Which Medications Work Best to Treat Postpartum Depression?

You’ve probably heard of the “baby blues” — feelings of sadness or mood changes that occur within a few days of giving birth. But, for some people, there’s also a more serious and longer-lasting period of depression after childbirth. This is postpartum depression (PPD), and it affects up to 20% of women after childbirth. PPD also affects men and adoptive parents. 

Although it can feel hard to reach out for help, treating PPD is important for you and your new baby. And you have options. Therapy and medications — Zurzuvae (zuranolone) and antidepressants — are the main treatments for PPD. Everyone experiences PPD differently, so it’s important to work with your healthcare team to find what works best for you.

What is postpartum depression (PPD)?

Many people experience mood changes after giving birth, but those feelings tend to go away within a week or two. PPD is when those feelings last longer and are sometimes more severe — interfering with your daily life and your ability to care for yourself and your new baby. 

PPD causes feelings of emptiness, sadness, or hopelessness that last for at least 2 weeks. Other common symptoms include:

• Feeling irritable

• Crying a lot

• Feeling anxious, especially about your ability to care for your baby

• Having a hard time connecting with your baby

• Feeling disconnected from friends and family 

• Having changes in your energy and appetite 

• Experiencing “brain fog” (having trouble thinking clearly)

• Having thoughts about harming yourself or your baby

These symptoms can range from mild to severe. They usually begin 1 to 3 weeks after childbirth, but they can show up any time within the first year. In the time after birth, some people can also have a postpartum anxiety disorder, like postpartum panic disorder or postpartum generalized anxiety.

Quiz: Do I have postpartum depression?

What causes PPD?

Researchers don’t know for sure what causes PPD, but there are some things that might make it more likely. Having depression during pregnancy is the biggest risk factor. But other things also seem to matter, like if your pregnancy went well and whether you have a good support network.

There are also many life changes that come along with having a baby. New challenges can make you feel constantly overwhelmed, and you may feel exhausted from lack of sleep. The stress caused by these changes can potentially contribute to PPD.

Changing hormones may also be a trigger for PPD symptoms. When you’re pregnant, your body makes high levels of progesterone and estrogen. But those high levels drop quickly in the first 24 hours after your baby is born. Some researchers think this may lead to depression symptoms.

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• Do postpartum probiotics work? They may help prevent and treat mastitis. And there’s early research that postpartum probiotics can even help with postpartum depression (PPD).

• How long does PDD last? PPD affects everyone differently. Symptoms typically show up within weeks to months after giving birth and can last for months to years. 

• Coping with PPD: Medications aren’t your only option when it comes to managing PPD. From exercise to support groups, these tips can help you cope.

Which medications are used to treat postpartum depression and anxiety?

A lot of PPD research has centered around existing treatments for depression and anxiety, like antidepressants. These medications aren’t specifically FDA approved to treat PPD, but they’re often prescribed off-label. 

If you have mild to moderate PPD, psychotherapy is usually the best first treatment (more on therapy options below). Creating a support network, taking parenting classes, and exercising (if you enjoy it) can also help you overcome PPD. For many people, medication can also be helpful.

Here, we’ll cover medications that your healthcare team might prescribe if you’re diagnosed with PPD. Keep in mind that it can take some time and patience to find the right medication. Many people need to try different medications to get symptom relief.

Good to know: Studies have shown that people under age 25 have a higher risk of suicidal thoughts and behaviors when taking antidepressants. The FDA requires all antidepressants to have a warning about this in the product information.

1. Zurzuvae (Zuranolone)

In 2023, Zurzuvae (zuranolone) became the first oral medication approved to treat PPD. It helps regulate mood by balancing certain chemicals in the brain. Usually, you can take it once a day in the evening with food for 2 weeks. 

In comparison to antidepressants, an advantage of Zurzuvae is that it starts to work quickly. And clinical studies show the effects last for at least 45 days. Zurzuvae hasn’t been compared with selective serotonin reuptake inhibitors (SSRIs) in clinical studies. But data analysis suggests it’s more effective in treating PPD symptoms.

Zurzuvae can affect your mental alertness for at least 12 hours after each dose. Other side effects include: 

• Dizziness

• Diarrhea

• Urinary tract infections

• Common cold symptoms

Zurzuvae may also cause suicidal thoughts in some people.

Since it’s a newer medication, you may need to get special approval from your insurance company to cover the cost of Zurzuvae.

2. Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are FDA approved for many conditions, including depression and anxiety. They’re also used off-label for PPD. 

SSRIs mostly work by affecting serotonin, a brain chemical that may play a role in mood. But researchers have studied some SSRIs for PPD treatment, including:

• Paroxetine (Paxil)

• Fluoxetine (Prozac)

• Sertraline (Zoloft)

A 2013 study compared sertraline to placebo (a pill with no medication in it) for PPD treatment. The group that took sertraline had significantly higher rates of remission — a period of no depression symptoms.

If you’re nursing, the benefits of taking an SSRI generally outweigh the risks. This is especially true if you’ve had success with SSRI treatment for depression in the past. Sertraline is a common option, since less of it seems to get into breast milk. Your healthcare team can help you weigh your options. 

