social supports and
psychopharmacology. Assessing the effects of
psychotropic drugs during pregnancy is not an
easy task.4Due to ethical issues, no studies of
medication during pregnancy meet the gold
standard of randomized, placebo-controlled,
double-blind, crossover trials. Few studies control
for age of the patient, previous pregnancy loss,
dosages, timing of administration, multiple drug
use or substance abuse. Many studies base their
findings on the fact that the women were given a
prescription for a medication without proving that
the patient has actually taken it.
Given the limitations of the research, it is still
necessary to make recommendations based on the
accumulated information of the best available
studies on the safety of antipsychotic medication
during pregnancy or breastfeeding. In evaluating
any negative effects of taking medication during
pregnancy concerns include: whether there is an
increased risk of miscarriage; the risks of major
malformations in the baby; any problems during
labour; difficulties for the neonate; safety during
breastfeeding: and the occurrence of long-term
problems in the child. In determining whether a
drug is teratogenic, the defect must either have a
distinctive pattern (such as the limb problems that
occurred with thalidomide) or occur at a rate
greater than 3%, the general rate of defects found
in newborns.
Any of these concerns must be weighed
against the risks of stopping medication during
pregnancy. Discontinuation of medication, will
likely lead to illness relapse. Reviews of relevant
studies5-8 have concluded that, over follow-up
periods of up to 2 years, relapse of illness in those
patients who have withdrawn from antipsychotics
occurs in around 50%, while for people who have
continued on medication it is about 15%. In other
words, for those patients stopping antipsychotic
medication the risk of relapse is 2–3 times greater
than it would have been if they had stayed on it,
and the risk of relapse is greater with abrupt
discontinuation compared with a gradual
withdrawal.
Schizophrenia has been associated with
multiple obstetrical complications including low
APGAR scores, prematurity, low birth weights,
small for gestational age babies, stillbirth and
death.2,9 It is unclear whether these outcomes are
due to the illness itself or problems that might
occur during the pregnancy. Women with
schizophrenia may fail to attend prenatal
appointments, eat poorly, smoke more and abuse
alcohol or illegal drugs. Therefore, discontinuing
medication in pregnant schizophrenic women
increases the risk to the fetus and the mother.
ANTIPSYCHOTICS
Typical
Teratogenesis
Although a meta-analysis by Altshuler et al10
found a rate of congenital malformations of 2-
2.4% infants exposed to typical antipsychotics,
there was no specific pattern of abnormality and
the rates detected were below the normal 3% rate
in the general population. Einarson11 and Einarson
& Boskovic12 summarized the findings of multiple
studies and found no increase in teratogenesis in
women taking piperidyl phenothiazines
(thioridizine), piperazines (fluphenazine,
perphenazine), phenothiazines (chlorpromazine,
promethazine), piperazine phenothiazines
(trifluoperazine), butyrophenones (haloperidol),
thioxanthenes (flupenthixol), dibenzoxazepines or
diphenylbutylpiperidines.
Labour and Delivery
It is difficult to differentiate between the effects of
the medications versus the effects of the illness
itself. Diav-Citrin et al13 found an increased risk
of prematurity and low birth weight in infants
exposed to haloperidol or penfluridol during
pregnancy. Newham et al14 found that those
exposed to typical antipsychotics during
pregnancy had a significantly lower mean birth
weight and a higher incidence of small for
gestational age infants than the reference group.
However, Lin et al15 concluded that the risks for
low birth weight and small for gestational age
babies among women with schizophrenia did not
differ regardless of exposure to antipsychotics
Treatment of schizophrenia in pregnancy and postpartum
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e382
although there was an increased risk of preterm
birth (OR=2.46), after adjusting for potential
confounders.
