ArticlePDF AvailableLiterature Review

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. MethodsA 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. ResultsThe 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.
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.
4
Due 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
studies
5-8
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 al
10
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. Einarson
11
and Einarson
& Boskovic
12
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 al
13
found an increased risk
of prematurity and low birth weight in infants
exposed to haloperidol or penfluridol during
pregnancy. Newham et al
14
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 al
15
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 al
17
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 al
18
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 al
23
, found rates of
miscarriage (13%) to be in the normal range.
Einarson et al
12
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 al
26
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 al
14
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 al
14
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 al
25
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
J Popul Ther Clin Pharmacol Vol 19(3):e380-e386; October 11, 2012
© 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 al
26
found a 10%
risk of low birthweight babies in those exposed to
second generation antipsychotics as opposed to
2% in unexposed women. Newport et al
31
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.
17
Antidepressants 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.
4
Withdrawal 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 milk
35
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.
e385
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.
... Therefore, women with schizophrenia require proper psychiatric care and counseling with regard to pregnancy and family planning. Once pregnant, their care involves comprehensive interventions including personal and social support and pharmacotherapy (Robinson, 2012). ...
... Therefore, any such safety concerns must be weighed against the risks of stopping medications before making a decision. Discontinuation of antipsychotics particularly, abrupt discontinuation, may lead to relapse (Robinson, 2012;Taylor et al., 2015). Similarly, this mother had defaulted treatment which contributed to a relapse during her pregnancy. ...
Article
Full-text available
Child abuse is a widely discussed issue that can have a lasting negative imprint on a child’s life. We report a case of castration in an infant of nine months old, perpetrated by the mother, who was a diagnosed with schizophrenia. This case explores a rare form of physical child abuse (PCA) and it also emphasizes the need of a program in the healthcare system to monitor mentally challenged mothers throughout the pregnancy and afterward.
... Most women are diagnosed with BD and SZ between 18 and 30 years old and between 25 and 35 years old, respectively, which overlaps with childbearing years (Kessler et al., 2005). Pregnancy and, in particular, the postpartum period are characterized by elevated relapse in women diagnosed with BD and SZ (Edinoff et al., 2022;Jones et al., 2014;McNeil et al., 1984;Robinson, 2012;Rusner et al., 2016;Viguera et al., 2011). Unfortunately, it remains poorly understood. ...
Article
Full-text available
Prevalence of mental disorders, including major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ) are increasing at alarming rates in our societies. Growing evidence points toward major sex differences in these conditions, and high rates of treatment resistance support the need to consider novel biological mechanisms outside of neuronal function to gain mechanistic insights that could lead to innovative therapies. Blood-brain barrier alterations have been reported in MDD, BD and SZ. Here, we provide an overview of sex-specific immune, endocrine, vascular and transcriptional-mediated changes that could affect neurovascular integrity and possibly contribute to the pathogenesis of mental disorders. We also identify pitfalls in current literature and highlight promising vascular biomarkers. Better understanding of how these adaptations can contribute to mental health status is essential not only in the context of MDD, BD and SZ but also cardiovascular diseases and stroke which are associated with higher prevalence of these conditions.
... The majority of antipsychotic medications used to treat schizophrenia appear to be relatively safe for use during breastfeeding. 23 Antipsychotic drugs are excreted in breast milk, but to date breast fed infants have not shown signs of toxicity or impaired development in most reports of antipsychotics, although manufacturers advise avoidance of these drugs during breast feeding. There are few reports on prescribing antipsychotic medication while breast feeding. ...
