Document name:
The use of psychotropic
medication in women with mental
disorder who are of child bearing
potential, pregnant, planning to
become pregnant, or breastfeeding
Portfolio
Document type:
Medicines Management
Communication
Staff group to whom it applies:
All prescribers, pharmacy and clinical
staff within the Trust
Distribution:
The whole Trust
How to access:
Intranet
Issue date:
December 2012
Next review:
July 2013
Approved by:
Drug and Therapeutics Sub
Committee
Developed by:
Dr. M.S. Harkin on behalf of the Drug
and Therapeutics Trust Action Group
Director leads:
Medical Director
Contact for advice:
Dr. M.S. Harkin
Associate Specialist in Psychiatry
01422 222804
Med.information @swyt.nhs.uk
01924327619
CONTENTS
Summary ……………………………………………………………………. .. .. 1
1
Introduction .................................................................................. .. 2
2
Prescribing in pregnancy and women of child bearing potential ... .. 3
3
Prescribing psychotropic medicines during pregnancy ................ .. 6
3.1
3.2
3.3
3.4
3.5
3.6
3.7
3.8.
3.9
Antidepressants ........................................................................... .. 6
Antipsychotics .............................................................................. .. 8
Benzodiazepines .......................................................................... 10
Lithium.......................................................................................... 11
Carbamazepine and Lamotrigine ………………………………… 12
Valproate …………………………………………
14
Procyclidine………………………………………………………………15
Propranolol……………………………………………………………….15
Promethazine ……………………………………………………………15
4
4.1
Prescribing during breastfeeding .................................................. .. 16
General principles ........................................................................ .. 16
5
Prescribing psychotropic medicines whilst breastfeeding............. .. 18
5.1
5.2
5.3
5.4
5.5
5.6
5.7
Antidepressants ........................................................................... .. 18
Antipsychotics .............................................................................. .. 21
Benzodiazepines .......................................................................... .. 22
Lithium.......................................................................................... .. 22
Carbamazepine and Lamotrigine ................................................. .. 23
Valproate ...................................................................................... .. 24
Other drugs .................................................................................. .. 24
6
Useful information sources .............................................................. 24
7
Glossary of medical terminology .............................................. .. 25
8
References ................................................................................... .. 28
ii
SUMMARY

No medicines are without risk in pregnancy and breastfeeding.

On the basis of maternal past mental health history, current presentation,
and/or probable/possible risks of relapse, consider:
o Is treatment needed now or likely to be needed later?
o If yes to any of these, research the relevant drug(s) you might want
to consider prescribing, using this document for initial basic
guidance, pharmacy advice and the relevant (more central)
information sources quoted.

Undertake a full and individualised risk-benefit analysis, discuss with the
patient +/- partner/carer/family and document all decisions clearly.

Attempt to use the least harmful (yet most clinically effective) medication(s)
overall, hopefully securing the optimal outcome for mother and child.

Valproate preparations have a high risk of teratogenicity. This must be
considered when prescribing for women of childbearing potential.

Always weigh up the risk-benefit ratio for both mother and infant.
ABBREVIATIONS
BNF
British National Formulary
NTIS
National Teratology Information Service
SIGN
Scottish Intercollegiate Guidelines Network
UKTIS
UK Teratology Information Service
PPHN
persistent pulmonary hypertension of the newborn
FGA
first generation antipsychotic
TCA
tricyclic antidepressant
1
1
INTRODUCTION
Important note: this policy is concerned solely with psychotropic
usage and is not designed to discuss either specific psychiatric
conditions or perinatal care pathways.
1.1
Pregnancy and childbirth carry significant risks with regard to new-onset,
recurrent or pre-existing mental disorder.
To briefly illustrate this point (bearing in mind the above caveat), examples
are given below.
Up to two-thirds of women with bipolar affective disorder experience an
episode post-partum. The risk remains even if a woman has been well for
2 years before and also during the pregnancy.
The risk of post-partum psychosis is 50-90% in previously afflicted
mothers.
Women with a history of depression are at increased risk of a further
episode post-partum (figures vary greatly between studies but can be as
high as 50-80%).
Women with depression who discontinue antidepressants in pregnancy
frequently relapse, with rates as high as 68%.
There is a significant increase in NEW psychiatric episodes in the first 3
months after delivery. At least 80% are mood disorders (usually
depression).
Depression itself during pregnancy or postpartum is also associated with a
range of adverse outcomes for the offspring (including poor infant growth,
sudden infant death, and infant/childhood problems in the cognitive,
emotional and behavioural domains).
In general terms, however, to minimise the risk to the foetus or child,
drugs should be prescribed cautiously for all women who are planning a
pregnancy, pregnant or breastfeeding. The risk of unplanned pregnancy
should also be borne in mind when prescribing in all women of childbearing potential (including those of younger age or of impulsive
temperament).
Ultimately the crucial issue is balancing the risks of using medication for
each woman and her child against those of leaving the actual or potential
mental disorder untreated or inadequately treated.
2
1.2
Practice point : Discuss contraception and the risks of pregnancy
(including relapse, risks associated with stopping or changing medication,
and risks to the foetus) with all women of child-bearing potential who have
a mental disorder and/or who are taking psychotropic medication.
Encourage them to discuss pregnancy plans.
1.3
Potential risks of drugs include:

major malformation (first trimester exposure)

miscarriage (spontaneous abortion)

neonatal toxicity and withdrawal effects (third trimester
exposure)