Effects on the Neonate
Some typical antipsychotics such as
chlorpromazine, flupenthixol and fluphenazine
have been associated with a risk of neonatal
withdrawal and extrapyramidal signs that may last
for weeks to months.16 The use of promethazine in
late pregnancy could induce respiratory distress in
the newborn and impaired platelet aggregation in
the mother and the newborn.11 Kohen et al17 has
described a rare syndrome in the neonate
consisting of respiratory distress, difficulty
feeding, floppy infant syndrome, hypertonicity,
sluggish primitive reflexes, extrapyramidal
symptoms, tremor, abnormal movements,
irritability and agitation which generally resolve
within days.
Johnson et al18 reported that infants exposed
to antipsychotic drugs during pregnancy
demonstrated 10% poorer motor skills at 6
months. Their findings were limited to 22 cases of
which 20 were also taking antidepressants,
anxiolytics and/or hypnotics. The motor skills
scores were significantly associated with the
maternal psychiatric history. It was also not clear
whether or not these effects were transient.
Long-Term Effects
Intelligence quotients at age four were not found
to be different in children exposed to
antipsychotics during the first four months of
pregnancy as compared to children of controls.19
No differences have been found in behavior,
socialization or cognition in nine and ten year olds
who were exposed to chlorpromazine in utero.20,21
ATYPICAL
Miscarriage
There are two case reports of pregnancy loss due
to high neural tube defects in women taking
aripiprazole.22 In 23 cases of women taking
olanzapine, Goldstein et al23, found rates of
miscarriage (13%) to be in the normal range.
Einarson et al12 reported an 8.8% risk of
miscarriage in 57 reported cases of women talking
ziprasidone.
Teratogenesis
Although limited information is available on
clozapine, olanzapine, quetiapine and risperidone,
there is no conclusive evidence of an increased
risk of teratogenesis.24,25 In a prospective
comparative study of 110 pregnant women on
atypical antipsychotics no increased risk or
specific patterns of major congenital
malformations were detected.26 Aripiprazole,
ziprasidone and paliperidone (a metabolite of
risperidone) are the newest atypical
antipsychotics. Only a few case reports have been
published but none of these have shown any
excess in specific malformations.
There may, however, be an indirect risk; the
use of atypicals during pregnancy may lead to
weight gain that, in turn, can increase the risk for
neural tube defects, hypertension, pre-eclampsia
and gestational diabetes.27,28 Pregnancy can impair
glucose tolerance from the second trimester
onwards, and several cases of gestational diabetes
associated with the use of clozapine, olanzapine
and other atypical antipsychotics during that time
have been reported.29,30
Labour and Delivery
A prospective study by McKenna et al26
concluded that exposure to atypical antipsychotics
during pregnancy did not cause an increased risk
for adverse pregnancy outcomes. Schizophrenia
itself has been associated with an increased risk of
placental abruption, preterm delivery, low birth
weight, stillbirth and neonatal death.
Effects on the Neonate
Newham et al14 found that infants exposed to
atypical antipsychotics had a significantly higher
incidence of large for gestational age (LGA)
babies than both comparison groups and a mean
birth weight significantly heavier than those
exposed to typical antipsychotics. Newham et al14
found that infants exposed to atypicals had a
significantly higher risk of being large for
gestational age than either controls or infants
whose mothers had taken typical antipsychotics.
Yaeger et al25 have also described an increased
risk of hypoglycaemia and macrosomia resulting
in shoulder dystocia and associated birth injuries
such as fractures and nerve palsies. The weight
gain and possible gestational diabetes induced by
Treatment of schizophrenia in pregnancy and postpartum
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© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e383
atypicals increase the risk of macrosomia,
hypoglycemia, shoulder dystocia and associated
birth injuries.24
In contrast, McKenna et al26 found a 10%
risk of low birthweight babies in those exposed to
second generation antipsychotics as opposed to
2% in unexposed women. Newport et al31 found
tendencies toward higher rates of low birth weight
and neonatal intensive care admissions in infants
exposed to olanzapine.
