Which SSRI Antidepressants Have the Least Side Effects? 4 Options

Key takeaways:

There is no one selective serotonin reuptake inhibitor (SSRI) that is best for everyone. They all have pros and cons when it comes to side effects. For many people, SSRI side effects go away within the first few weeks.
Celexa (citalopram) and Lexapro (escitalopram) are usually well tolerated and have fewer medication interactions. But they come with a higher risk of heart rhythm problems.
Prozac (fluoxetine) and Zoloft (sertraline) may have fewer sexual side effects, but there’s not enough evidence yet to say for sure. However, they’re more likely to cause stomach problems such as nausea and diarrhea.
All SSRIs can cause a small amount of weight gain, especially if taken for more than a few months. Prozac is the least likely to cause weight gain. Paxil (paroxetine) is the most likely.

Selective serotonin reuptake inhibitors (SSRIs) are antidepressant medications that treat depression, anxiety, and other mental health conditions. They’re usually first-choice treatment options because they have fewer side effects than older types of antidepressants.

Even though SSRIs are often well tolerated, they can still cause side effects. But is there one SSRI that has the least side effects? Let’s take a look.

What are the common side effects of SSRIs?

Before we discuss which SSRI is least likely to cause side effects, you should know that all SSRIs can cause some side effects. They’re often worse when you first start the medication or after your dose is raised. But many side effects will improve or resolve on their own as you continue taking your SSRI. Talk to your healthcare team if side effects persist or are severe.

Common SSRI side effects include:

Nausea
Vomiting
Diarrhea
Headaches
Dry mouth
Sexual problems
Fatigue
Insomnia
Dizziness

Though it’s rare, SSRIs can also have serious side effects. Get medical help if you experience:

Suicidal thoughts
Changes in heart rhythm (fast heartbeat, feeling lightheaded, or fainting)
Serotonin syndrome (sweating, confusion, high fever)

What are the most commonly prescribed SSRIs?

There are several FDA-approved SSRIs available. The top five most prescribed are:

Zoloft (sertraline)
Lexapro (escitalopram)
Prozac (fluoxetine)
Celexa (citalopram)
Paxil (paroxetine)

Which SSRI antidepressants have the least side effects?

All SSRIs can cause the common side effects listed above. But some may be less likely to cause certain ones. As we’ll discuss below, some studies suggest that Celexa is one of the best tolerated SSRIs. But everyone’s experience is different. And all SSRIs are both safe and effective.

EXPERT PICKS: WHAT TO READ NEXT

More about side effects: Read more about common and rare selective serotonin reuptake inhibitor (SSRI) side effects.
Antidepressant guide: Pharmacists discuss common types of antidepressants and how they compare.
Get the facts: Physicians discuss key facts about depression and antidepressants.

Here are the pros and cons of four SSRIs that stand out from the crowd when it comes to having fewer side effects.

1. Celexa

Overall, Celexa seems to be one of the best tolerated SSRIs for many people. It tends to cause less weight gain and may have a lower risk of causing insomnia than some SSRIs. It also has fewer drug interactions, which can be helpful if you’re taking other medications.

However, compared to other SSRIs, Celexa has a higher risk of QT prolongation, a rare but potentially dangerous change to your heartbeat. This risk increases with higher doses. That's why it’s important to use the lowest effective dose of Celexa. And if you have any heart conditions, it may be best to avoid Celexa altogether.

2. Lexapro

Lexapro is closely related to Celexa. It seems to be less likely to cause nausea than some SSRIs. Like Celexa, it also has fewer medication interactions than other SSRIs.

However, some studies suggest that Lexapro might cause more headaches. And, like Celexa, it comes with a higher risk of QT prolongation, though that risk is likely lower with Lexapro than it is with Celexa.

