Are antidepressants during pregnancy safe? The answer is in your DNA
Every medication has risks and benefits, and many women understandably worry about taking an antidepressant while pregnant. For most women, the risks to the baby from antidepressants are small, while stopping treatment often leads to depression coming back, which carries its own risks for mother and baby. Pregnancy also changes how the body processes many antidepressants, and your genes influence how large these changes are. This article explains what the evidence shows and how a pharmacogenetic test can help.
How common is depression during and after pregnancy?
Up to one in five women have depression or anxiety during pregnancy or in the year after birth, and many women use antidepressants before, during or after pregnancy. Stopping an antidepressant because of pregnancy is risky: in a study of women with a history of major depression who were well at the start of pregnancy, 68% of those who stopped their antidepressant relapsed during pregnancy, compared with 26% of those who continued. Untreated depression can affect nutrition, sleep, prenatal care and bonding, and is linked with preterm birth and postpartum depression.
Are antidepressants safe during pregnancy?
For most antidepressants, the risk of birth defects is small or not clearly different from that of untreated depression. A large US case-control study compared 30,630 mothers of babies with birth defects with 11,478 mothers of healthy babies. Some individual SSRIs were linked with specific defects, but many of these links became weaker when the researchers took the mothers' underlying depression or anxiety into account. Venlafaxine (Effexor) was linked with the largest number of defects, a finding the authors said needs confirmation. The study concluded that treatment decisions should weigh these risks against the risks of untreated depression or anxiety.
A few points are worth knowing:
- Paroxetine (Paxil) is usually not a first choice in early pregnancy because some studies linked it with a small increase in heart defects.
- Sertraline (Zoloft) is often preferred, partly because it has the most safety data and reaches the baby in lower amounts than citalopram or fluoxetine.
- Late pregnancy: some babies exposed to SSRIs or SNRIs near delivery have temporary jitteriness, feeding or breathing problems in the first days, and there is a small increase in a rare lung circulation problem (persistent pulmonary hypertension of the newborn). Let your delivery team know which medication you take.
Never stop an antidepressant suddenly. If you are pregnant or planning a pregnancy, talk to your health care provider before making any change.
How does pregnancy change antidepressant levels?
Pregnancy changes the activity of several liver enzymes that break down antidepressants. These changes are strongest in the third trimester and return to normal within weeks after delivery, so a dose that worked before pregnancy may become too weak or too strong.
| Enzyme | Change during pregnancy | Antidepressants affected | Possible effect |
|---|---|---|---|
| CYP2D6 | More active | Fluoxetine, paroxetine, vortioxetine, venlafaxine | Lower drug levels; may become less effective |
| CYP2C19 | Less active | Citalopram, escitalopram, sertraline | Higher drug levels; more side effects possible |
| CYP2B6 | More active | Sertraline, bupropion | Partly balances lower CYP2C19 activity for sertraline |
| CYP1A2 | Less active | Fluvoxamine, duloxetine | Higher drug levels; more side effects possible |
For example, fluoxetine levels often fall as pregnancy progresses, which can increase the risk of depression returning. A 2023 study found that women taking antidepressants broken down by CYP2D6 had lower blood levels later in pregnancy and could benefit from dose increases, and that combining genetic testing with blood level monitoring helped individualize treatment. Sertraline levels tend to be more stable because higher CYP2B6 activity partly offsets lower CYP2C19 activity.
How do your genes affect antidepressants in pregnancy?
Your genes set the starting point for how active these enzymes are, and pregnancy shifts them further. The CPIC 2023 antidepressant guideline recommends dose adjustments or alternative drugs based on CYP2D6, CYP2C19 and CYP2B6 results.
CYP2D6
- Poor metabolizers have little or no CYP2D6 activity, so the pregnancy-related increase does not apply to them. They have higher levels of drugs such as paroxetine, fluvoxamine and vortioxetine, and CPIC recommends a lower starting dose or another drug.
- Normal and intermediate metabolizers may see levels of CYP2D6-dependent drugs fall during pregnancy, and some will need a dose increase.
- Ultrarapid metabolizers already clear these drugs quickly, and pregnancy may make them even less effective. CPIC recommends choosing another drug.