long-term neurobehavioural effects and growth impairment
1.4


Risks of NOT treating severe mental illness include:
harm to the mother – through poor self-care, self harm, impulsive
acts, poor judgement, misuse of substances (including nicotine,
alcohol and illicit drugs)
harm to the foetus or neonate (ranging from prematurity and low birth
weight to serious consequences such as neglect and infanticide).
1.5
It should be borne in mind that the background risk of foetal malformations
in the general population is 2-3% (between 2 and 3 in 100 pregnant
women without a mental disorder). The risk of malformations is increased
by some psychotropic drugs, but it is often difficult to quantify because of
limited data and the impact of lifestyle factors such as diet, smoking and
alcohol use.
1.6
In general, for a woman with a severe mental illness at high risk of
relapse, abrupt discontinuation of treatment on discovery of the
pregnancy is probably unwise.
Mental state should be monitored if a woman decides to cease her usual
medication.
3
2
PRESCRIBING IN PREGNANCY AND WOMEN OF CHILD-BEARING
POTENTIAL
Utilise non-pharmacological interventions for less severe mental disorders
as appropriate (e.g. counselling, support, cognitive behavioural therapy).
Address the individual woman’s fears, views, wishes and priorities and
assess risks of relapse/deterioration if medication is to be withheld or
discontinued. Also take into account implications for breast feeding.
2.1
Be aware that safety data is very limited (based on a retrospective
database which relies on voluntary contributions) and for some
medications there may be no published data at all. Absence of evidence
of danger does NOT imply evidence of safety.
2.2
Note that published case reports tend to be biased towards adverse
outcomes.
2.3
Obtain the most up to date information and seek advice from specialist
pharmacists, senior colleagues or the UK Teratology Information Service
(telephone 0844 892 0909 Monday – Friday and
www.nyrdc.nhs.uk/Services/teratology/teratology.html).
2.4
Document all discussions and treatment plans (NICE suggest audiotaping
consultations if possible, and providing a copy to the service user) and
bear in mind issues of information governance and risks to confidentiality.
Involve the patient and the carer/partner in all discussions and treatment
planning.
2.5
Provide verbal and written information about medication (including risk
issues), preferably individualised, in a form that is appropriate and
culturally sensitive.
2.6
Useful information is available on the website of the pharmacy department
of the Norfolk and Waverley Mental Health NHS Foundation Trust
(www.nmhct.nhs.uk/pharmacy/drugidx.htm) or
www.choiceandmedication.org.uk
2.7
Describe risks using natural frequencies rather than percentages (i.e. 1 in
10 rather than 10%). Common denominators (e.g. 1 in 100 and 25 in 100
rather than 1 in 100 and 1 in 4) may be useful when discussing
comparative risks.
2.8
When working with adolescents with a mental disorder during pregnancy,
consider confidentiality and the rights of the child. Obtain appropriate
consent with consideration of the adolescent’s understanding, parental
consent and responsibilities, child protection issues and the use of the
Mental Health Act and the Children Act (1989).
4
2.9
Folic acid is recommended in all women planning pregnancy: 400
micrograms (0.4 mg) per day before conception and during the first 12
weeks of pregnancy (or 5 mg if there is a history of neural tube defect in a
previous child).
2.10
Take into account past severe mental illness and response to specific
treatment(s).
Don’t assume that it is always better to stop medication.
Review case notes.
Do not prescribe ‘safer’ options if they have been known to fail in the past.
Be aware that switching drugs MAY increase the risk of relapse.
2.11
Treat with medication when potential benefit outweighs potential harm (to
mother and/or the foetus/child) and consider the (potentially substantial)
risks of failing to treat.
Relapse may ultimately be more harmful to the mother and child than
continued and effective treatment.




try to avoid all medicines in the first trimester (all risks considered)
avoid polypharmacy where possible
use established drugs at the lowest effective dose
If possible avoid drugs that are ‘contraindicated’ during pregnancy
in all women of reproductive age (and this applies especially to
carbamazepine and valproate). Inform women of their teratogenic
properties even if pregnancy is not planned at this stage
2.12
Folic acid prophylaxis (5 mg per day) should be used in all women
receiving carbamazepine or valproate and vitamin K administered to both
mother and neonate post-delivery.
2.13
Ensure appropriate and adequate foetal screening during pregnancy.
2.14
For certain drugs, dose titration and plasma level monitoring may be
required in the third trimester and around the time of delivery due to
potential pharmacokinetic changes.
2.15
Establish links with obstetric staff as regards psychotropic drug use and
potential complications (a written care plan is recommended). The
obstetric team should be provided with a contact number and asked to
inform the mental health team as soon as possible after delivery.
2.16
Monitor the neonate post-partum for adverse effects, toxicity or withdrawal
symptoms (these include floppy baby syndrome, irritability, excessive
crying, shivering, tremor, restlessness, increased muscle tone, seizures,
feeding and sleeping difficulties).
5
3
PRESCRIBING PSYCHOTROPIC MEDICINES DURING PREGNANCY
3.1
Antidepressants
Infants exposed to antidepressants in utero should ideally be delivered in
a unit with neonatal support and the delivery team made aware of the
exposure. The neonate should be monitored for adverse effects for up
to 2 days post-delivery (UKTIS).
Tricyclic antidepressants have been widely used throughout pregnancy
without apparent damage to the foetus, but may increase the risk of preterm delivery and neonatal withdrawal symptoms (mild/self-limiting) if used
in the third trimester.
The Maudsley guidelines suggest the use of nortriptyline, amitriptyline
or imipramine. Remember that these are more dangerous than SSRIs if
taken in overdose.
The BNF suggests the use of amitriptyline only if the potential benefit
outweighs the risk.
UKTIS (2012) reports one case of oesophageal atresia and tracheooesophageal fistula and another of fetal tachyarrhythmia following
maternal use of dosulepin (although the overall rate of congenital
malformations is not significantly increased over the background rate).
SSRIs have been associated with
 decreased gestational age (e.g. fourfold increase in risk of delivery
before 36 weeks (but risks no greater than in untreated depression))
 spontaneous abortion (but no conclusive evidence that SSRIs are the
cause)
 gestational raised blood pressure in late pregnancy
 decreased birth weight
 lower APGAR scores at birth
 withdrawal symptoms in the newborn (up to one third) – generally
resolves within 48 hours
 case reports of anencephaly, craniosynostosis, hypospadias,
omphalocele, undescended testes and gastroschisis (see glossary)
 one reported case of intraventricular heamorrhage in the foetus
following administration of paroxetine throughout pregnancy (UKTIS
2011)
 congenital cardiac malformations (including septal heart defects): the
absolute risk is about doubled from 1 in 100 to 2 in 100 with regard to
both paroxetine and fluoxetine (2010 Drug Safety Update)
 persistent pulmonary hypertension of the newborn, presenting as
severe hypoxaemia (5 cases per 1000 pregnancies c.f. the background
rate of 1-2 per 1000 pregnancies). This applies when SSRIs have
6