Article
Full-text available
Breastfeeding is the optimal feeding mode for the mother and her child. The pregnancy rates of mothers with schizophrenia do not differ significantly from those of the general population. However, research on breastfeeding among women with schizophrenia is extremely limited. The current study aims to explore the health professionals' attitudes towards breastfeeding among women with schizophrenia in Greece and to examine the validity and reliability of the Greek version of a specific rating scale for further research on attitudes towards breastfeeding among women with schizo-phrenia. This study had a cross-sectional descriptive design and the participants were health professionals working closely with women/mothers at different health care settings in Athens (health visitors, midwives , nurses working in mental health care). Data were collected using a self-report questionnaire on knowledge and attitudes regarding breastfeeding, knowledge, feelings and attitudes regarding schizo-phrenia, professional guidance for women with schizophrenia about breastfeeding; and personal and professional attitudes towards breastfeeding among women with schizophrenia. The results of the study showed that health care professionals of different disciplines seemed to have similar positive attitudes towards breastfeeding among women with schizophrenia. Professionals that had attended breastfeed-ing seminars had significantly greater scores on both knowledge of breastfeeding and attitudes towards breastfeeding. Greater scores on attitudes towards women with schizophrenia and attitudes towards breastfeeding among women with schizophrenia were found in those that had previous contact with a person with schizophrenia. Furthermore, greater scores on attitudes towards women with schizophrenia were found in those that have provided consultation to a woman with schizophrenia on breastfeeding issues. The results suggest that this tool is a reliable and valid measure. The results of the exploratory factor analysis showed that there was a discriminative capacity among items. The five derived factors were knowledge of breastfeeding, attitudes towards breastfeeding, knowledge of schizophrenia, attitudes towards women with schizophrenia, attitudes towards breastfeeding among women with schizophrenia. Further research is needed among medical doctors and other mental health professionals who are involved in the care of women with schizophrenia. In addition, the experiences and the needs of mothers with schizophrenia should be explored in order to gain useful information for practice. The results of the current and future studies are expected to inform strategic planning.
... Nevertheless, it is still necessary to make treatment recommendations based on the accumulated current information. It is generally accepted that there is a greater risk for the mother and the fetus in not treating schizophrenia during pregnancy and postpartum than in providing antipsychotic treatment (48). ...
Article
Full-text available
The involvement of gonadal hormones in the pathogenesis of schizophrenia has long been suspected because the psychosis differs in women and men and the illness first makes its appearance shortly after puberty. Changes in sex hormones have been linked with increased vulnerability to mood disorders in women, while testosterone have been associated with increased sexual drive and aggressiveness in men as well as women. Some studies have found abnormal levels of estrogens and testosterone in schizophrenia patients, but the results have been inconsistent and sometimes attributed to the hyperprolactinemia effect of antipsychotics, which may interfere with sex hormones production. The purpose of this review is to present the current knowledge on the link between blood levels of sex-hormones in women during the various stages of the female reproductive life (i.e. puberty, menstrual cycle, pregnancy, contraception, and menopause) and the course of schizophrenia. We also attempt to optimize the clinical approach to women with schizophrenia at these different stages.
... 8 Although fertility rates are generally lower in patients with schizophrenia than in healthy individuals of the same age, 9 the fertility rate is increasing, 10,11 reflected by the growing number of pregnancies in women taking atypical antipsychotics. 12 Safety data on the use of the other atypical antipsychotics quetiapine, olanzapine, and aripiprazole during pregnancy do not suggest that their use is associated with a clinically meaningful increased risk of congenital malformation. 13 However, there are few data on the risk of using clozapine during pregnancy. ...
Article
Full-text available
Purpose Safety data on clozapine use during pregnancy are limited. The aim of this study was to determine disproportionality in case safety reports on adverse pregnancy outcomes between clozapine and other antipsychotics (OAP) used during pregnancy. Methods We included all reports of suspected adverse drug reactions (ADRs) to antipsychotics registered in the World Health Organization global individual case safety report (ICSR) database (VigiBase) in children younger than 2 years and women aged 12‐45 years. A case/non‐case approach was used to evaluate the association between several pregnancy‐related ADRs and clozapine exposure during pregnancy, using 2×2 contingency tables to investigate disproportionality and Standard MedDRA Queries to select cases. Clozapine exposure was defined as all ICSR‐ADR combinations with clozapine as (one of) the suspected drug(s). Non‐exposure was defined as all ICSR‐ADR combinations with OAP as (one of) the suspected drug(s). Results We identified 42 236 unique ICSR‐ADR combinations related with clozapine exposure and 170 710 with OAP exposure. Of these, 494 and 4645 ICSR‐ADR combinations involved adverse pregnancy outcomes related with clozapine exposure and OAP exposure respectively. Overall, no signal of disproportionate reporting associating clozapine with the studied adverse pregnancy outcomes was found compared with OAP exposure. Conclusion Based on global pharmacovigilance data, we did not find any evidence that clozapine is less safe during pregnancy than OAP. Although this is not automatically equivalent to the relative safety of clozapine during pregnancy, these findings add to the convergence of proofs to allow final conclusions and decisions regarding the treatment of pregnant women with clozapine.
