Guidelines for Use of Antipsychotics in Pregnancy

General Principle: Risk-Benefit Analysis is Mandatory

• Maudsley Prescribing Guidelines in Psychiatry, 15th ed.
• Creasy & Resnik's Maternal-Fetal Medicine

When to Continue vs. When to Consider Stopping

First-Generation Antipsychotics (FGAs / Typical Antipsychotics)

• FGAs are unlikely to be major teratogens. Large studies including >6 million women (6,371 prescribed FGAs) found antipsychotics were not major teratogens.
• Initial concern came from studies of hyperemesis gravidarum treated with low-dose phenothiazines; much of the signal was likely attributable to the underlying condition.
• A safety signal for cardiac malformations was noted with chlorprothixene (a rarely used agent); further study is warranted.
• High-potency agents (haloperidol, trifluoperazine) are generally preferred over low-potency phenothiazines in pregnancy because they have less anticholinergic, antihistaminergic and hypotensive effect.
• Minimize doses near delivery to reduce the need for antiparkinson drugs (which have their own risks).
• Maudsley Prescribing Guidelines, 15th ed.

Second-Generation Antipsychotics (SGAs / Atypical Antipsychotics)

General SGA risks:

• Not major teratogens overall; large controlled studies did not confirm meaningful overall malformation risk after propensity-score adjustment.
• Preterm birth: associated with increased risk (OR ~1.35-1.86 across studies).
• Low birth weight: associated risk (OR ~2.4 in one meta-analysis).
• Gestational diabetes: significantly increased - especially with clozapine, olanzapine, and quetiapine; aripiprazole may not increase this risk.
• Caesarean section, large for gestational age, and postpartum bleeding risk all modestly elevated.
• Neonatal withdrawal/discontinuation syndrome: crying, agitation, increased suckling - generally mild and transient; considered a class effect.
• Persistent pulmonary hypertension of the newborn (PPHN): increased risk, especially with late-pregnancy exposure; absolute risk is low.

Individual SGA profiles:

• Maudsley Prescribing Guidelines, 15th ed.; Creasy & Resnik's Maternal-Fetal Medicine

Maudsley Box 7.2: Prescribing Recommendations for Psychosis in Pregnancy

1. Pre-conception counselling: Women on antipsychotics who plan pregnancy should discuss this as early as possible.
2. Lifestyle risk reduction: Support women to minimise smoking, alcohol, and drug misuse; refer to cessation services.
3. Hyperprolactinaemia: Consider switching drug if hyperprolactinaemia is preventing conception.
4. Stable patient: If stable on antipsychotic and likely to relapse without it, advise continuation. Switching is generally not advised owing to relapse risk.
5. Initiating treatment: Use the agent that has previously worked best for that woman. This minimises fetal exposure by reducing the likelihood of dose escalation or polypharmacy.
6. Lowest effective dose, fewest drugs: Be clear about indications; do not continue ineffective medication.
7. Diet and weight: Monitor for excessive weight gain; dietary advice.
8. Gestational diabetes screening: NICE (UK) recommends an oral glucose tolerance test (OGTT) for women on antipsychotics.
9. Depot preparations: NICE recommends avoiding depots in women planning pregnancy, currently pregnant, or breastfeeding - unless responding well and have a history of non-adherence with oral medication.
10. Ultrasound: Australian COPE guidelines recommend a 13- or 18-20 week ultrasound for women taking antipsychotics in the first trimester.
11. Neonatal plan: Recommend delivery in a unit with access to paediatric intensive care. Monitor neonate for withdrawal effects. Some centres use mixed (breast/bottle) feeding to minimise withdrawal.
12. Documentation: Document all prescribing decisions, including the medication plan.

Pharmacokinetic Considerations in Pregnancy

• Blood volume expands ~30% in the third trimester, reducing plasma levels.
• CYP2D6 activity increases by ~50% towards end of pregnancy (affects many antipsychotics including risperidone, haloperidol, aripiprazole).
• CYP1A2 activity is reduced by up to 70% (affects clozapine and olanzapine - levels may fall if CYP1A2 is induced by smoking, or rise after smoking cessation).
• Plasma level monitoring is recommended where available, and especially for clozapine.
• Maudsley Prescribing Guidelines, 15th ed.

Neonatal Monitoring After Delivery

• Withdrawal/discontinuation symptoms: agitation, crying, increased suckling (class effect)
• Extrapyramidal symptoms
• Neonatal seizures (especially if exposed to clozapine)
• Hypotonia
• Respiratory distress / PPHN (particularly with late-pregnancy exposure)
• Hypoglycaemia (with metabolic-risk SGAs)

Most Recent Evidence (2026 Meta-Analysis)

• Congenital malformations: borderline association (OR 1.27; 95% CI 0.996-1.624; p=0.054) with moderate heterogeneity - not a major teratogen.
• Limiting to SGAs only: no significant association (OR 1.16; 95% CI 0.78-1.72).
• Preterm birth: significantly associated (OR 1.35; 95% CI 1.13-1.62; p<0.01), with moderate-to-high heterogeneity.
• Conclusion: risks to the fetus must be weighed against risks of discontinuing treatment (including relapse in women with severe mental illness).

Summary: Decision Framework

Does the woman have severe mental illness requiring antipsychotic treatment?
    YES → Continue treatment; do NOT abruptly discontinue
    
Is she on the best-tolerated, most effective agent for her?
    NO → Switch before pregnancy if possible (not during, due to relapse risk)
    
Which agent?
    - Prefer one with the largest safety data (haloperidol, olanzapine, quetiapine)
    - Avoid cariprazine
    - Use lowest effective dose
    - Avoid polypharmacy

Monitor:
    - Gestational diabetes (OGTT)
    - Weight gain
    - Fetal growth scans
    - Plasma levels (adjust for pharmacokinetic changes)
    - Neonatal withdrawal after delivery

Sources: Maudsley Prescribing Guidelines in Psychiatry, 15th ed. | Creasy & Resnik's Maternal-Fetal Medicine | Katzung's Basic & Clinical Pharmacology, 16th ed. | Quinn et al. 2026 meta-analysis (PMID 41504774) | RCPsych/NICE guidance