been used in late pregnancy (i.e. after 20 weeks’ gestation). All SSRIs
have been implicated. The UK Teratology Service has, in 2011,
recommended that SSRIs should be avoided in late pregnancy unless
the ‘indication is compelling’.
increased perinatal complications including respiratory distress and
admissions to intensive care
The BNF indicates that manufacturers advise that SSRIs should not be
used during pregnancy unless the potential benefit outweighs the risk.
Neonatal withdrawal symptoms are mentioned with regard to fluoxetine
and paroxetine.
SNRIs:
The Maudsley guidelines indicate that venlafaxine does not yet appear to
be teratogenic (limited data) but babies may be born small for gestational
age.
The BNF advises avoiding the use of venlafaxine unless potential benefit
outweighs the risk and it draws attention to the risk of withdrawal effects in
the neonate. It mentions that toxicity has been seen in animal studies.
According to UKTIS (2011), limited data (as yet) regarding venlafaxine
show no increased rate of congenital malformations. The possible
associations with spontaneous abortion and pre-term delivery are as yet
unproven. The development of PPHN is currently theoretical. Neonatal
problems include: respiratory problems, convulsions, hypoglycaemia and
low APGAR score.
The BNF advises that duloxetine is associated with toxicity in animal
studies and of the risk of neonatal withdrawal symptoms if used near term.
UKTIS (2012) points out that theoretical concerns exist regarding the
development of PPHN after gestational duloxetine exposure. The
frequency of live born infants with one or more major congenital
malformations was not significantly higher than the background rate.
Mirtazapine:
According to Maudsley guidelines, it is (as yet) not associated with
malformations (based on limited data) but may increase the risk of
spontaneous abortion.
The BNF suggests (a) exercising caution on account of toxicity in animal
studies and (b) monitoring the neonate for withdrawal effects.
UKTIS (2010) reports cases of patent ductus arteriosis, midline facial
defect, cleft lip and palate, hypospadias, tracheomalacia and vesicouretal
reflex although, as yet, there is not an apparently substantially increased
7
risk of congenital malformations following exposure to mirtazapine in
pregnancy.
Neonatal withdrawal symptoms (increased pulse, tremor, increased
breathing rate) have been recorded in one case and also recurrent
hypothermia in a set of twins (UKTIS 2010).
MAOIs:
Maudsley guidelines advise that these drugs should be avoided on
account of suspected increased risk of congenital malformations and the
risk of hypertensive crisis.
The BNF states that manufacturers advise against use unless there are
compelling reasons.
Mianserin:
The BNF states ‘avoid’.
Trazadone:
The BNF states ‘ avoid during first trimester’.
As regards ALL antidepressants, there is a risk of withdrawal or toxicity in
neonates (but these are often mild or self-limiting) and include:
convulsions, crying, poor feeding, hypertonia, respiratory distress.
3.2
Antipsychotics
Note: The BNF proposes that, following maternal use of antipsychotics in
the 3rd trimester, neonates should be monitored for symptoms including
agitation, hypertonia, tremor, drowsiness, feeding problems and
respiratory distress.
Older, first generation antipsychotics (FGAs) are generally considered to
have minimal risk of teratogenicity. Chlorpromazine, haloperidol and
trifluoperazine have been widely used.
There is an extremely low risk of limb defects associated with the use of
haloperidol. Other malformations reported include micropththalmia,
gastroschisis and renal dysplasia (but causality could not be specifically
attributed to haloperidol exposure), the rate of malformations falling within
the expected background range (NTIS 2009). The use of haloperidol (if
clinically efficacious) in the management of acute and chronic psychoses
in pregnancy has been proposed by NTIS (2009).
Neonatal jaundice has been reported with phenothiazines (e.g.
chlorpromazine).
As regards sulpiride, UKTIS (2011) states that ‘the manufacturer cautions
on the risk of extrapyramidal effects, hypotonia and lethargy in neonates
8
following 3rd trimester exposure’. There are case reports (one each) of
mild jaundice and suspected antenatal growth retardation.
Neonatal dyskinesia has been reported with FGAs.
Data regarding the use of atypical antipsychotics is growing. Limited data
suggest that neither risperidone nor quetiapine are teratogenic.
Data regarding amisulpiride is scanty (NTIS 2008).
Aripiprazole has potential teratogenic effects in rats and rabbits. As
regards human data, no adverse effects were reported in 2 published case
reports. As yet, published data are insufficient to offer any risk
assessment (NTIS 2008).
UKTIS (2009) reports perinatal problems associated with the use of
risperidone, including: respiratory difficulties, seizures, prematurity and
jaundice.
UKTIS (2009) suggests that a detailed ultrasound scan should be
considered following first trimester exposure to quetiapine. It also states
that ‘neonatal withdrawal symptoms may be expected following the use of
quetiapine in pregnancy’. (There is a case report of a ‘jittery’ live born
infant with upper limb myoclonus.)
According to the Maudsley guidelines, risks reported regarding the usage
of olanzapine include:









lower birth weight
maternal weight gain
increased admissions (of the neonate) to intensive care
macrosomia (see glossary)
gestational diabetes
hip dysplasia (see glossary)
meningocele (see glossary)
ankyloblepharon (see glossary)
neural tube defects
The BNF suggests the use of olanzapine only if potential benefit
outweighs risk. It highlights that neonatal lethargy, tremor and hypertonia
have been reported when used in the third trimester.
SIGN suggests additional monitoring for blood glucose abnormalities.
UKTIS (2010) reports cases of craniosyntosis, ureteric reflux, hand/finger
reduction, ventricular septum defect and upper alimentary tract
malformation. However, the frequency of congenital malformations in live
born infants was not significantly higher than the background rate. When
olanzapine is used in pregnancy, UKTIS recommends maternal blood
glucose, BP and weight monitoring during pregnancy in addition to fetal
9
growth monitoring. UKTIS (2010) also states that ‘ neonatal withdrawal
symptoms may be expected following the use of olanzapine in pregnancy’.
Reported risks of clozapine include:




gestational diabetes (monitor maternal blood glucose)
neonatal seizures
potential agranulocytosis in the foetus or neonate
increased incidence of malformations (8.2%)
Consider a detailed ultrasound scan following 1st trimester exposure.
NICE recommends a switch to another antipsychotic.
However the Maudsley guidelines point out that this could well result in a
relapse and therefore, in reality, it might actually be best to continue
clozapine.
The BNF suggests using the drug with caution.
Depots should be avoided (NICE recommendation). There is little
information regarding their safety and the dosage cannot be altered once
administered. They may lead to development of extra-pyramidal
symptoms in the infant. However, risks to the service user (resulting from
non-treatment) must still be considered.
3.3
Benzodiazepines
Use only for short-term treatment of extreme anxiety and agitation (no
more than 4 weeks). Use low dose where possible.
Consider gradually stopping benzodiazepines in women who are
pregnant.
With regard to rapid tranquillisation, use a benzodiazepine with a short
half-life.
Evidence is conflicting with regard to the possible increased risk of
congenital malformation following use of diazepam in pregnancy.
The Maudsley guidelines highlight that use in the first trimester may be
associated with an increased risk of oral clefts (0.7%) (see glossary).
Other risks include:





pylorostenosis (see glossary)
alimentary tract atresia (see glossary)
low birth weight
pre-term birth
floppy baby syndrome (third trimester usage)
10

limb defects
Detailed fetal ultrasound scans may be considered following first trimester
exposure (UKTIS 2012).
Alternative options suggested include low-dose chlorpromazine or
amitriptyline as recommended by NICE.
The BNF suggests the avoidance of regular use and prescribing only if
there is a clear indication (e.g. seizure control). There is a risk of neonatal
withdrawal symptoms when used during pregnancy: high doses given in
late pregnancy or during labour may cause neonatal hypothermia,
hypotonia (see glossary) and respiratory depression.
3.4
Lithium
The period of maximum risk to the foetus is 2-6 weeks after conception.
There is an increased risk of foetal heart defects: 60 in 1000 (compared to
8 in 1000 in the general population).
The risk of Ebstein’s anomaly (see glossary) is increased from 1 in 20,000
to 10 in 20,000.
Use in the second and third trimesters has been associated with floppy
baby syndrome, potential thyroid abnormalities and nephrogenic diabetes
insipidus.
Avoid routine prescribing in the first trimester of pregnancy.
If well, and not at high risk of relapse, stop taking lithium when planning a
pregnancy.
Slow (rather than abrupt) discontinuation before conception is the
preferred course of action.
Gradually stop lithium over 4 weeks in a well woman with a pregnancy
confirmed in the first trimester if not at high risk of relapse.
If unwell or at high risk of relapse, the options are:
 gradual switching to an antipsychotic.
 stopping lithium temporarily, restarting in the second trimester if she
does not wish to breastfeed.
 continuing with lithium.
High resolution ultrasound scans and foetal echocardiography should be
done at 6 weeks and 18 weeks gestation in women taking lithium. (NTIS
recommends this at about 20 weeks gestation.)
11
Serum lithium levels should be monitored:
 every 4 weeks until 36 weeks
 weekly from the 36th week
 within 24 hours of childbirth
The levels should be kept towards the lower end of the therapeutic range.
Delivery should be in hospital and fluid balance must be monitored.
Do NOT give during labour.
Risks cited by the Maudsley guidelines include: neonatal goitre, hypotonia,
lethargy and cardiac arrhythmia.
The BNF advises avoidance if possible in the first trimester (risk of
teratogenicity including cardiac abnormalities), increased dosage
requirements in the second and third trimesters (but returning abruptly to
normal following delivery) and the close monitoring of serum lithium
concentration (and the risk of toxicity in the neonate).
SIGN (2012 guidelines) suggests that stopping or reducing lithium prior to
delivery may reduce the risk of complications in neonates. However, there
is, as yet, an absence of evidence to assist decisions on whether to
reduce or discontinue lithium in the time prior to delivery. SIGN does
recommend restarting lithium after delivery in women with bipolar disorder
in order to reduce the risk of relapse.
SIGN recommends the setting up of multidisciplinary shared lithium
management plans to include the frequency of monitoring and dose
adjustment, preparation for and mode of delivery and risks to the neonate.
NTIS (2009) states that toxic effects to the fetus thought to be associated
with maternal lithium exposure are: premature births, perinatal mortality,
fetal macrosomia, lethargy, hypotonia, feeding difficulties and goitre. NTIS
recommends that continued use of lithium should be decided on a
case by case basis. The NTIS (2009) also recommends, if clinically
possible, reducing or discontinuing lithium near term (in order to reduce
the risk of neonatal toxicity).
3.5
Carbamazepine and Lamotrigine
NICE recommends the use of an antipsychotic (with mood-stabilising
properties) as a preferable alternative to continuation with an
anticonvulsant mood stabiliser.
12
The Maudsley states that the best practice guidelines recommend the
lowest possible dose of a single anticonvulsant.
Routine prescribing in pregnancy should be avoided.
It is advisable to stop taking these drugs if planning a pregnancy or having
an unplanned pregnancy.
Use of carbamazepine increases the risk of neural tube defects from 6 in
10,000 in the general population to one of 20-50 in 10,000. In percentage
terms, the risk is about 0.5%.
The overall malformation rate is 2.9%.
Increasing doses are associated with increased risks of malformation.
There is also an increased risk of gastrointestinal problems (0.2%),
cardiac abnormalities (0.7%) facial cleft (0.4%), hypospadias and
microcephaly.
In utero carbamazepine exposure may adversely affect infant
neurodevelopment (UKTIS 2012).
The risk of oral cleft is 9 in 1000 with the use of lamotrigine, which should
not be used routinely in pregnancy according to NICE. The risk in the
general population is 0.37 in 1000.
The BNF gives extensive advice regarding the use of carbamazepine:

increased risk of neural tube and other defects

women who may become pregnant should be informed of the
possible consequences

those who wish to become pregnant should be referred to an
appropriate specialist for advice

women who become pregnant should be counselled and offered
antenatal screening ( alpha-fetoprotein measurement and second
trimester ultrasound scan)

adequate folate supplements advised before and during pregnancy

drug concentrations can change during pregnancy and therefore the
dose should be monitored carefully during pregnancy and after birth

routine injections of vitamin K at birth counteracts any drugassociated risk of neonatal haemorrhage
The advice for lamotrigine is as above. The risk of teratogenesis is
acknowledged. There have been case reports of absent thyroid, small
ventricular septal defect and bladder exstrophy. There is inconsistent
evidence that lamotrigine exposure in utero may be associated with cleft
lip and palate (and that there may be a dose-related relationship).
Detailed ultrasound scans may therefore be considered. From
prospective studies (UKTIS 2010), lamotrigine, used alone, does not
13
appear to cause a higher rate of malformations compared to that in the
general population.
Lamotrigine is subject to significant alterations in metabolism in
pregnancy (clearance increases as pregnancy progresses). There is
therefore a risk of post-partum toxicity as clearance rates return to normal.
Maternal lamotrigine levels must therefore be monitored throughout
pregnancy and in the early postpartum period.
As yet there are no identified effects on infant or child development
including IQ as regards lamotrigine.
3.6
Valproate (Sodium valproate/any valproate preparations)
This is one psychotropic medication to be considered very seriously
in terms of the relatively high risks of established teratogenicity and
long-term consequences for the child.
If planning a pregnancy or pregnant, advise stopping valproate, if possible.
Avoid, if possible, prescribing valproate to women of child-bearing
potential. Otherwise explain the risks of taking this drug during pregnancy
and the importance of adequate contraception.
Avoid using in women under the age of 18 on account of the risk of
polycystic ovary syndrome.
Intra-uterine growth retardation may occur.
The overall major malformation rate may be as high as 10% (UKTIS
2011).
The risk of neural tube defects (e.g. spina bifida and anencephaly) is
increased from 6 in 10,000 pregnancies (in the general population) to 100200 in 10,000 pregnancies. In percentage terms, spina bifida occurs in
0.5 – 1% of pregnancies.
Other potential abnormalities include facial dysmorphias and distal digit
hypoplasia. Atrial septal defect, hypospadius, polydactyly and
craniosynostosis may occur in 0.5%, 0.3%, 0.2% and 0.1% respectively in
pregnancies when this drug is used.
There may be effects on the child’s intellectual development. Data
suggest that 22% of children born to women taking valproate during
pregnancy have an exceptionally low (i.e. less than 70) verbal IQ
(compared to 2% in the general population). Valproate appears to have a
dose-dependent effect on IQ.
14
If absolutely no alternative, give a maximum of 1g daily, in divided doses
and in slow release form. Also prescribe folic acid (5mg daily).
BNF advice is as for carbamazepine as described above. There is an
increased risk of congenital malformations and developmental delay if
used in the first trimester. Counselling and screening are advised.
Neonatal bleeding and neonatal hepatotoxicity have been reported.
3.7
Procyclidine
No specific pattern of malformations has been identified.
Chronic use, or use near term, has been associated with neonatal
withdrawal effects (NTIS 2008).
3.8
Propranolol
Use of propranolol has not been conclusively associated with an
increased risk of structural fetal malformations.
The following have been reported (but no causal link established):
cardiovascular defects
hypospadias
cleft lip or palate
pyloric stenosis
tracheo-oesophageal fistula
crepitus of the hip
intra-uterine growth retardation
Monitoring of fetal growth is recommended (NTIS 2009).
Neonatal problems have been described in a number of case reports:
apnoea
respiratory distress
bradycardia
hypoglygaemia
and these are attributable to beta-adrenoceptor blockade.
When reported, symptoms are usually mild and resolve within 48 hours.
3.9
Promethazine
At therapeutic doses promethazine has not been associated with an
increased risk of congenital abnormalities above the background rate for
the general population.
There is a theoretical risk of neonatal withdrawal symptoms following its
use near to term (UKTIS 2010).
15
4
PRESCRIBING DURING BREASTFEEDING
(This section adapted with kind permission from a document prepared by Ann
Coleman, Pharmacist, CHFT, April 2008)
4.1 General principles:

Avoid all medicines if possible; otherwise encourage treatment options
that would enable a woman to breastfeed if she wishes (rather than
recommending that she does not do so) without compromising mental
health or increasing the risk of relapse.

It is usually inappropriate to withhold treatment to allow breast
feeding where there is a high risk of relapse. Treatment of maternal
illness is the highest priority (Maudsley guidelines 2012).

Check the medicine in a reference source (see list, cited later) and/or
discuss with the locality pharmacist and/or an infant feeding advisor
available for consultation within the Acute Trusts.

Use the medicine with the safest side-effect profile (i.e. avoid medicines
known to have serious toxicity in children or adults).

Use the lowest effective dose possible and also try to avoid
polypharmacy (whereby additive side-effects and drug interactions may
potentially increase the risk).

Infants of breastfeeding mothers taking psychotropic drugs should be
monitored for adverse reactions.

Be aware that certain psychotropic drugs can cause sedation which may
affect the infant’s feeding.

Use medicines with a short half-life and avoid sustained-release
preparations (including depot injections).

