Which antidepressants will work best for your postpartum depression?

Becoming a parent brings joy, but also exhaustion, worry and, for many, guilt. In the first days after birth, many mothers have the “baby blues”: mood swings, tearfulness, anxiety and trouble sleeping that ease on their own within about two weeks. When low mood, loss of interest or anxiety last longer, become more intense, or make it hard to function, it may be postpartum depression. The good news is that postpartum depression is treatable. Here is what to know about antidepressants after birth and while breastfeeding, a new fast-acting treatment, and how your genes can help guide the choice of medication.

What is postpartum depression, and how common is it?

Postpartum depression is depression that starts during pregnancy or in the months after birth, most often in the first few weeks but at any time in the first year. Symptoms include persistent sadness or emptiness, loss of interest or pleasure, feeling disconnected from the baby, anxiety or panic, guilt or feelings of worthlessness, changes in sleep and appetite beyond what a newborn explains, and thoughts of self-harm.

It is common. In a 2019 Statistics Canada survey, 23% of new mothers reported feelings consistent with postpartum depression or an anxiety disorder. Partners can be affected too: about 1 in 10 fathers have depression during pregnancy or in the year after birth.

Postpartum depression is not your fault. Pregnancy changes the brain, and after birth, levels of estrogen, progesterone and the related brain steroid allopregnanolone drop sharply within days. Researchers think that some people are more sensitive to this sudden change, and that sleep loss, stress, a past history of depression and limited support add to the risk.

When should I get help right away?

Speak to your doctor, midwife or nurse practitioner if symptoms last more than two weeks or make it hard to care for yourself or your baby. Get help immediately (call 9-1-1 or go to the nearest emergency department) if you have thoughts of harming yourself or your baby, or if you or your family notice confusion, seeing or hearing things that are not there, or very unusual beliefs or behaviour. These can be signs of postpartum psychosis, a rare (about 1 to 2 in 1,000 births) but serious condition that needs urgent care. In Canada, you can also call or text 9-8-8, the suicide crisis helpline, at any time.

How is postpartum depression treated?

For mild to moderate depression, talk therapy such as cognitive behavioural therapy or interpersonal therapy, peer support and practical help with sleep and baby care are often the first step. For moderate to severe depression, or when therapy alone is not enough, an antidepressant is usually recommended, often alongside therapy. You should not feel guilty about taking medication if that is what you and your health care provider decide.

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, escitalopram, citalopram and paroxetine, are the most commonly used antidepressants after birth. A Cochrane review found that women with postpartum depression who took an SSRI were more likely to respond and to recover than those who took a placebo, although the trials were small. As with other antidepressants, it usually takes two to six weeks to feel the full benefit. If you have taken an antidepressant that worked well for you in the past, it is often a good first choice again. To compare options, read What is the best medication for anxiety and depression?

Which antidepressants are safest while breastfeeding?

Treating depression matters for both parent and baby: untreated postpartum depression can affect bonding, feeding and the child’s development. Most antidepressants pass into breast milk only in small amounts, and the newer antidepressants have not been linked to serious harm in breastfed babies. Experts generally consider an infant dose of less than 10% of the mother’s weight-adjusted dose to be acceptable.

• Sertraline and paroxetine reach breast milk in very low amounts and are often preferred while breastfeeding.
• Citalopram, escitalopram and venlafaxine reach somewhat higher, but usually still acceptable, levels.
• Fluoxetine has a long-lasting active form that can build up in the baby, so it is usually not a first choice to start while breastfeeding, although continuing it after pregnancy may be reasonable.

Source: Chad L, et al. Update on antidepressant use during breastfeeding. Canadian Family Physician 2013;59(6):633-634.

The antidepressant that has worked best for the mother is often the right choice, even if it is not the one with the lowest milk levels. Watch your baby for unusual sleepiness, poor feeding or irritability, and tell your health care provider if you notice any. LactMed, a free database from the U.S. National Library of Medicine, has up-to-date information on individual medications.

How do my genes affect antidepressants after birth?