3. Prozac

Prozac causes less weight gain than other SSRIs. Some people may even lose weight during the first few months of treatment (although they usually regain that weight over time). Prozac is also the SSRI that is least likely to cause nausea and stomach upset. There’s also some weak evidence that Prozac is less likely to cause sexual side effects. And it is less likely than other SSRIs to cause discontinuation side effects when you stop taking it.

But Prozac comes with some downsides, too. It may be more likely to cause bleeding than some SSRIs, especially for older adults. And it might cause sleep problems, such as waking up at night. Prozac can also make some people feel more anxious and restless.

4. Zoloft

For decades, Zoloft has remained one of the most commonly prescribed antidepressants. There’s some weak evidence that Zoloft, like Prozac, is less likely to cause sexual side effects. But it’s also the SSRI that’s most likely to cause diarrhea and other stomach problems. And like Prozac, it can cause sleep problems.

Do all SSRIs cause weight gain and sexual side effects?

When it comes to weight gain or sexual difficulties, keep in mind that mental health conditions can sometimes contribute to these symptoms. It can be hard to determine if your medication is the main cause. Here’s what we know about SSRIs and these two side effects:

Weight gain

Weight gain from SSRIs seems more likely to happen in people who don’t have a healthy diet, those who smoke, and those who are less active. And it seems to be a side effect that happens gradually over time. Prozac seems to cause the least amount of weight gain, while Paxil seems to cause the most weight gain.

Sexual side effects

All SSRIs can cause sexual side effects, including problems having an orgasm and erectile dysfunction. About 1 out of every 2 to 3 people who take SSRIs will have sexual side effects. Sometimes these side effects will fade over time, as your body adjusts to the medication. But the higher your SSRI dose, the more likely you are to experience sexual side effects. Though all SSRIs can cause sexual problems, Paxil has the highest risk.

How do you choose the best SSRI?

Different SSRIs will be better for different people. Each SSRI has unique pros and cons that need to be considered. Talk to your prescriber about your treatment plan and which side effects concern you most.

To help you think about your options, here’s a quick summary of the likelihood of certain side effects with different SSRIs:

SSRI	Sexual problems	Insomnia	Nausea and diarrhea	Weight gain
Prozac	Moderate	Low	Very low	None (short term) Low (long term)
Celexa	Moderate	Very low	Very low	Medium
Lexapro	Moderate	Very low	Very low	Medium
Zoloft	Moderate	Low	Low	Medium
Paxil	High	Very low	Very low	High

In addition to side effects, you and your prescriber may want to consider:

Whether you prefer a liquid or a pill
Whether you take medications that could interact with an SSRI
Whether you have heart problems or other medical conditions
Which of your symptoms are most bothersome for you
If there is an SSRI that has worked well for you (or for a parent or sibling) in the past
Whether you’re pregnant or nursing

Your prescriber will take into consideration all of this information — and more — in helping to choose the right SSRI for you. And if you want to learn more about choosing an antidepressant, check out our GoodRx Health article on the key differences between SSRIs.

Frequently asked questions

All SSRIs are generally well tolerated. But some studies suggest that Celexa seems to be better tolerated overall for people than other SSRIs. Prozac also seems to have a lower risk for many side effects.

Both Lexapro and Zoloft are safe and effective for most people. But Lexapro carries a risk for an abnormal heart rhythm called QT prolongation, while Zoloft doesn’t. However, Zoloft has more interactions to consider than Lexapro does. Your prescriber can determine which one would be a safer choice for you.

The bottom line

There is no single selective serotonin reuptake inhibitor (SSRI) that causes the least side effects. But some may be less likely than others to cause particular side effects. For example, Prozac (fluoxetine) has a lower risk of weight gain. And there’s some weak evidence that Zoloft (sertraline) and Prozac may have a lower risk of sexual side effects. Paxil (paroxetine) has a higher risk of both weight gain and sexual problems.

The best SSRI for you will depend on many factors, including which side effects you’re most concerned about. Your healthcare team can help you weigh the pros and cons of each SSRI to find the best fit for you.

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Written by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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