The Challenge: Untreated Depression Is Also Risky
The decision to take or stop antidepressants during pregnancy is one of the most difficult decisions many women face. Both options carry risks. Untreated depression during pregnancy is associated with poor prenatal care, substance use, preterm birth, low birth weight, and impaired mother-infant bonding. Treating depression with antidepressants carries its own potential risks to the fetus.
The key principle is that the risks of untreated depression must be weighed against the risks of medication — and for many women with moderate-to-severe depression, the benefits of treatment outweigh the risks.
SSRIs: The Most Studied Antidepressants in Pregnancy
SSRIs (selective serotonin reuptake inhibitors) are the most commonly prescribed antidepressants and have the most safety data in pregnancy. Overall, SSRIs are not associated with major congenital malformations when used in the first trimester. However, several specific concerns have been raised:
Cardiac Defects and Paroxetine
Paroxetine (Paxil) has been associated with a small increased risk of cardiac septal defects in some studies. The absolute risk is small (from ~1% to ~2% baseline risk), but paroxetine is generally avoided in the first trimester if alternatives are available. The FDA changed paroxetine's pregnancy category from C to D in 2005.
Persistent Pulmonary Hypertension of the Newborn (PPHN)
Several studies have found a small increased risk of PPHN (a serious lung condition in newborns) with SSRI use in late pregnancy. The absolute risk is approximately 3 per 1,000 births (vs. 1–2 per 1,000 in unexposed infants). The FDA issued a safety communication about this risk in 2011.
Neonatal Adaptation Syndrome
Approximately 30% of newborns exposed to SSRIs near delivery experience a transient neonatal adaptation syndrome — jitteriness, irritability, feeding difficulties, and respiratory distress that typically resolves within 1–2 weeks. This is not a reason to stop SSRIs before delivery but should be anticipated by the neonatal care team.
Safety Profile by Drug
| Antidepressant | Relative Safety | Notes |
|---|---|---|
| Sertraline (Zoloft) | Preferred | Most safety data; no consistent signal for major malformations |
| Escitalopram (Lexapro) | Acceptable | Good safety profile; limited data vs. sertraline |
| Fluoxetine (Prozac) | Acceptable | Extensive data; long half-life may reduce neonatal adaptation syndrome |
| Citalopram (Celexa) | Acceptable | Some cardiac concerns at high doses; avoid >40 mg/day |
| Paroxetine (Paxil) | Avoid if possible | Cardiac septal defect signal; FDA Category D |
| Venlafaxine (Effexor) | Acceptable with caution | SNRI; similar profile to SSRIs; withdrawal risk in neonate |
| Bupropion (Wellbutrin) | Acceptable with caution | Some cardiac defect signal in early studies; generally considered acceptable |
| TCAs | Use with caution | Older agents; more side effects; limited modern safety data |
Current Guidelines
The American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA) recommend:
- Women with mild depression may be candidates for psychotherapy alone during pregnancy
- Women with moderate-to-severe depression should be offered antidepressant therapy — the risks of untreated depression outweigh the risks of medication
- Sertraline is generally preferred as the first-line SSRI in pregnancy due to its safety profile
- Paroxetine should be avoided if possible, particularly in the first trimester
- Do not abruptly stop antidepressants without medical guidance — this can precipitate severe depression relapse
References
- Grigoriadis S, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):e321-e341.
- Huybrechts KF, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014;370(25):2397-2407.
- ACOG Committee Opinion No. 757: Screening for Perinatal Depression. Obstet Gynecol. 2018;132(5):e208-e212.
Save up to 80% on this medication
Use a free RxGo discount card at 67,000+ pharmacies — no sign-up, no insurance needed.
About the Author
James Okafor, RPh, MBA
Registered Pharmacist & Health Economics Writer
James Okafor is a registered pharmacist with over 12 years of experience in retail and clinical pharmacy settings. He holds an MBA with a focus on healthcare management and specializes in translating complex drug pricing, formulary, and insurance coverage topics into clear, actionable guidance for patients. Before joining RxGuide, James worked as a clinical pharmacist at a regional hospital system and as a pharmacy benefits consultant for a national PBM. His writing focuses on cost transparency, generic alternatives, and helping patients navigate the U.S. prescription drug system.
View full profile on our Editorial Team page →Get the RxGo app — free prescription discounts on the go
Works at 67,000+ pharmacies · No membership needed