Clozapine is an atypical antipsychotic (AAP) used in the treatment of schizophrenia and with psychosis associated with Parkinson’s disease where other antipsychotic drugs are not tolerated or are ineffective.
No studies have specifically assessed rates of adverse pregnancy outcomes following maternal clozapine use in pregnancy. Potential users should be made aware of this lack of data, and the decision to prescribe in pregnancy made on a case-by-case basis.
Studies of antipsychotics (APs)/AAPs as therapeutic classes that include a collective total of ~11,500 exposures do not raise concerns of adverse pregnancy outcomes directly related to use. Although findings relating to stillbirth and preterm delivery rates are conflicting, the studies reporting positive findings for these outcomes were not adequately controlled and further research is therefore required to confirm or refute these associations. Neurodevelopmental outcomes following in utero exposure to APs have not been sufficiently studied to permit any assessment of risk.
In the non-pregnant population, use of AAPs (particularly olanzapine and clozapine) is a risk factor for impaired glucose homeostasis and type 2 diabetes. A single study identified an 8-fold increased risk of gestational diabetes in women taking clozapine during pregnancy. An increased risk of fetal macrosomia and its sequelae following gestational exposure to clozapine is therefore possible.
Use of clozapine and other APs throughout pregnancy or near delivery has been associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug. Delivery should therefore be planned in a unit with neonatal intensive care facilities.
It is important to ensure that maternal mental health conditions are treated appropriately. Where a woman’s illness is well-controlled on clozapine, either prior to conception or during pregnancy, the risk of discontinuing or changing medication, or reducing the dose, should be carefully weighed against the risk of relapse. Where clinically appropriate, clinicians are encouraged to discuss the advantages and disadvantages of continued clozapine during pregnancy with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, clozapine may be prescribed for use in pregnancy.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.