When starting an SSRI, it may take 3 to 4 weeks or more before you experience symptom relief. And, if it works, you’ll likely need to continue taking it for 6 months to 1 year. If you don’t have symptoms after that, your healthcare team may recommend slowly lowering your dose and eventually stopping the medication. 

SSRIs are generally well-tolerated medications without many long-lasting side effects. The biggest exceptions are sexual side effects, which are more likely to hang around if they do appear.

3. Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are another type of antidepressant that are often used off-label to treat PPD. They mostly work by raising serotonin and norepinephrine — another brain chemical.

Venlafaxine (Effexor) is an example of an SNRI sometimes used to treat PPD. A small 2001 study looking at venlafaxine for PPD found that 12 out of the 15 participants taking the medication experienced PPD remission after 8 weeks of treatment. There are no randomized, controlled trials to compare venlafaxine with placebo for treatment of PPD.

SNRIs are usually only used if SSRIs aren’t helping or if an SNRI worked for you in the past. 

There’s also evidence to suggest that venlafaxine may be a good option while nursing, although data is limited. 

SNRIs have overlapping side effects with SSRIs, but they can cause more of the following:

• Nausea

• Sleeping problems

• Dry mouth

• Blood pressure changes

Like SSRIs, most side effects go away with time.

4. Wellbutrin (Bupropion)

Wellbutrin (Bupropion) is an antidepressant that’s FDA approved for major depressive disorder and seasonal affective disorder (SAD). It raises the amount of certain brain chemicals (norepinephrine and dopamine) that likely play a role in mood. But researchers don’t fully understand how this works.

A small 2005 study looking at bupropion for PPD showed significant improvement in depression symptoms. But the researchers noted that the chance of PPD remission was more likely with sertraline or venlafaxine treatment. There’s still very little data on bupropion for treatment of PPD.

Bupropion may also be a treatment option while nursing, but only if switching to another medication isn’t possible or recommended. Other medications have better safety data.

Side effects of bupropion are similar to SSRIs and SNRIs, but it’s less likely to cause sexual problems. 

5. Nortriptyline (Pamelor)

Nortriptyline (Pamelor) is a tricyclic antidepressant (TCA) that acts on several different chemical messengers in the central nervous system, especially norepinephrine and serotonin. 

A 2006 study on nortriptyline treatment for PPD showed that it worked about as well as sertraline to relieve depression symptoms. And there’s some evidence that it may work as well as SSRIs or psychotherapy for PPD. 

But, in comparison to SSRIs, TCAs tend to cause more side effects — like dry mouth, blurred vision, and drowsiness. Because of this, they generally aren’t the first-choice treatment for depression.

6. Esketamine (Spravato)

Esketamine (Spravato) is a nasal spray that’s FDA approved for treatment-resistant depression. But it’s not approved to treat PPD. This medication isn’t recommended if you're pregnant or nursing. 

However, it may be recommended off-label for severe PPD when other options haven’t worked. Scientists are also studying this medication as a preventive treatment for PPD in mothers who show signs of depression during pregnancy. Research suggests that IV esketamine at time of birth may help prevent PPD in the following months.

Is therapy a good treatment for PPD?

Yes! Therapy is a great option for treating PPD — especially if you have mild or moderate symptoms. For many people, therapy works well, whether you do it at home or in person. Options include:

• Cognitive behavioral therapy (CBT): CBT involves speaking with a counselor or therapist about your thoughts, actions, and feelings. It’s a first-choice treatment for PPD, either on its own or with medication. People often do CBT for a couple of months. In some cases, even doing a 1-day workshop can help.

• Interpersonal therapy: This therapy focuses on how your relationships, responsibilities, and life experiences affect your mood. Just like CBT, it’s a first-choice treatment for PPD. 

• Other therapies: Many other types of therapy can help with PPD. These include non-directive counseling, peer counseling, behavioral activation therapy, and psychodynamic psychotherapy. 

You can do therapy in person or over the internet (telehealth). There are also therapy-based smartphone apps that can help. Joining a peer support group can also be a great way to connect with other people going through a similar experience. 

How long does PPD usually last?

When you have PPD, it’s hard to say how long your symptoms will last. In some people, PPD can go away on its own. But other times, symptoms can last for months or even years. In a large research study, 1 in 4 people still had symptoms 3 years after the birth. 

Having PPD can be hard on you and your baby. Without treatment, it may take longer for your symptoms to go away. That’s why it’s important to talk to a healthcare professional and get help. Getting treatment is the best thing you can do to recover from PPD and help your baby thrive. 

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Written by:

Sarah Gupta, MD

Sarah Gupta, MD, is a licensed physician with a special interest in mental health, sex and gender, eating disorders, and the human microbiome. She is currently board certified by the American Board of Psychiatry and Neurology.

Edited by:

Alex Eastman, PhD, RN

Alex Eastman, PhD, RN, is a California-based registered nurse and staff medical editor at GoodRx, where he focuses on clinical updates and Latino health.

Reviewed by:

Mandy Armitage, MD

Mandy Armitage, MD, has combined clinical medicine with her passion for education and content development for many years. She served as medical director for the health technology companies HealthLoop (now Get Well) and Doximity.

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