Long-Term Effects
Normal development has been reported in the
offspring of women taking atypical antipsychotics
in pregnancy who have been followed for lengths
of time ranging from six months to five years.24
OTHER MEDICATIONS
There are a variety of other medications that may
be used in the treatment of schizophrenics.
Anticholinergics have been little researched but
may be teratogenic and are best avoided in
pregnancy.17Antidepressants may cause a small
increase in miscarriage risk but do not appear to
cause an increase in major malformations. There
is some risk of the infant experiencing a neonatal
syndrome that tends to be short-lived with no
permanent negative consequences.4
Information on the effects of minor
tranquillizers ranges from some case reports to a
few prospective studies. No increases in
malformations have been reported with
lorazepam, clonazepam, alprazolam, triazolam or
flurazopam.4Withdrawal syndromes may be seen
after use of clonazepam, alprazolam, and
lorazepam. Lorazepam used in late pregnancy
may lead to respiratory distress, decreased
APGARS, problems with temperature regulation
and poor feeding.32 No malformations or delivery
problems have been reported with zopiclone use
but low birth weight, preterm deliveries and small
for gestational age babies have been found after
the use of zopildem.33
POSTPARTUM
The risk for relapse in women with schizophrenia
during the first three months postpartum is
approximately 24%.34 Women who become
psychotic during this time present a possible
danger to themselves or their infants due to
delusional ideation, disorganization or lack of
responsiveness to the infant. This may interfere
with bonding or present a risk to the infant either
due to direct physical harm or neglect.
The main concern about taking medication in
the postpartum is the possible effect on the
breastfeeding infant. Typical antipsychotics are
excreted in breast milk at the rate of less than 3%
of maternal levels.35 Although there have been
some reports of drowsiness and lethargy, the
majority of the reports have not found any adverse
events.11 Less than 5% of atypical antipsychotics
are found in breast milk35 and no negative effects
on the infants have been reported for the majority
of the atypicals. Clozapine has been associated
with sedation, decreased sucking reflex,
restlessness and irritability, seizures and cardiac
instability in the breastfed infant.36
PRINCIPLES OF TREATMENT
Prior to Pregnancy
If a woman with schizophrenia is planning a
pregnancy her psychiatric history and response to
treatment should be carefully reviewed in order to
evaluate the risk of discontinuing medication. If
the woman has been stable for many years on very
small doses of an antipsychotic medication it
might be possible to discontinue it however,
generally, it may be more risky to discontinue
than to continue medications. A discussion should
be held with her (ideally with her partner) about
her personal risk if the medication is discontinued,
the limitations of the research and the current
evidence concerning the safety of antipsychotics
in pregnancy. This discussion should be
documented in the chart.
If the woman decides to stop her medication,
a schedule for gradual discontinuation should be
drawn up and she should be followed very closely
during the pregnancy. Supporting persons should
be enlisted to watch for any early signs of
decompensation.
If the woman who agrees to continue
medication is taking an antipsychotic with a
propensity to increase prolactin secretion, the
plasma prolactin level should be measured. If
significantly increased, this may interfere with
Treatment of schizophrenia in pregnancy and postpartum
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e384
fertility and changing medication should be
considered.
Less is known about the safety of atypical
versus typical antipsychotics. As well, if the
woman has elevated risk factors for type 2
diabetes mellitus, atypical antipsychotics are best
avoided. However, if the atypical antipsychotic
being used is the only medication that stabilizes
the patient, it is safer to maintain this medication
and watch for possible side effects during
pregnancy. In the case of clozapine, concerns
about the potential for relapse usually outweigh
any concerns about its dysglycaemic effect.9
Similarly, if a woman has been taking depot
antipsychotic medication it should be continued if
the risk of recurrence is high.