How quickly your body breaks down an SSRI depends partly on your genes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for antidepressants gives dosing advice based on two liver enzymes:

• CYP2C19 for sertraline, citalopram and escitalopram. Poor metabolizers have higher drug levels and may need a lower dose or a different medication, while ultrarapid metabolizers may get little benefit from citalopram or escitalopram.
• CYP2D6 for paroxetine and fluvoxamine. Poor metabolizers may need a lower dose, and ultrarapid metabolizers may be better served by a different antidepressant.

This matters even more after birth. Time is critical when a new parent is struggling, and a medication that is cleared too fast may not work, which can mean weeks lost before trying another. A medication that is cleared too slowly can cause side effects, and because milk levels follow the mother’s blood levels, it may also mean more medication in breast milk. Knowing your metabolizer status helps your prescriber choose an antidepressant and dose that are more likely to work the first time.

Is there a faster treatment for postpartum depression?

Yes. In December 2025, Health Canada authorized zuranolone (Zurzuvae), the first medication approved in Canada specifically for moderate or severe postpartum depression in adults. It is a pill taken once a day for 14 days. Zuranolone acts like the brain steroid allopregnanolone, which drops after birth. In a clinical trial in women with severe postpartum depression, zuranolone improved symptoms more than placebo as early as day 3, and the benefit lasted through day 45. The most common side effects were sleepiness, dizziness and sedation, so the product labelling warns about driving and other activities that need alertness.

Zuranolone is broken down mainly by the liver enzyme CYP3A4, so other medications that block or speed up this enzyme can change its levels. There is no genetic dosing guidance for zuranolone yet. An earlier treatment in the same family, brexanolone, was given as a 60-hour intravenous infusion in hospital and is no longer marketed.

How can a Pillcheck test help?

A Pillcheck test reports CYP2C19 and CYP2D6, the genes CPIC uses to guide SSRI dosing, along with CYP3A4 and other genes involved in many antidepressants and other medications. A pharmacist reviews your results together with all your medications, and your report can be shared with your doctor to help avoid a trial-and-error approach when choosing an antidepressant. Results can also guide pain medications after birth, such as codeine and tramadol, which CYP2D6 activates.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• Postpartum depression is common, treatable and not your fault. About 1 in 4 new mothers in Canada report symptoms of postpartum depression or anxiety.
• Seek help right away for thoughts of self-harm or harming your baby, or signs of postpartum psychosis. In Canada, call or text 9-8-8.
• Talk therapy is often the first step for mild to moderate depression; SSRIs are the most common medications for moderate to severe depression.
• Most antidepressants, especially sertraline and paroxetine, pass into breast milk in small amounts.
• CYP2C19 and CYP2D6 results help choose an SSRI and dose that are more likely to work the first time.
• Zuranolone, a 14-day pill, is now approved in Canada for moderate or severe postpartum depression.

Frequently asked questions

Can I breastfeed while taking an antidepressant?

In most cases, yes. Most antidepressants pass into breast milk in small amounts, and many parents breastfeed safely while taking them. Talk to your doctor or pharmacist about the best option for you and your baby.

How long will I need to take an antidepressant?

Usually for at least 6 to 12 months after you feel well, to lower the risk of relapse. Do not stop suddenly; your prescriber can help you taper slowly when the time is right.

Can I take zuranolone while breastfeeding?

Information is still limited. Discuss the benefits and risks with your prescriber before starting.

Can a genetic test tell me which antidepressant will work?

No test can guarantee a response. Pharmacogenetic results show how your body processes specific antidepressants, which helps your prescriber avoid medications and doses that are less likely to suit you.

References

Statistics Canada. Maternal mental health in Canada, 2018/2019. 2019.

Paulson JF, Bazemore SD. Prenatal and postpartum depression in fathers and its association with maternal depression: a meta-analysis. JAMA. 2010;303(19):1961-1969.

Hoekzema E, et al. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci. 2017;20(2):287-296.

Molyneaux E, Howard LM, McGeown HR, Karia AM, Trevillion K. Antidepressant treatment for postnatal depression. Cochrane Database Syst Rev. 2014;(9):CD002018.

Chad L, Pupco A, Bozzo P, Koren G. Update on antidepressant use during breastfeeding. Can Fam Physician. 2013;59(6):633-634.

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.

Deligiannidis KM, Meltzer-Brody S, Maximos B, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. 2023;180(9):668-675.

National Library of Medicine. Drugs and Lactation Database (LactMed).