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 1 in every 9 people after childbirth. 

While several medications — usually antidepressants — are often used to treat PPD, only one is FDA approved for the condition. Although it can feel hard to reach out for help, treating PPD is important for you and your new baby.

Here we’ll discuss the causes of PPD, ways you might be able to prevent it, and the medications and other treatments your provider might recommend to help manage symptoms.

What is postpartum depression (PPD)?

Many people experience mood changes after giving birth, but those feelings tend to go away after a few days. 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.

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. You can read more about risk factors for PPD in our GoodRx guide to PPD.   

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. 

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. However, these medications aren’t specifically FDA approved to treat the condition. Although one medication — Zulresso — has been approved specifically for PPD, most treatments are used off-label.

If you have mild to moderate PPD, psychotherapy is usually the best first treatment. But for many people, medication can also be helpful. Here we’ll cover some specific medications that your provider might prescribe if you’re diagnosed with PPD. 

1. 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. 

They mostly work by affecting serotonin, a brain chemical that may play a role in mood. There are no FDA-approved SSRIs for PPD. But researchers have studied some SSRIs for PPD treatment, includingparoxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft). 

A 2013 study comparing sertraline to placebo (a pill with no medication in it) for PPD treatment showed significantly higher rates of response and remission — a period of no depression symptoms — in the sertraline group.

If you’re nursing, the benefits of taking an SSRI generally outweigh the risks. Sertraline is a commonly prescribed option since less of it seems to get into breast milk. But be sure to let your healthcare provider know that you’re nursing before taking any medication. You can read more about this topic in our article on pregnancy, breastfeeding, and SSRIs. 

And if you’ve had success with an SSRI treatment for depression in the past, be sure to let your provider know. They may want to start there since it’s worked for you before.

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 provider may recommend slowly lowering your dose and eventually stopping the medication. 

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

2. Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are another type of antidepressant that’s 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. 

SNRIs may be effective, but they’re usually only used if SSRIs aren’t helping or if you’ve had successful treatment with an SNRI in the past. 

There’s also evidence to suggest that venlafaxine may be a good option while nursing, although data is limited. Again, always speak to your healthcare provider before taking any medication while nursing.  

SNRIs have overlapping side effects with SSRIs, but they can cause more nausea, sleeping problems, dry mouth, and blood pressure changes. Like SSRIs, most side effects go away with time. 

3. Wellbutrin (Bupropion)

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.

Bupropion may also be a treatment option while nursing, but information is limited. As mentioned above, talk to your healthcare provider about your options if you are nursing.

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

4. Nortriptyline

Nortriptyline — a tricyclic antidepressant (TCA) — is typically used to treat depression. Nortriptyline is thought to act on several different chemical messengers in the central nervous system, but its main targets are norepinephrine and serotonin. 

A 2006 study on nortriptyline treatment for PPD showed similar improvements in depression symptoms compared to sertraline. 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.

5. Zulresso

The FDA approved Zulresso (brexanolone) in 2019. It’s the first and only medication that’s FDA approved for PPD. 

It may be an option for you if:

• You’ve been diagnosed with PPD.

• You’re at least 15 years old.

• You don’t have serious kidney disease. 

Zulresso is a human-made version of allopregnanolone, a hormone-related molecule the body normally makes from progesterone. When you’re pregnant, you have a lot of allopregnanolone in your body. But after you give birth, allopregnanolone levels go down very quickly. Zulresso restocks your body’s supply. 

Although researchers don’t know exactly how Zulresso works, replacing allopregnanolone seems to help with depression. It’s possible that it acts on the GABA system in your brain, one of the systems that’s involved in mood.

Zulresso is different from the antidepressants listed above in several ways. Here’s what you need to know:

• It’s not a pill, it’s an infusion. Zulresso isn’t a pill you take at home. It’s given by IV (intravenous) infusion over 2.5 days. This means when you have the infusion, you need to stay overnight for several days in a special treatment center.

• It takes just 3 days to work. There’s evidence that Zulresso can help some people feel better in 3 days or less. Antidepressants (like those listed above) take 1 to 2 months to fully take effect. 

• There can be barriers to accessing treatment. Zulresso costs over $30,000. Sometimes health insurance pays for Zulresso — but only if you meet certain requirements (like first trying an oral antidepressant, or giving birth fewer than 6 months prior). The company that makes Zulresso also has several financial assistance programs that can help you pay for the medication.

• You have to be monitored 24 hours a day. Zulresso can make you feel sedated and even cause you to pass out. For this reason, a healthcare provider has to monitor you 24 hours a day during the infusion. Other common side effects include dry mouth and flushing of the skin or face.

A 2018 trial that included 2 studies and over 200 people with PPD compared Zulresso to placebo. In these studies, Zulresso was more helpful than placebo in treating PPD. The evidence was good enough for the FDA to give Zulresso breakthrough-therapy status and quickly approve it for use. This means the FDA considers Zulresso to be effective and possibly even better than any other PPD treatments currently available. 

Upcoming medications

Scientists are always working on new medications for depression. The medication zuranolone may be approved soon for PPD. Just like Zulresso, zuranolone works quickly. It may also work on the GABA system in your brain. In clinical trials, taking zuranolone daily for just 2 weeks helped people with PPD get better.

Though zuranolone isn’t available yet, it might hit the market in 2023. If it’s approved, it will be the first pill available for treating PPD. It’s not clear yet whether you’ll be able to take zuranolone at home or if it will only be available at a special clinic.  

Is talk 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 just as well as medication. 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. 

Keep in mind that therapy can happen 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 your provider and get help. Getting treatment is the best thing you can do to recover from PPD and help your baby thrive. 

Why trust our experts?

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:

Sophie Vergnaud, MD

Sophie Vergnaud, MD, is the Senior Medical Director for GoodRx Health. An experienced and dedicated pulmonologist and hospitalist, she spent a decade practicing and teaching clinical medicine at academic hospitals throughout London before transitioning to a career in health education and health technology.

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