... [5,6] Exposure to psychotropic drugs, exacerbation of schizophrenia, and limited treatment options for schizophrenia in pregnancy and postpartum period complicate the obstetric care and illness outcome of women with schizophrenia. [7,8] Gender-related roles pose specific challenges for married women. Increased rates of coerced and unprotected sex, unwanted and unplanned pregnancies, induced abortions, and difficulties in utilising antenatal health services are some of them. ...
Article
Full-text available
Background: Women with schizophrenia have needs beyond their mental health needs, such as those arising out of their gender, sexual, and reproductive functions. Very little is known about the knowledge, attitude, and practice regarding contraception among women with schizophrenia from India. Materials and methods: Study among women with schizophrenia (in reproductive age group, having at least one living child, and currently staying with husband) from south India explored their knowledge, attitude, and practice of contraception. Adhering to observational design and ethical principles, data were collected using a semi-structured questionnaire. Modified National Family Health Survey-3 questionnaire and Positive and Negative Symptom Scale of Schizophrenia were also used. Results: Ninety-six women with schizophrenia participated. The mean age was 33.5 years [standard deviation (SD): 6.8 years], and the mean age of onset of schizophrenia was 29.2 years (SD: 6.2 years). Although nearly 90% had knowledge on at least one method of contraception, the mean total number of methods known was mere two. Out of 65 women who were practising contraception, 86.2% adopted female sterilization. The common reasons for not using contraception were wish for another child/son, lack of awareness, and fear of side effects. Unmet need for family planning was 14%. Informed choice of contraception was below 3%. There was statistically significant association between those who were currently using contraception and variables such as age 31 years and above, undifferentiated subtype of schizophrenia, and greater severity of schizophrenia. Conclusion: Although the majority had some knowledge about contraception, decision-making largely rested with others, and informed choice regarding contraception was poor. These could pose an obstetric risk on women with schizophrenia. Sociocultural and illness-related factors influencing contraception need to be explored.
Article
Active peripartum psychiatric illness is associated with adverse outcomes for exposed pregnancies/children. Likely due to high rates of obesity, pregnant women with psychiatric illness also have higher rates of preeclampsia, cesarean section, and gestational diabetes. Postpartum depression is associated with lower IQ, slower language development, and behavioral problems in exposed children. Discontinuing psychiatric medications for pregnancy increases risk for relapse significantly, and the postpartum time period is high risk for developing psychiatric illness. Obstetricians-gynecologists are front-line providers for psychiatric care of women during peripartum. This article provides a framework and knowledge base for management of psychiatric illness during peripartum.
Article
Background and Objective Quetiapine and aripiprazole are currently prescribed for pregnant women to treat schizophrenia and bipolar disorder. A dramlatic decline in the plasma concentrations of these two drugs was observed if the doses remained fixed throughout pregnancy. This study aims to develop physiologically based pharmacokinetic (PBPK) models to predict the pharmacokinetics of quetiapine, aripiprazole, and the active aripiprazole metabolite dehydroaripiprazole during pregnancy.Methods We developed models using a combined ‘bottom-up’ and ‘top-down’ strategy. Models were verified by assessing goodness-of-fit plots and ratios of predicted-to-observed pharmacokinetic parameters. To extrapolate to pregnancy, we considered anatomical, physiological, and metabolic alterations. The in silico models were applied to predict steady-state pharmacokinetics in the three stages of pregnancy and to inform dose selection.ResultsWe successfully constructed PBPK models that accurately predicted the pharmacokinetics of drugs in the adult population. Predictions suggested that the area under the concentration–time curve at steady state in the first, second, and third trimesters, respectively, decreased by 8.7%, 35.0%, and 49.1% for quetiapine and 12.6%, 38.8%, and 60.9% for the active moiety of aripiprazole. The third-trimester plasma concentrations of quetiapine were below the lower limit of the therapeutic range (100 ng/mL) for most of the time interval, and aripiprazole was entirely unable to reach its effective concentration (150 ng/mL).Conclusions According to PBPK predictions, the doses should be increased in the latter two trimesters. We generally recommend that women during late pregnancy take at least 2.5- and 2-times their baseline doses of quetiapine and aripiprazole, respectively.
