Is risperidone safe to use during pregnancy in a typical adult woman of child‑bearing age being treated for schizophrenia, bipolar disorder, or autism‑related irritability?

Risperidone Use During Pregnancy

Risperidone can be continued during pregnancy when necessary for maternal psychiatric stability, as the available evidence does not demonstrate an increased risk of major malformations above baseline population rates, though neonatal monitoring for withdrawal symptoms is essential. 1, 2, 3

Evidence Quality and Safety Profile

The safety data for risperidone in pregnancy comes primarily from postmarketing surveillance and prospective cohort studies rather than randomized trials:

• Major malformations: The largest postmarketing review of 713 pregnancies found major organ malformations occurred in 3.8% of prospectively reported cases with known outcomes, consistent with the 1-3% baseline population risk 2. A prospective comparative study of 151 pregnancies exposed to atypical antipsychotics (including 49 risperidone exposures) found only 1 major malformation (0.9%), with no statistically significant difference from unexposed controls 3.

• Spontaneous abortion rate: Occurred in 16.9% of prospectively reported risperidone-exposed pregnancies (excluding induced abortions), which aligns with general population rates 2.

Specific Concerns and Monitoring

Possible Increased Malformation Risk

One important caveat exists: A 2019 review identified risperidone as potentially associated with malformations and recommended it not be considered a first-line agent during pregnancy 4. The retrospectively reported cases in the postmarketing database included 12 pregnancies with major organ malformations, most frequently affecting the heart, brain, and lip/palate 2. However, retrospective reporting introduces significant bias, and the prospective data remain reassuring.

Neonatal Withdrawal and Adaptation

Third-trimester exposure carries risk of neonatal extrapyramidal symptoms and withdrawal-emergent syndrome 1, 2:

• A cluster of cases reported tremor, jitteriness, irritability, feeding problems, and somnolence in neonates 2
• These effects are typically self-limited and transient 2
• The FDA label specifically notes these risks and states risperidone is present in breast milk 1

Low Birth Weight

One prospective study found a 10% rate of low birth weight in atypical antipsychotic-exposed infants compared to 2% in controls (p=0.05) 3. This warrants monitoring of fetal growth throughout pregnancy.

Clinical Decision Algorithm

When risperidone is already effective for symptom control:

• Continue risperidone if it has achieved optimal psychiatric stability 4
• The general principle is that women requiring antipsychotics should continue the medication that has been most effective for symptom remission 4

For newly diagnosed or treatment-naive pregnant patients:

• Consider alternative atypical antipsychotics with more extensive pregnancy data (olanzapine, quetiapine) as first-line options 4
• Risperidone remains an option if other agents have failed or are contraindicated

Monitoring requirements:

• Serial ultrasounds to assess fetal growth and detect structural abnormalities, particularly cardiac defects 2
• Neonatal observation for at least 48-72 hours after delivery for extrapyramidal symptoms, feeding difficulties, respiratory distress, and behavioral changes 1, 2
• Consider pediatric consultation at delivery for high-risk monitoring 2

Critical Pitfalls to Avoid

• Do not discontinue risperidone abruptly in a stable patient due to pregnancy recognition, as maternal psychiatric decompensation poses significant risks including poor prenatal care, substance use, and suicide 4
• Do not assume all atypical antipsychotics carry identical pregnancy risks—risperidone may have a slightly different risk profile than other agents in this class 4
• Do not fail to arrange neonatal monitoring—the withdrawal-emergent syndrome is common enough to warrant systematic observation rather than reactive management 2

Breastfeeding Considerations

The FDA label states that risperidone and its active metabolite 9-hydroxyrisperidone are present in human breast milk, and recommends deciding whether to discontinue nursing or the drug based on its importance to the mother 1. This represents a more cautious stance than the pregnancy data might suggest, reflecting the lack of systematic breastfeeding safety studies.