(Date of issue: March 2015. Version: 2)
This factsheet has been written for members of the public by the UK Teratology Information Service (UKTIS). UKTIS is a not-for-profit organisation funded by Public Health England on behalf of UK Health Departments. UKTIS has been providing scientific information to health care providers since 1983 on the effects that medicines, recreational drugs and chemicals may have on the developing baby during pregnancy.
What is it?
Clozapine (Clozaril®, Denzapine®, Zaponex®) belongs to a group of medicines called atypical antipsychotics and is used to treat schizophrenia and psychosis caused by Parkinson’s disease.
Is it safe to take clozapine in pregnancy?
There is no yes or no answer to this question. When deciding whether or not to take clozapine during pregnancy it is important to weigh up how necessary clozapine is to your health against the possible risks to you or your baby, some of which will depend on how many weeks pregnant you are. Remaining well is particularly important during pregnancy and while caring for a baby. For some women treatment with clozapine in pregnancy may be necessary.
This leaflet summarises the scientific studies relating to the effects of clozapine on a baby in the womb. It is advisable to consider this information if you are pregnant or considering a pregnancy in the future. Your doctor is the best person to help you decide what is right for you and your baby.
What if I have already taken clozapine during pregnancy?
If you have taken or are taking any medicines it is always a good idea to let your doctor know that you are pregnant so that you can decide together whether you still need the medicines that you are on and, if so, to make sure that you are taking the lowest dose that works and only for as long as you need to.
It is very important that you do not suddenly stop taking clozapine as this could be dangerous to you and to your baby if you are already pregnant. Do not make any changes to your medication without first talking to your doctor.
Can taking clozapine in pregnancy cause birth defects in the baby?
A baby’s body and most internal organs are formed during the first 12 weeks of pregnancy. It is mainly during this time that some medicines are known to cause birth defects.
No studies have specifically investigated the occurrence of birth defects in babies of women who took clozapine.
There are however, several studies that have measured how often birth defects occurred in babies born to groups of women who took any type of antipsychotic medicine during pregnancy. The antipsychotic medicines that women were taking often differ from one study to another. Some of these studies included only a small number of women taking clozapine and they could therefore not be studied separately. The findings of studies on antipsychotics in general may therefore not be directly relevant to women taking clozapine but are summarised below for interest:
• Three studies showed that women taking any antipsychotic had an increased chance of having a baby with a birth defect, but two further studies found no link between antipsychotic use in early pregnancy and having a baby with a birth defect.
• One study found that around three in every hundred women who took an atypical antipsychotic in pregnancy had a baby with a heart defect compared to one in every hundred women who did not take any medication in pregnancy. No other studies have investigated this and it is therefore not yet clear whether there is a link between atypical antipsychotic use in early pregnancy and heart defects. This finding may simply be because babies who were exposed to antipsychotics in the womb are more likely to have a heart scan after birth, and abnormalities that would otherwise not have been known about are therefore picked up. Even if it is shown one day that women who take atypical antipsychotics are at increased risk of having a baby with a heart defect, this study suggests that 97 out of every 100 babies born to women taking atypical antipsychotics during pregnancy will not have a heart defect.
Taken together, these studies do not prove that taking antipsychotics during early pregnancy causes birth defects in the baby. Although clozapine is chemically similar to some of the other antipsychotics, it may affect a baby in the womb differently. We therefore do not know whether the findings from studies of antipsychotics as a group relate to women taking clozapine and it is very important that information continues to be collected from women who take clozapine in pregnancy.
Can taking clozapine in pregnancy cause miscarriage?
No studies have specifically investigated whether women who take clozapine during early pregnancy are at increased risk of miscarriage.
No increased risk of miscarriage was seen in any of three studies of pregnant women taking any antipsychotic. Some of the women in these studies were taking clozapine but were not studied separately so we do not know how this information relates specifically to pregnant women taking clozapine.
Can taking clozapine in pregnancy cause stillbirth?
No increased risk of stillbirth was seen in one study of pregnant women taking clozapine. Nor have the five studies of pregnant women taking any antipsychotic medicine shown an increased risk of stillbirth. However, stillbirth rates need to be studied in a larger number of pregnant women specifically taking clozapine before conclusions can be drawn.
Can taking clozapine in pregnancy cause preterm birth?