During Pregnancy
The therapist should first consider whether
psychological interventions such as some type of
psychotherapy would be effective. There is,
unfortunately a dearth of good studies to
document the effectiveness of psychotherapy to
treat psychiatric illness during pregnancy.37 As
with any pregnancy, women with schizophrenia
should take prenatal vitamins plus a daily
supplement of 5mg folate to decrease the risk of
neural tube defects.
If the patient continues to take antipsychotic
medication, prescribe it in the lowest effective
dose and give in divided doses. Dosages often
need to be increased later in pregnancy as there
are further changes in weight, metabolism,
excretion and lean/fat ratios.38 The patient should
avoid diuretics and low-salt diets. Polypharmacy
should be avoided. If the woman is taking an
atypical antipsychotic, regular screening for
gestational diabetes is essential and attempts
should be made to avoid excessive weight gain.
Depot antipsychotic medication should not be
initiated in pregnancy because of the lack of
flexibility in dosing.
Regular follow-up is essential, both to assess
physical well-being and watch for any signs of
deterioration in her mental health. Pre-natal
classes are important to help prepare for
childbirth. Preliminary assessment of capacity to
care for a newborn should begin. Parenting classes
could start for those who capacity is questionable.
Support systems for after the baby is born should
be established.
The psychiatrist should work closely with the
obstetrician to ensure that the patient is not
advised to discontinue medication and proper
monitoring is done during the pregnancy.
In late pregnancy, ultrasound monitoring of
women who have been taking atypical
antipsychotics can determine fetal size and
determine whether vaginal delivery is advisable.
Post-Delivery
The paediatrician or neonatologist should be
alerted to the fact the woman has been taking
antipsychotic medication. If the mother was
taking typical antipsychotics during pregnancy,
the newborn should be monitored for
extrapyramidal side effects for several days. The
occurrence of a neonatal syndrome should be
treated symptomatically. If the mother was taking
clozapine, the infant’s neutrophil count should be
checked.
Postpartum
Schizophrenic women may need lots of support
during the postpartum period. Close follow-up is
required to watch for any return of psychotic
symptoms or inattention to the infant which may
put it at risk. As there is a high risk of
decompensation and return of schizophrenic
symptoms postpartum, medication should be
continued or re-introduced. If the woman requires
admission, ideally it should be in a mother-baby
unit in which she can continue to care for her
baby.
Assessment of their competency to care for
the newborn should be carried out. Children’s
services may be required to offer support to the
mother. Parenting classes may be required to help
the woman be attentive to their infant’s needs.
Breastfeeding is possible while taking
antipsychotics. Mothers may assume that, to be
perfectly safe, they should avoid taking
medication until they finish breastfeeding. Once
again, it is important to clarify with them the
possible risks of not treating a major psychiatric
illness during this time. These include: poor infant
care; rejection of the infant; poor parental
relationships; suicide; infanticide; long term
Treatment of schizophrenia in pregnancy and postpartum
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
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failure to bond with the child; guilt; delayed infant
development; and failure to thrive.
All the antipsychotic medications pass into
breast milk but in levels much lower than in the
mother. Drug excretion into the breast milk of less
than 10% of the maternal dose is unlikely to lead
to dose-related adverse events in the infant.39
Monitor the baby for alertness. Avoid
polypharmacy and use the lowest effective dose. It
is best to avoid breastfeeding when taking
clozapine.
SUMMARY
Although fertility used to be low for
schizophrenic women, current multimodal
treatment is allowing more women to become
pregnant. Discontinuing medication during
pregnancy can cause deterioration in the mother’s
mental health which can increase risks of poor
prenatal care, placental abruption, preterm
delivery, low birth weight, stillbirth and neonatal
death. Attention to contraception can protect
women against unwanted pregnancy. For those
who choose to pursue a pregnancy, knowledge
about the risk/benefits of medication and
provision of adequate psychosocial supports both
during pregnancy and postpartum can promote the
best outcome for mother and child.
REFERENCES
1. Leung A, Chue P. Sex differences in
schizophrenia, a review of the literature. Acta
Psychiatr Scand 2000(Suppl);401:3-38.