Where possible the infant should be fed immediately before the dose.
4.2
If the psychotropic medication is given once a day, time the dose just
before the infant’s longest sleep period (minimising actual concentration in
milk and maximising clearance before the next feed)
4.3
If a short course of medication is to be used that is not compatible with
breastfeeding, milk should be expressed and discarded (with appropriate
advice from the midwife or infant feeding advisor).
4.4
An appropriate length of time should be allowed after stopping the
medicine before recommencing breastfeeding (e.g. five times the
elimination half-life of the drug).
16
4.5
If a medicine is to be used long-term and is NOT compatible with
breastfeeding, then the patient should be referred back to the prescriber
and midwife or infant feeding advisor for support in discontinuing
breastfeeding.
Always weigh up the risk-benefit ratio for both mother and infant.
17
5
PRESCRIBING PSYCHOTROPIC MEDICINES WHILST
BREASTFEEDING
In general, all drugs should be avoided in premature or low birth weight
infants or those who have any underlying conditions.
5.1
Antidepressants
imipramine + nortriptyline
:
:
tacitly recommended by NICE
(Maudsley)
most manufacturers advise TCAs
should be avoided (BNF)
amitriptyline
:
may be considered where a TCA is
clinically appropriate
doxepin
:
:
avoid (SIGN)
may cause respiratory depression,
drowsiness, hypotonia and poor
suckling (Maudsley)
accumulation of metabolite may cause
sedation and respiratory depression in
neonate (BNF)
not suitable for use in lactation; single
report of apnoea and sedation (UK
Drugs in Lactation Advisory Service)
:
:
citalopram
:
:
:
:
escitalopram
:
:
:
:
fluvoxamine
:
:
:
symptoms reported in a minority of
infants (irritability, hypotonia,
colic, irregular breathing)
(Maudsley)
present in milk – use with caution
(BNF)
manufacturers advise against use
long half-life; not suitable for use in
lactation (UK Drugs in Lactation
Service)
nil adverse reports in 8/8
infants studied (Maudsley)
1 recorded case of necrotising
enterocolitis
present in milk – avoid (BNF)
manufacturers advise against use
no adverse effects reported
(Maudsley)
present in milk – avoid (BNF)
manufacturers advise against use
18
fluoxetine
:
suitable for use in lactation (UK Drugs
in Lactation Service)
:
most infants not affected
may cause increased crying,
reduced feeding, diarrhoea +
vomiting, hypotonia, seizures,
reduced sleep
manufacturers advise against use
or, if using, prescribing the lowest
dose (Maudsley)
present in milk – avoid (BNF)
not suitable for use in lactation; long
half-life; irritability and reduced weight
gain reported (UK Drugs in Lactation
Service)
:
:
:
paroxetine
:
:
:
:
:
sertraline
:
:
:
reboxetine
:
:
:
venlafaxine
:
:
one reported case of adverse
effects (vomiting, irritability)
manufacturers advise that its
use can be considered (Maudsley)
suitable for use in lactation (UK Drugs
in Lactation Service)
‘uncertain potential for toxicity in
infants’ (UKTIS 2011)
present in milk but amount too
small to be harmful (BNF)
tacitly recommended by NICE
(Maudsley)
not known to be harmful but consider
stopping breastfeeding (BNF)
suitable for use in lactation;
withdrawal symptoms seen after
abrupt withdrawal of maternal
sertraline (UK Drugs in Lactation
Advisory Service)
no adverse reports in 4 cases
manufacturers advise that use in
breastfeeding can be considered if
the benefits outweigh the risk to
the child (Maudsley)
small amount present in milk – use
only if potential benefit outweighs
risk (BNF)
manufacturers advise against its
use in breastfeeding (Maudsley)
no adverse effects in a study of 13
19
:
infants
present in milk – avoid (BNF)
MAOIs
:
:
no published data (Maudsley)
avoid (BNF)
moclobemide
:
:
no adverse effects listed
manufacturers advise that its use
in breastfeeding can be
considered if the benefits
outweigh the risk to the child
(Maudsley)
amount too small to be harmful,
but patient information leaflet
advises avoid (BNF)
:
mianserin
:
:
mirtazapine
:
:
:
trazodone
:
:
no adverse effects in two infants
studied (Maudsley)
amount of drug secreted into
breast milk too small to be
harmful (BNF)
no adverse effects reported (in
eight infants)
the manufacturers advise against
its use in breastfeeding
(Maudsley)
present in milk; use only if
potential benefit outweighs risk
(BNF)
the manufacturers advise that the
possibility of excretion into breast
milk should be considered
(Maudsley)
amount of drug secreted into
breast milk too small to be
harmful (BNF)
duloxetine
:
no short-term adverse effects reported
(Maudsley)
agomelatine
:
avoid – present in milk in animal
studies (BNF)
20
5.2
Antipsychotics
SIGN advice: All breastfed infants should be monitored for sedation and extrapyramidal adverse effects where mothers are taking antipsychotic medications.
typical antipsychotics
:
:
:
:
amisulpride
:
:
:
aripiprazole
:
:
:
clozapine
:
:
:
:
:
olanzapine
:
:
:
little data overall
chlorpromazine may cause lethargy
no problems reported with
zuclopenthixol (7 infants)
manufacturers of sulpiride advise
against its use in breastfeeding
(Maudsley)
amount present in milk is probably
too small to be harmful, but avoid
unless absolutely necessary
(possible adverse effects on
developing nervous system in animal
studies) (BNF)
no adverse effects in 2 recorded
infants
breastfeeding is contraindicated
by the manufacturers (Maudsley)
avoid – no information available
(BNF)
no problems reported in 1 infant
(Maudsley)
avoid – present in milk in animal
studies (BNF)
manufacturers advise against its use
sedation, agranulocytosis, seizures,
irritability, delayed speech have
been reported (Maudsley)
manufacturers advise against its
use in breastfeeding
avoid (BNF)
SIGN states ‘do not breastfeed’
one report of delayed speech
development (UKTIS)
jaundice, sedation, tremor, irritability
and speech delay have been
reported (Maudsley)
no adverse effects in 4/7 infants
manufacturers advise against its
use in breastfeeding
21
quetiapine
:
avoid – present in milk (BNF)
:
manufacturers advise against its
use in breastfeeding
3 infants unaffected (Maudsley)
avoid – no information available
(BNF)
:
:
risperidone
:
no adverse effects reported in
7/7 cases (Maudsley)
use only if potential benefit
outweighs risk – small amount
present in milk (BNF)
:
5.3
sertindole
:
:
no published data found (Maudsley)
avoid – no information available
(BNF)
sulpiride
:
no adverse effects reported
(Maudsley)
paliperidone
:
avoid – present in milk (BNF)
Benzodiazepines
Benzodiazepines are excreted in breast milk but the levels are low.
Reported adverse effects in some infants include sedation, lethargy and weight
loss (diazepam) and apnoea (clonazepam).
The Maudsley guidelines recommend avoiding benzodiazepines with a long halflife and monitoring infants for central nervous system (CNS) depression and
apnoea.
The BNF recommends avoiding use if possible.
5.4
Lithium
This is excreted in breast milk at a level of around 40% of maternal serum levels.
Adverse effects reported in some infants include cyanosis, lethargy, hypothermia,
hypotonia and heart murmur. There are also other reported cases of no adverse
effects.
According to the Maudsley guidelines, opinions vary from absolute contraindication to mother’s informed choice.
22
Be mindful of the infant’s electrolyte balance and state of hydration and monitor
the infant closely for signs of toxicity (in addition to providing thyroid and renal
monitoring and measuring serum lithium levels).
Breastfeeding is contraindicated by the manufacturers.
NICE recommends that lithium is not routinely prescribed during breast feeding.
The BNF suggests avoiding the use of lithium on account of the risk of toxicity in
the infant.
5.5
Carbamazepine and Lamotrigine
carbamazepine
lamotrigine
:
adverse effects in some infants
include: raised liver function
tests, cholestatic jaundice, drowsiness,
irritability (Maudsley)
:
the manufacturers advise that
breastfeeding can be considered if
the benefits outweigh the risk to
the child (and the infant must be
observed for possible adverse
reactions)
:
the BNF suggests that breast-feeding
is acceptable at normal doses; monitor
the infant for possible adverse
reactions
:
suitable for use in lactation; monitor
infant for adverse events (UK Drugs in
Lactation Advisory Service)
:
advisable to avoid because of the
theoretical risk of life-threatening
rashes (Maudsley) but also no
adverse effects in 30 infants
:
manufacturers advise that the
benefits be weighed against the
risk to the child
:
present in milk but limited data
suggest no harmful effects on
infants (BNF)
:
use with caution in lactation and
monitor infant for adverse effects,
especially rash. Blood level
23
monitoring may be necessary if
exposure prolonged (UK Drugs in
Lactation Advisory Service)
5.6
Valproate (Sodium valproate/any valproate preparations)
Adverse effects reported include thrombocytopenia and anaemia and
there is a theoretical risk of hepatotoxicity (Maudsley).
Manufacturers state that there appears to be no contraindication to its use
in breastfeeding.
The BNF suggests that the amount in milk is too small to be harmful.
UK Drugs in Lactation Service suggests that valproate is suitable for use
in lactation, and that the infant should be monitored for signs of rash.
5.7
Other Drugs
promethazine
:
:
:
Z drugs
(zopiclone, zolpidem,
zaleplon)
:
:
:
clonazepam
6
:
no published data (Maudsley)
manufacturers issue no specific
advice on its use in breastfeeding
not known to be harmful (BNF)
no adverse effects reported
(Maudsley)
manufacturers advise against the
use of all 3 in breastfeeding
BNF recommends avoiding zolpidem
and zopiclone
not suitable for use in lactation (single
case report of apnoea in a breast-fed
infant); avoid unless essential (and
monitor infant closely)
USEFUL INFORMATION SOURCES