No studies have specifically investigated whether women who take clozapine during early pregnancy are at increased risk of preterm birth.
Some, but not all studies of pregnant women taking any antipsychotic have shown an increased risk of preterm delivery. It is therefore not yet clear if use of clozapine or another antipsychotic medicine in pregnancy could affect whether or not a baby is born early. More information on individual antipsychotics is needed.
Can taking clozapine in pregnancy affect a baby’s growth in the womb (and birth weight)?
Studies of whether use of clozapine or other antipsychotics in pregnancy might lead to an increase or decrease in the baby’s birth weight have produced mixed results. These studies are summarised below:
Low birth weight
There is no evidence from either of two small studies that clozapine use in pregnancy increases the chance of having a low birth weight baby (<2500g).
Four studies of pregnant women taking any antipsychotic suggested an increased risk of having a baby with a low birth weight, but a further two studies have not agreed with this.
Increased birth weight
Weight gain, high blood sugar and diabetes are common side-effects of clozapine in non-pregnant individuals. If these problems occur in pregnancy they can in turn, cause increased growth of a baby in the womb. Gestational (pregnancy) diabetes has been reported in pregnant women taking clozapine and other atypical antipsychotics. Some small studies have also suggested that clozapine and other atypical antipsychotics may be linked to having a baby that is larger than expected for the stage of pregnancy. However, other studies have found no clear difference in the birth weights of babies born to women taking clozapine or other atypical antipsychotics.
Because the findings of these studies do not agree, it is not yet clear whether clozapine and other antipsychotics can affect a baby’s growth in the womb. Larger groups of women need to be studied using better methods that take into account other factors that might affect birth weight (such as the mother’s weight at conception and whether the baby was born at full term) to answer this question.
Can taking clozapine in pregnancy cause other health problems in the child?
Withdrawal symptoms at birth (‘neonatal withdrawal’)
Withdrawal symptoms are thought to occur as the newborn baby’s body has to adapt to suddenly no longer getting certain types of medicines through the placenta.
Taking clozapine and other antipsychotics during pregnancy can lead to neonatal withdrawal. Close monitoring of your baby for a few days after birth may therefore be advised if you have taken clozapine regularly in the weeks before delivery.
Learning and behavioural problems
A baby’s brain continues to develop right up until the end of pregnancy. It is therefore possible that taking certain medicines at any stage of pregnancy could have a lasting effect on a child’s learning or behaviour.
No link with learning and behavioural problems (e.g. autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)) is known about in children who were exposed specifically to clozapine while in the womb, however no studies have been carried out to specifically investigate this.
One study has analysed learning and behaviour in children whose mothers were treated with any antipsychotic medicine during pregnancy. While babies of mothers who had taken antipsychotics during pregnancy were slightly slower in their development initially, by the time they were one year old there were no differences in developmental test scores between children exposed to antipsychotics in the womb and children who had not been exposed.
Another small study showed that six month old babies who had been exposed to an antipsychotic in the womb tended to achieve lower scores in developmental tests than babies not exposed to antipsychotics. The babies were not studied again at a later age so we do not know if there were any longer-term effects.
More research is needed to assess the long term development of children exposed in the womb to each different antipsychotic.
Will my baby need extra monitoring?
Most women will be offered a scan at around 20 weeks of pregnancy to look for birth defects as part of their routine antenatal care. Taking clozapine in pregnancy would not normally require extra monitoring of your baby.
Weight gain and increased blood sugar (hyperglycaemia) can be side-effects of clozapine. If you are treated with clozapine during pregnancy your doctor may suggest extra monitoring of your weight and blood sugar levels. If you are gaining more weight than expected, or have high blood sugar levels, extra monitoring of your baby’s growth may be advised as these can be linked to having a bigger baby which may affect where and when your baby is delivered.
If you have taken clozapine in the weeks before delivery your baby may require extra monitoring after birth because of the possible risk of neonatal withdrawal. Babies who are large at birth may also need to have their blood sugar monitored for a few days.
Are there any risks to my baby if the father has taken clozapine?
We would not expect any increased risk to your baby if the father took clozapine before or around the time you became pregnant.
Who can I talk to if I have questions?
If you have any questions regarding the information in this leaflet please discuss them with your health care provider. They can access more detailed medical and scientific information from www.uktis.org.