2. Howard LM. Fertility and pregnancy in women
with psychotic disorders. Eur J Obstet Gynecol
Reprod Biol 2005;119:3-10.
3. Jarskog LE, Mattioli MA, Perkins DO, et al.
First-episode psychosis in a managed care
setting: clinical management and research. Am J
Psychiatry 2000;157:878-884.
4. Robinson GE. Psychopharmacology in
pregnancy and postpartum. Focus 2012;10(1);3-
14.
5. Barnes TRE and the Schizophrenia Consensus
Group of the British Association for
Psychopharmacology. Evidence-based
guidelines for the pharmacological treatment of
schizophrenia: recommendations from the
British Association for Psychopharmacology. J
Psychopharmacol 2011;25:67-620.
6. Davis JM, Janicak PG, Singla A, Sharma RP.
Maintenance antipsychotic medication. In:
Barnes TRE, ed. Antipsychotic Drugs and Their
Side-Effects New York: Academic Press,
1993:183-203.
7. Gilbert PL, Harris MJ, McAdams LA, Jeste DV.
Neuroleptic withdrawal in schizophrenic
patients. A review of the literature. Arch Gen
Psychiatry 1995;52:173-188.
8. Viguera AC, Baldessarini RJ, Hegarty JD, van
Kammen DP, Tohen M. Clinical risk following
abrupt and gradual withdrawal of maintenance
neuroleptic treatment. Arch Gen Psychiatry
1997;54:49-55.
9. Nilsson E, Lichtenstein P, Cnattingius S, Murray
RM, Hultman CM. Women with schizophrenia:
pregnancy outcome and infant death among their
offspring. Schizophr Res 2002;58:221-229.
10. Altshuler LL, Cohen L, Szuba MP, Burt Vk,
Gitlin M, Mintz J. Pharmacologic management
of psychiatric illness during pregnancy:
dilemmas and guidelines. Am J Psychiatry
1996;153:592-606.
11. Einarson A. Antipsychotic medication
(safety/risk) during pregnancy and
breastfeeding. Curr Women’s Health Rev
2010:6:34-38.
12. Einarson A, Boskovic R. Use and safety of
antipsychotic drugs during pregnancy. J
Psychiatr Pract 2009;15:183-192.
13. Diav-Citrin O, Shechtman S, Ornoy S, et al.
Safety of haloperidol and penfluridol in
pregnancy: a multicentre, prospective controlled
study. J Clin Psychiatry 2005;66:317-322.
14. Newham JJ, Thomas SH, MacRitchie K,
McElhatton PR, McAllister-Williams RH. Birth
weight of infants after maternal exposure to
typical and atypical antipsychotics: prospective
comparison study. Br J Psychiatry
2008;192:333-337.
15. Lin HC, Chen IJ, Chen YH, Lee HC, Wu FJ.
Maternal schizophrenia and pregnancy outcome:
Does the use of antipsychotics make a
difference? Schizophr Res 2010;116:55-60.
16. Solt I, Ganadry S, Weiner Z. The effect of
meperidine and promethazine on fetal heart rate
indices during the active phase of labor. Isr Med
Assoc J 2002;4:178-180.
17. Kohen D. Psychotropic medication in
pregnancy. Adv Psychiatr Treat 2004;10:59-66.
18. Johnson KC, LaPrairie JL, Brennan PA, Stowe
ZN, Newport J. Prenatal antipsychotic exposure
Treatment of schizophrenia in pregnancy and postpartum
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 2012 Canadian Society of Pharmacology and Therapeutics. All rights reserved.
e386
and neuromotor performance during infancy.
Arch Gen Psychiatry 2012;69:787-794.
19. Slone D, Siskind V, Heinonen OP, Monson RR,
Kaufman DW, Shapiro S. Antenatal exposure to
the phenothiazines in relation to congenital
malformations, perinatal mortality rate, birth
weight, and intelligence quotient score. Am J
Obstet Gynecol 1977;128:486-488.