The Breastfeeding Network – www.breastfeedingnetwork.org.uk
UK Drugs in Lactation Advisory Service – www.ukmicentral.nhs.uk
BNF for children – www.bnfc.org/bnfc/2009/
2010 Medications and Mothers’ Milk, Thomas W. Hale (worldwide
definitive reference book) ISBN 978-0-9823379-9-8
Drugs in Pregnancy and Lactation (2008), GG Briggs, RK Freeman
and SJ Yaffe, 8th Edition, Lippincott and Williams, Philadelphia
24
7
Glossary of medical terminology
agenesis
lack or failure of development of a body part
agranulocytosis
a failure of the bone marrow to make enough white
blood cells (neutrophils)
anencephaly
a neural tube defect (fatal), leading to absence
of a major portion of the brain, skull + scalp
ankyloblepharon
adhesion of the eyelids to each other or to the
eyeball
APGAR score
method to quickly assess health of newborn
children immediately after childbirth
apnoea
temporary absence or cessation of breathing
atresia
an abnormal condition in which a normal opening
or tube in the body is closed or absent
atrium septum defect
‘hole in the heart’; a hole between the left and right
atria
bladder exstrophy
a birth defect in which the bladder is inside out and
sticks out of the abdominal wall
bradycardia
abnormally slow heart rate
cholestatic hepatitis
jaundice with bile stasis in inflamed intrahepatic bile
ducts
clubfoot
a congenital deformity causing the feet to point down
and inwards
coarctation of the aorta
a narrowing of part of the aorta (the major artery
leading out of the heart)
corpus callosum
a thick band of nerve fibres that bridges the two
hemispheres of the brain
craniosynostosis
premature fusion of fibrous sutures in an infant
skull leading to restricted skull + brain growth
crepitus
a clinical symptom characterised by peculiar cracking
dyskinesia
distortion or impairment of voluntary movement
25
Ebstein’s anomaly
a heart defect in which the tricuspid valve is
abnormally formed and situated
equinovarus deformity
another term for clubfoot
fistula
a permanent abnormal passageway between 2
organs in the body or between an organ and the
exterior of the body
floppy baby syndrome
an abnormal condition in newborns and infants
manifested by inadequate tone of the muscles
gastroschisis
a birth defect in which an infant’s intestines stick out of
the body through a defect on one side of the umbilical
cord
goitre
a swelling in the thyroid gland
hemiplegia
paralysis of one side of the body
hip dysplasia
deformation or misalignment of the hip joint
hypertensive crisis
a severe increase in blood pressure (that can
lead to a stroke)
hypertonia
abnormal increase in muscle tension
hypoglycaemia
low blood sugar
hypoplasia
incomplete development or underdevelopment of an
organ or tissue
hypospadias
a birth defect of the urethra in the male that
involves an abnormally placed urinary opening
hypotension
low blood pressure
hypotonia
abnormally low muscle tone; ‘floppiness’
macrosomia
large for gestational age babies whose birth
weight lies above the 90% percentile for that
gestational age
meningocele
protrusion of the membranes that cover the
spine and part of the spinal cord through a bone
defect in the vertebral column
microcephaly
an abnormally small head (because the brain has not
developed properly or has stopped growing)
26
microphthalmia
one or both eyeballs is abnormally small
myoclonus
brief, involuntary twitching of a muscle or group of
muscles
necrotising enterocolitis the death of intestinal tissue
nephrogenic diabetes
insipidus
a medical condition in which the kidney is
unable to conserve water
omphalocele
an abdominal wall defect (in which the liver and
intestines remain outside the abdomen in a sac);
it arises from a defect in the development of
the abdominal wall muscles
patent ductus arteriosus a persistent communication between the descending
thoracic aorta and the pulmonary artery
polydactyly
having more than five digits in a hand or foot
PPHN
persistence after birth of the high pulmonary
arterial pressure that is characteristic of the
foetal circulation; mortality rate is 10-20%
pyloric stenosis
a narrowing of the pylorus, the opening from the
stomach into the small intestine
tachyarrhythmia
any disturbance of the heart rhythm in which the heart
rate is abnormally increased
tachypnoea
rapid breathing
talipes
a congenital deformity in which the foot is twisted out of
shape or position
tracheomalacia
an abnormal collapse of the tracheal (windpipe) walls
due to softening of the cartilage
ventricular septal defect one or more holes in the wall that separates the right
and left ventricles of the heart
vesicouretal reflux
retrograde flow of urine from the bladder to the kidneys
27
8
References
The Maudsley Prescribing Guidelines in Psychiatry, 11th Edition (2012)
National Institute for Health and Clinical Excellence, Clinical Guideline 45:
Antenatal and postnatal mental health, February 2007 (revised 2007)
Drug Safety Update March 2010, Volume 3, Issue 8
‘Fluoxetine: possible small risk of congenital cardiac defects’
Drug Safety Update May 2010, Volume 3, Issue 10
‘SSRIs + SNRIs: risk of persistent pulmonary hypertension in the newborn’
British National Formulary 63 (March 2012)
BMJ, 26th September 2009, volume 339, p735. Pedersen et al.
‘Selective serotonin reuptake inhibitors in pregnancy and congenital
malformations: population based cohort study’
Psychiatric Bulletin (2007) 31:183. Donnelly and Paton.
‘Safety of selective serotonin reuptake inhibitors in pregnancy’
BJ Psych (2008), 192:338. Oberlander et al. ‘Effects of timing and duration of
gestational exposure to serotonin reuptake inhibitor antidepressants: populationbased study’
BJPsych (2008), 192:344. Ramos et al. ‘Duration of antidepressant use during
pregnancy and risk of major congenital malformations’
BJPsych (2008), 192:333. Newham et al. ‘Birth weight of infants after maternal
exposure to typical and atypical antipsychotics: prospective comparison study’
BMJ, 12th May 2007, volume 334, p1003. O’ Keane and Smith. ‘Depression
during pregnancy’
N Engl J Med (2010), 362:2185 (cited in BMJ 19 June 2010 in Short Cuts:
‘Six malformations associated with valproic acid in pregnancy’)
International Psychiatry (2010), 7:74. Henshaw. ‘Reproductive risk: its role in
maternal mental health’
Management of Women with Mental Health Issues during Pregnancy and the
Postnatal Period (Good Practice No. 14, June 2011), Royal College of
Obstetricians and Gynaecologists
BMJ, 9 June 2012, volume 344, p34. Seshadri et al. ‘Prepregnancy Care’.
BMJ, 4 February 2012, volume 344, p10. ‘SSRIs and persistent pulmonary
hypertension of the newborn’.
28
Lecture notes by Dr. Liz McDonald, Winchester Course, 21st June 2012.
SIGN 127 – Management of perinatal mood disorders, March 2012
National Teratology Information Service – ‘Use of … In Pregnancy’






Amisulpiride
Aripiprazole
Haloperidol
Lithium
Procyclidine
Propranolol
(March 2008)
(March 2008)
(June 2009)
(June 2009)
(March 2008)
(September 2009)
UK Teratology Information Service – ‘Use of … in Pregnancy’




















Amitriptyline
Carbamazepine
Citalopram
Clozapine
Diazepam
Dosulepin
Duloxetine
Escitalopram
Fluoxetine
Lamotrigine
Mirtazapine
Olanzapine
Paroxetine
Promethazine
Quetiapine
Risperidone
Sertraline
Sodium Valproate
Sulpiride
Venlafaxine
(October 2010)
(June 2011)
(August 2012)
(December 2009)
(January 2012)
(January 2012)
(March 2012)
(April 2011)
(April 2011)
(December 2010)
(March 2010)
(November 2010)
(April 2011)
(October 2010)
(December 2009)
(December 2009)
(August 2012)
(June 2011)
(October 2011)
(May 2011)
Dr. M.S. Harkin
Associate Specialist in Psychiatry
The Acute Pathway (Working Age Adults)
The Dales
Calderdale Royal Hospital
Salterhebble
Halifax HX3 0PW
September 2012
29