Pregnancy and Psychiatry Medications – What's Safe?
Psychiatric illness in pregnancy is common (10–20% prevalence). Untreated illness has risks: maternal relapse, poor prenatal care, substance use, preterm birth, low birth weight, and impaired bonding. Clinical decisions balance maternal stability vs fetal safety.
General Principles
Risk-Benefit Analysis
Both untreated illness and medication exposure carry risks.
Medication Approach
Lowest effective dose is preferred (avoid polypharmacy if possible).
Timing Considerations
1st trimester → organogenesis → highest teratogenic risk.
3rd trimester → risk for neonatal adaptation syndrome or withdrawal.
Important Warning
Avoid abrupt discontinuation of psychiatric meds.
Antidepressants: SSRIs
Sertraline → preferred
Lowest placental transfer.
Citalopram/Escitalopram → safe
But QT risk (dose-dependent).
Fluoxetine → longest data history
But long half-life (risk of neonatal irritability).
Paroxetine → avoid in 1st trimester
Risk of cardiac malformations.
Key risks: Poor neonatal adaptation syndrome (up to 30%) but usually mild and self-limiting.
Antidepressants: Other Classes
SNRIs
Venlafaxine/Duloxetine → relatively safe; may increase risk of hypertension.
Bupropion
Reasonable choice if history of smoking or poor SSRI tolerance.
Mirtazapine
Limited but reassuring data; useful for hyperemesis due to appetite stimulation.

Remember that both untreated depression and medication exposure carry risks. Clinical decisions should be individualized based on patient history and severity of symptoms.
Mood Stabilizers: High Risk Agents
Valproate
Contraindicated (NTDs, cognitive impairment, craniofacial anomalies).
Carbamazepine
NTDs, craniofacial malformations (avoid if possible).

Valproate and carbamazepine should be avoided during pregnancy whenever possible due to significant teratogenic risks.
Mood Stabilizers: Moderate Risk & Safer Options
Lithium
Small increased risk of Ebstein's anomaly (1/1,000–2,000 births), but absolute risk is low.
Monitor levels closely (renal clearance ↑ in pregnancy).
Lamotrigine
Favorable reproductive safety profile, but clearance ↑ in pregnancy → may need dose adjustments.
Lamotrigine is generally considered the safest mood stabilizer option during pregnancy, though dose adjustments may be necessary as pregnancy progresses.
Antipsychotics: Typical & Atypical
Typical Antipsychotics
Haloperidol
Longstanding safety data; generally safe.
Perphenazine
Longstanding safety data; generally safe.
Atypical Antipsychotics
Olanzapine, Risperidone, Quetiapine
Generally safe but ↑ risk of gestational diabetes and weight gain.
Clozapine
Limited use; risk of agranulocytosis and neonatal seizures.
Aripiprazole
Relatively safe, but may reduce prolactin → possible lactation issues.
Monitoring: Glucose tolerance testing and weight gain surveillance recommended.
Anxiolytics & Hypnotics
Benzodiazepines
  • Possible risk of cleft lip/palate (esp. diazepam, alprazolam).
  • 3rd trimester: floppy infant syndrome, withdrawal.
  • If necessary, lorazepam or clonazepam in lowest effective dose.
Buspirone
Limited but reassuring data.
Z-hypnotics
Zolpidem, zaleplon: Limited data, generally avoided if possible.
ADHD Medications
Stimulants
Methylphenidate, amphetamines: possible ↑ risk of preterm birth and low birth weight; not first-line, but may be continued in severe cases.
Atomoxetine
Limited data, generally avoided unless benefits outweigh risks.
Special Considerations
ECT
Safe and effective in severe depression/psychosis during pregnancy.
Breastfeeding
Not always contraindicated; depends on drug transfer into breast milk.
Shared Decision-Making
Involve obstetricians and pediatricians.
Clinical Pearls for Students
Sertraline = safest SSRI
Lamotrigine = safest mood stabilizer
Avoid valproate and carbamazepine
Use lithium cautiously, with monitoring
Antipsychotics are generally safe but watch metabolic effects
Benzos sparingly, avoid chronic use
Case Vignette
A 28-year-old woman with bipolar disorder, well controlled on valproate, presents pregnant at 8 weeks.
Discuss Risks
Discuss risks of continuing vs switching.
Preferred Transition
Lamotrigine or lithium (if needed for mood stabilization).
Collaborative Plan
Collaborative plan with OB and psychiatry.
Medication Risk Tiers During Pregnancy
1
2
3
1
High Risk
Valproate, Carbamazepine, Paroxetine
2
Moderate Risk
Lithium, Benzodiazepines, Stimulants
3
Lower Risk
Sertraline, Lamotrigine, Typical Antipsychotics
This pyramid represents the general risk stratification of psychiatric medications during pregnancy. Clinical decisions should always balance maternal mental health needs with potential fetal risks.
Timing Considerations in Pregnancy
1
First Trimester (0-13 weeks)
Highest teratogenic risk during organogenesis
Avoid: Valproate, Carbamazepine, Paroxetine
2
Second Trimester (14-26 weeks)
Lower teratogenic risk
Monitor: Medication levels (especially Lithium, Lamotrigine)
3
Third Trimester (27-40 weeks)
Risk for neonatal adaptation syndrome
Caution with: Benzodiazepines, SSRIs (potential withdrawal)
Key Takeaways
Balance Risks
Both untreated psychiatric illness and medication exposure carry risks during pregnancy.
Preferred Options
Sertraline (for depression/anxiety), Lamotrigine (for bipolar disorder), and typical antipsychotics have the most favorable safety profiles.
Avoid High-Risk Agents
Valproate and Carbamazepine should be avoided due to significant teratogenic risks.
Collaborative Care
Shared decision-making involving psychiatry, obstetrics, and pediatrics is essential for optimal outcomes.