20. Kris EB. Children of mothers maintained on
pharmacotherapy during pregnancy and
postpartum. Curr Ther Res Clin 1965;7:785-789.
21. Stika L, Elisova K, Honzakova L, et al. Effects
of drug administration in pregnancy on
children’s school behaviour. Pharm Weekbl Sci
1990;12:252-255.
22. Kulkarni J, McCauley-Elsom K, Marston M, et
al. Preliminary findings from the National
Register of Antipsychotic Medications in
Pregnancy. Aust N Z J Psychiatry 2008;42:38-
44.
23. Goldstein DJ, Corbin LA, Fung MC.
Olanzapine-exposed pregnancies and lactation:
early experience. J Clin Psychopharm
2004;20:399-403.
24. McCauley-Elsom K, Gurvich C, Elsom SJ,
Kulkarni J. Antipsychotics in pregnancy. J
Psychiatric Ment Health Nurs 2010;17:97-104.
25. Yaeger D, Smith HG, Altshuler LL. Atypical
antipsychotics in the treatment of schizophrenia
during pregnancy and the postpartum. Am J
Psychiatry 2006;163:2064-2070.
26. McKenna K, Koren G, Tetelbaum M, et al.
Pregnancy outcome of women using atypical
antipsychotic drugs: a prospective comparative
study. J Clin Psychiatry 2005;66:444-449.
27. Anderson JL, Waller DK, Canfield MA, Shaw
GM, Watkins ML, Werler MM. Maternal
obesity, gestational diabetes, and central nervous
system birth defects. Epidemiology 2005;16:87-
92.
28. Menon SJ. Psychotropic medication during
pregnancy and lactation. Arch Gynecol Obstet
2008;277:1-13.
29. Gentile S. Antipsychotic therapy during early
and late pregnancy: A systematic review.
Schizophr Bull 2010;36:518-544.
30. Reis M, Kallen B. Maternal use of
antipsychotics in early pregnancy and delivery
outcome. J Clin Psychopharmacol 2008;28:279-
288.
31. Newport DJ, Calamaras MR, DeVane CL, et al.
Atypical antipsychotic administration during late
pregnancy: placental passage and obstetrical
outcomes. Am J Psychiatry 2007;164:1214-
1220.
32. McElhatton PR. The effects of benzodiazepine
use during pregnancy and lactation. Reprod
Toxicol 1994;8:46-75.
33. Wang LH, Lin HC, Lin CC, Chen YH, Lin HC.
Increased risk of adverse pregnancy outcomes in
women receiving zolpidem during pregnancy.
Clin Pharmacol Ther 2010;88:369-374.
34. Mcneil TF. A prospective study of postpartum
psychoses in a high-risk group, 1. Clinical
characteristics of the current postpartum
episodes. Acta Psychiatr Scand 1986;74:205-
216.
35. Gentile S. Infant safety with antipsychotic
therapy in breast-feeding: a systematic review. J
Clin Psychiatry 2000;69:666-673.
36. Malone K, Papagni K, Ramini S, Keltner NL.
Antidepressants, antipsychotics,
benzodiazepines, and the breastfeeding dyad.
Perspect Psychiatr Care 2004;40:73-85.
37. Dennis CL, Ross LE, Grigoriadis S.
Psychosocial and psychological interventions for
treating antenatal depression (review). The
Cochrane Library. Mississauga, Ontario: John
Wiley & Sons, Ltd; 2010(6).
38. Wisner KL, Perel JM, Wheeler SB. Tricyclic
dose requirements across pregnancy. Am J
Psychiatry 1993;150:1541-1542.
39. American Academy of Pediatrics Committee on
Drugs. The transfer of drugs and other chemicals
into human milk. Pediatrics 1994;93:137-150.
