This article is freely available to all

There is a large body of literature on gestational and neurodevelopmental outcomes after antipsychotic exposure during pregnancy1–4 but, to our knowledge, no report on outcomes following several successive pregnancies and breastfeeding with exposure to the same antipsychotic and anticholinergic drug. We therefore present the unusual case of a woman with continuous use of risperidone and trihexyphenidyl (THP) from 1995 to the present day, during which period she gave birth to 5 healthy children who have now reached adolescence or adulthood.

Case Report

Ms A, a 23-year-old woman, presented to the psychiatry clinic in 1995 with a 1-year history of hearing voices, smiling and laughing to herself, poor personal care, and other behavioral disturbances. There was no history of alcohol or substance use. She was diagnosed with undifferentiated schizophrenia (DSM IV criteria) and was prescribed risperidone uptitrated to 5 mg/d and THP 2 mg/d. She improved with treatment and conceived 6 months later. The pregnancy was unplanned. Her attitude toward the pregnancy was positive. She and her husband chose to continue treatment during pregnancy because they did not wish to risk illness relapse. She complied with all antenatal guidance.

At full term, Ms A delivered a healthy girl at home; the delivery was uneventful and was conducted by a midwife. Six months later, the dose of risperidone was reduced to 4 mg/d; THP was continued at 2 mg/d. This was the treatment regimen on which she conceived for the second time in 1999. The medications were again continued all through pregnancy. The pregnancy and delivery of a girl (again at home) were uneventful.

Six months later, there was a transient relapse into psychosis; this was successfully managed with the addition of olanzapine 5 mg/d. Olanzapine was withdrawn uneventfully 6 months later. While on risperidone 4 mg/d and THP 2 mg/d, she again conceived in 2001, 2004, and 2008 and delivered male children. All deliveries were conducted at home and, again, there were no clinically notable antenatal, intranatal, or postnatal complications.

All 5 children were breastfed for approximately 20–24 months. As far as could be ascertained during follow-up visits, there were no untoward events during pregnancy, delivery, or afterward in any of the pregnancies. All babies were healthy, fed well, and developed well. There were no evident congenital malformations, delays in development, or emotional, behavioral, or neurologic disorders.

At present, Ms A’s children are 26, 23, 22, 19, and 15 years old. The first 3 children have completed their education with good grades and are gainfully employed. The remaining 2 children continue their studies and are faring well academically.

Ms A continues to take risperidone 4 mg/d and THP 2 mg/d. She has maintained excellent adherence to these 2 drugs over the past 28 years.

Discussion

It is generally considered that, in women with schizophrenia, antipsychotic drugs are best continued during pregnancy because the risks associated with antipsychotic exposure are less than the risks associated with untreated psychosis.5 Our patient is unique in the literature for gestational and breastfeeding exposure to risperidone 4 to 5 mg/d and THP 2 mg/d across 5 consecutive pregnancies, in which all deliveries were conducted at home, assisted only by a midwife. Although antipsychotic drug exposure during pregnancy has been associated (without certainty of causality) with a range of adverse gestational and neurodevelopmental outcomes,1–4 there were no adverse outcomes that drew clinical attention in this woman and her offspring. We acknowledge that there is no information on the exact duration of gestation, Apgar score at birth, birth weight, developmental milestones, and other specific details. However, in terms of real-world outcomes, such as need for clinical attention, educational attainment, and occupational functioning, all has apparently been well.

There is no systematic study of THP during pregnancy and lactation, but the anecdotal literature is reassuring.6–8 Of note, risperidone raises serum prolactin and predisposes to menstrual irregularities, including amenorrhea and resultant infertility.9 This was clearly not the case with the patient reported here. Finally, one of us (D.M.) previously reported the uneventful use of risperidone in a woman across 2 consecutive pregnancies.10

Article Information

Published Online: February 1, 2024. https://doi.org/10.4088/PCC.23cr03660
© 2024 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2024;26(1):23cr03660
Submitted: October 21, 2023; accepted November 10, 2023.
To Cite: Mendhekar D, Andrade C. A 26-year follow-up of a woman with 5 consecutive children exposed to risperidone during pregnancy and breastfeeding. Prim Care Companion CNS Disord. 2024;26(1):23cr03660.
Author Affiliations: Neuropsychiatry and Headache Clinic, Delhi, India (Mendhekar); Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India (Andrade).
Corresponding Author: Chittaranjan Andrade, MD, Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India ([email protected]).
Relevant Financial Relationships: Dr Andrade prepares an e-newsletter, the Synergy Times, which is supported by Sun Pharmaceuticals; however, payments are made directly to government-recognized charitable organizations with which Dr Andrade is not involved. Drs Andrade and Mendhekar report no other relevant financial relationships.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information (including dates) has been de-identified to protect anonymity.

  1. Neuropsychiatry and Headache Clinic, Delhi, India
  2. Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India
  3. Corresponding Author: Chittaranjan Andrade, MD, Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India ([email protected]).
  1. Damkier P, Videbech P. The safety of second-generation antipsychotics during pregnancy: a clinically focused review. CNS Drugs. 2018;32(4):351–366. PubMed CrossRef
  2. Andrade C. Major congenital malformations associated with exposure to second-generation antipsychotic drugs during pregnancy. J Clin Psychiatry. 2021;82(5):21f14252. PubMed CrossRef
  3. Andrade C. Gestational and neurodevelopmental outcomes associated with antipsychotic drug exposure during pregnancy. J Clin Psychiatry. 2021;82(5):21f14265. PubMed CrossRef
  4. Andrade C. Attention-deficit/hyperactivity disorder, autism spectrum disorder, and other neurodevelopmental outcomes associated with antipsychotic drug exposure during pregnancy. J Clin Psychiatry. 2022;83(3):22f14529. PubMed CrossRef
  5. Breadon C, Kulkarni J. An update on medication management of women with schizophrenia in pregnancy. Expert Opin Pharmacother. 2019;20(11):1365–1376. PubMed CrossRef
  6. Mendhekar DN, Andrade C. Uneventful use of haloperidol and trihehexyphenidyl during three consecutive pregnancies. Arch Womens Ment Health. 2011;14(1):83–84. PubMed CrossRef
  7. Robottom BJ, Reich SG. Exposure to high dosage trihexyphenidyl during pregnancy for treatment of generalized dystonia: case report and literature review. Neurologist. 2011;17(6):340–341. PubMed CrossRef
  8. Goyal SK, Goel A. Successful use of risperidone, trihexyphenidyl, and paroxetine in pregnancy. Indian J Psychol Med. 2017;39(6):835–836. PubMed CrossRef
  9. Mendhekar D, Lohia D. Risperidone therapy in two successive pregnancies. J Neuropsychiatry Clin Neurosci. 2008;20(4):485–486. PubMed CrossRef
  10. Edinoff AN, Silverblatt NS, Vervaeke HE, et al. Hyperprolactinemia, clinical considerations, and infertility in women on antipsychotic medications. Psychopharmacol Bull. 2021;51(2):131–148. PubMed