Chapter
Psychiatric illness during and immediately after pregnancy is common and potentially life-threatening. The proper management of psychiatric disorders during the peripartum time period remains controversial, though this is likely secondary to the stigma associated with psychiatric illness rather than a lack of data. Much of the early literature exploring the relationship between in utero psychiatric medication exposure and infant outcomes was flawed by inappropriate control populations, small sample sizes, and a lack of controls for confounds including psychiatric illness itself and associated health risk factors and behaviors. More recent studies are generally better designed to study whether infant outcomes are influenced by in utero medication exposure or by exposure to maternal psychiatric illness or both. The preponderance of the literature is reassuring regarding the safety of the use of most (not all) psychiatric medications during pregnancy and lactation. The preponderance of the literature also supports that unfavorable infant outcomes are associated with exposure to maternal mental illness. This chapter attempts to summarize what is currently known about the safety of psychiatric medications during pregnancy and lactation and, in addition, describes a clinical approach to designing a treatment plan for individual patients during this critical time for both mother and child.
Article
Full-text available
We sought to evaluate the capacity of the Edinburgh Postnatal Depression Scale (EPDS) in discriminating mental disorders other than depression in pregnant women in northern Mexico. Three hundred pregnant women attending prenatal consultations in a public hospital in Durango City, Mexico submitted a validated EPDS and were examined for mental disorders other than depression using the Diagnostic and Statistical Manual of Mental Disorders - 4th Ed. (DSM-IV) criteria. Sensitivity and specificity of cut-off points of the EPDS, and positive and negative predictive values were calculated. Of the 300 pregnant women studied, 21 had mental disorders other than depression by the DSM-IV criteria. The best EPDS score for screening mental disorders other than depression was 8/9. This threshold showed a sensitivity of 52.4%, a specificity of 67.0%, a positive predictive value of 11.5%, a negative predictive value of 95.4%, and an area under the curve of 0.643 (95% confidence interval: 0.52-0.76). The EPDS can be considered for screening mental disorders other than depression in Mexican pregnant women whenever a cut-off score of 8/9 is used. However, the tool showed small power to separate pregnant women with and without mental disorders other than depression.
Chapter
An important issue in the maintenance treatment of schizophrenia is the rate of relapse upon discontinuation of therapy. This chapter discusses the time course of schizophrenic patients relapsing while on placebo and illustrates the data taken from several large collaborative studies and the related mathematical analyses in that matter. If a patient does not relapse after a long period of time, one might assume that the patient will never relapse. In an attempt to clarify this point, Hogarty and co-workers (1976) followed their placebo group for 2 or more years after the initial study. They found that almost all patients had relapsed or were lost to follow-up. Indeed, after 18 months, the empirical data hinted that the relapse rate was decreasing, but so few patients remained that the placebo group did not yield a sufficient number of unrelapsed patients for accurate study. The role of maintenance medication for a single episode of reactive psychosis has not been studied. It is reasonable to use short-term treatment for 6 months or so to ensure a solid recovery without necessarily resorting to long-term maintenance. The length of the therapy should be determined based on the knowledge of the illness as well as the patient's life situation. Reactive schizophrenic patients can have one episode and never relapse, and in these cases, a long-term maintenance medication may not be necessary. Whether maintenance therapy is needed for a patient after a first episode remains a clinical judgment.
Article
Background: A substantial number of women of childbearing age suffer from schizophrenia and other mental illnesses that require the use of antipsychotic drugs. Atypical antipsychotics have been on the market since the mid-1990s, and to date there are no prospective comparative studies regarding use during pregnancy. Objectives: (1) To determine whether atypical antipsychotics increase the rate of major rnalformations above the 1% to 3% baseline risk seen in the general population. (2) To examine rates of spontaneous and therapeutic abortions, rates of stillbirths, birth weight, and gestational age at birth. Method: The cohort was composed of pregnant women who contacted the Motherisk Program in Canada or the Israeli Teratogen Information Service in Israel and women who were recruited from the Drug Safety Research Unit database in England. Women who had been exposed to atypical antipsychotics were matched to a comparison group of pregnant women who had not been exposed to these agents. Results: Data were obtained on 151 pregnancy outcomes that included exposure to olanzapine (N = 60), risperidone (N = 49), quetiapine (N = 36), and clozapine (N = 6). Among women exposed to an atypical antipsychotic, there were 110 live births (72.8%), 22 spontaneous abortions (14.5%), 15 therapeutic abortions (9.9%), and 4 stillbirths (2.6%). Among babies of women in this group, there was 1 major malformation (0.9%), and the mean +/- SD birth weight was 3341 685 g. There were no statistically significant differences in any of the pregnancy outcomes of interest between the exposed and comparison groups, with the exceptions of the rate of low birth weight, which was 10% in exposed babies compared with 2% in the comparison group (p = .05), and the rate of therapeutic abortions (p = .003). Conclusion: These results Suggest that atypical antipsychotics do not appear to be associated with an increased risk for major malformations.