As the chart below shows, almost half of North Americans have altered CYP2D6 metabolism.
CYP2C19
- Poor and intermediate metabolizers already clear citalopram and escitalopram slowly; with the pregnancy-related drop in CYP2C19 activity, levels and side effects may rise further. CPIC recommends a lower starting dose for poor metabolizers.
- Rapid and ultrarapid metabolizers (about 30% of people of European ancestry) clear these drugs faster. They may do well during pregnancy, but the same dose can become less effective after delivery, when CYP2C19 activity returns to normal. CPIC recommends another drug for ultrarapid metabolizers.
Over half of North Americans have altered CYP2C19 metabolism (see chart below).
Read more about choosing antidepressants with a DNA test.
What about breastfeeding?
Most antidepressants pass into breast milk in small amounts. Sertraline and paroxetine reach the baby in the lowest amounts and are often preferred while breastfeeding. Because enzyme activity returns to pre-pregnancy levels after delivery, a dose that was increased during pregnancy may need to be lowered again.
Can a pharmacogenetic test help during pregnancy?
Pregnancy can also change the response to medications for epilepsy, bipolar disorder and ADHD. Pharmacogenetic tests such as Pillcheck show how your body processes antidepressants, anxiety and ADHD medications, pain medications, antiepileptics and heart medications. Pillcheck includes a personalized medication action plan from a clinical pharmacist trained in pharmacogenetics, who can help you and your doctor plan medication choices and doses before, during and after pregnancy. Ideally, test before a planned pregnancy, since your genetic results do not change.
Summary
- For most women, the risks of antidepressants in pregnancy are small, and stopping treatment often leads to relapse.
- Paroxetine is usually avoided as a first choice in early pregnancy; sertraline is often preferred.
- Pregnancy increases CYP2D6 activity and decreases CYP2C19 and CYP1A2 activity, so antidepressant levels can change.
- Your CYP2D6, CYP2C19 and CYP2B6 genes determine how large these changes are and whether a dose change or a different drug is needed.
- Pharmacogenetic testing is available in Canada and is covered by many health benefit plans.
Frequently asked questions
Should I stop my antidepressant if I become pregnant?
Not without talking to your health care provider. Stopping often leads to relapse: in one study, 68% of women who stopped relapsed during pregnancy, compared with 26% who continued.
Which antidepressant is safest during pregnancy?
Sertraline is often preferred because it has the most safety data and reaches the baby in lower amounts. Paroxetine is usually avoided as a first choice in early pregnancy. The best choice also depends on what has worked for you before and on your genes.
Do antidepressants cause birth defects?
The risk is small for most antidepressants. Some studies found links between individual drugs and specific defects, but many links weaken when the underlying depression is taken into account.
Why might my antidepressant stop working during pregnancy?
Pregnancy speeds up the CYP2D6 enzyme, which lowers the levels of drugs such as fluoxetine and paroxetine. Your doctor may adjust the dose based on your symptoms, blood levels and genetic results.
Can a DNA test help choose an antidepressant during pregnancy?
Yes. CYP2D6, CYP2C19 and CYP2B6 results show how you process antidepressants and help predict how pregnancy will change your drug levels.
References
Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295(5):499-507.
Anderson KN, Lind JN, Simeone RM, et al. Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects. JAMA Psychiatry. 2020;77(12):1246-1255.
Hendrick V, Stowe ZN, Altshuler LL, et al. Placental passage of antidepressant medications. Am J Psychiatry. 2003;160(5):993-996.
Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68.
Colombo A, et al. Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology. Int Clin Psychopharmacol. 2023. doi:10.1097/YIC.0000000000000520.
Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014;34(2):244-255.
Boone C, Colina C, Pope D. Antidepressant Use Before, During, and After Pregnancy. JAMA Netw Open. 2025;8(1):e2457324.
Dubovicky M, et al. Risks of using SSRI/SNRI antidepressants during pregnancy and lactation. Interdiscip Toxicol. 2017;10(1):30-34.
Dean L. Venlafaxine Therapy and CYP2D6 Genotype. In: Medical Genetics Summaries. National Center for Biotechnology Information (US); 2020.
