Is haloperidol (Haldol) safe for use during pregnancy?

Haloperidol Use During Pregnancy

Haloperidol can be used during pregnancy when clinically necessary, but should be reserved for situations where the benefit clearly justifies the potential risk to the fetus, with particular caution regarding third-trimester exposure and neonatal monitoring.

FDA Labeling and Primary Safety Considerations

The FDA drug label for haloperidol states that it "should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus" 1. This reflects the lack of well-controlled studies in pregnant women, though no definitive teratogenic effects have been established in humans 1.

Key Neonatal Risks

Third-trimester exposure carries specific risks that require immediate neonatal monitoring:

• Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery 1
• Reported complications include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders 1
• These symptoms vary in severity—some are self-limited while others require intensive care unit support and prolonged hospitalization 1

Animal and Human Data

• Animal studies at 2-20 times the usual maximum human dose showed increased resorption, reduced fertility, delayed delivery, and pup mortality 1
• Cleft palate occurred in mice at 15 times the usual maximum human dose, though this appears to be a nonspecific stress response rather than predictable human risk 1
• There are isolated reports of limb malformations following maternal haloperidol use during the first trimester, though used in combination with other suspected teratogenic drugs, and causal relationships were not established 1

Clinical Evidence and Practice Patterns

Emergency Department Management

For acute agitation in pregnancy requiring pharmacological intervention, haloperidol has emerged as the preferred agent:

• Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy 2
• High-potency typical antipsychotics like haloperidol are preferred for moderate to severe agitation due to their neutral effects on hemodynamics 2
• The lowest effective dose should be used to minimize unknown risks from multiple doses 2

General Safety Profile

A comprehensive review of antipsychotic use in pregnancy found that "to date, no definitive association has been found between use of antipsychotics during pregnancy and an increased risk of birth defects or other adverse outcomes" 3. However, this same review emphasizes the paucity of information and lack of large, well-designed, prospective comparative studies 3.

Practical Management Algorithm

When haloperidol use is being considered during pregnancy:

1. Risk-Benefit Assessment:

   • Evaluate whether untreated maternal psychiatric illness poses greater risk than medication exposure 1, 3
   • Women with serious psychiatric illness often cannot stop medication without interfering with activities of daily living, especially infant care 3

2. Timing Considerations:

   • First trimester: Use only if clearly necessary, as this is the period of organogenesis when structural defects could occur 1
   • Third trimester: Anticipate potential neonatal complications and arrange appropriate monitoring 1

3. Dosing Strategy:

   • Use the lowest effective dose 2
   • Avoid multiple doses when possible, as fetal risk from repeated exposure remains unknown 2

4. Neonatal Monitoring Plan:

   • Arrange for neonatal observation for extrapyramidal symptoms, withdrawal symptoms, respiratory distress, and feeding difficulties 1
   • Have intensive care support available for severe cases 1

Critical Pitfalls to Avoid

• Do not abruptly discontinue haloperidol in women with schizophrenia or severe psychiatric illness, as uncontrolled maternal disease may pose greater fetal risk than continued medication 3
• Do not combine haloperidol with lithium during pregnancy, as an encephalopathic syndrome with irreversible brain damage has been reported, though causality is not established 1
• Do not assume safety from lack of reported problems—the evidence base remains limited with insufficient large-scale studies 3, 4
• Do not use benzodiazepines or ketamine as alternatives, as these have demonstrated adverse fetal outcomes 2

Alternative Considerations

For mild to moderate agitation in pregnancy, diphenhydramine is an effective sedating agent with minimal adverse effects and may be preferred over haloperidol 2. Second-generation antipsychotics like risperidone are often utilized as second-line therapy 2.

Documentation and Counseling

Women requiring haloperidol during pregnancy should receive counseling that:

• No definitive teratogenic association has been established 3
• Third-trimester exposure requires neonatal monitoring for withdrawal and extrapyramidal symptoms 1
• The decision balances maternal psychiatric stability against theoretical fetal risks 1, 3
• Breastfeeding is not recommended during haloperidol treatment 1