Article
Objective: To comprehensively and critically review the literature on gender differences in schizophrenia. Method: An initial search of MEDLINE abstracts (1966-1999) was conducted using the terms sex or gender and schizophrenia, followed by systematic search of all relevant articles. Results: Males have consistently an earlier onset, poorer premorbid functioning and different premorbid behavioral predictors. Males show more negative symptoms and cognitive deficits, with greater structural brain and neurophysiological abnormalities. Females display more affective symptoms, auditory hallucinations and persecutory delusions with more rapid and greater responsivity to antipsychotics in the premenopausal period but increased side effects. Course of illness is more favorable in females in the short- and middle-term, with less smoking and substance abuse. Families of males are more critical, and expressed emotion has a greater negative impact on males. There are no clear sex differences in family history, obstetric complications, minor physical anomalies and neurological soft signs. Conclusion: This review supports the presence of significant differences between schizophrenic males and females arising from the interplay of sex hormones, neurodevelopmental and psychosocial sex differences.
Article
Psychiatric illness can occur during pregnancy and the postpartum period. Not only will the mother feel distressed but also these illnesses can cause direct and indirect harm to the baby as well as create long-term negative consequences for the mother and the couple. Although using medication during pregnancy or breastfeeding may worry some patients and physicians, untreated depression, anxiety, or psychoses may cause even more harm. Research on the effects of psychotropic drugs on the fetus and on breastfeeding is limited by the inability to establish gold standard trials. Research that is published must also be viewed critically because poor methodologies can lead to unwarranted and alarming conclusions. To date, available information suggests that most antidepressants do not cause major clinical malformations but do cause a slightly elevated risk of miscarriage and preterm delivery. Typical antipsychotics also appear to be relatively safe to use during pregnancy. Less information is available about atypical antipsychotics, but no specific patterns of harm have been detected. Valproic acid has a high risk of causing malformations. Most psychotropic medications are compatible with breastfeeding. The clinician must use the evidence available to make risk/benefit analyses about the best course of action. Educating the mother about what information is available assists her in making decisions that will be of most benefit to her and her baby.
Article
The risks and benefits of psychopharmacological treatment in pregnancy need careful consideration. Conventional antipsychotics and tricyclic antidepressants are relatively safe for the foetus. Selective serotonin reuptake inhibitors appear to be safe, but mood stabilisers such as lithium, sodium valproate and carbamazepine are associated with increased foetal malformations. Benzodiazepines in the first trimester are teratogenic, and in high dosage can also cause withdrawal symptoms, hypotonia and agitation in the newborn. Women taking atypical antipsychotics should be switched to conventional antipsychotics before they conceive. In women with long-term mental illness necessitating psychotropic medication, effort should be made to stop polypharmacy and non-essential medication (e.g. benzodiazepines) and to decrease the dose of essential drugs, after full assessment. There is rarely a valid reason to stop essential drug treatment during pregnancy.
Article
— Postpartum psychotic episodes (PPPs) occurring during the first 6 months after delivery were prospectively studied in 88 pregnant index women with a history of nonorganic psychosis and 104 pregnant controls with no such history. While no control developed a PPP, PPPs were found following 28% of the index deliveries, almost all of these 25 cases being psychiatrically hospitalized. PPPs were especially frequent among cases with total illness diagnoses of Cycloid Psychosis and Affective Illness. More than half of the 25 cases had symptom onset within 3 weeks of delivery, and these early onset cases represented predominantly affective disorders, many of whom were manic in this episode. Cases with onset after 3 weeks were predominantly schizophrenic. Confusion was part of the current episode symptomatology in about one third of the cases and was well distributed across the different diagnostic groups.