Sertraline vs. escitalopram: how these two SSRIs differ

It’s natural to want to know more about sertraline (Zoloft) and escitalopram (Lexapro) before starting either one. Both medications are SSRIs, a common type of antidepressant, and both have strong research behind them. 

We’ll explain how they differ, so you can share what matters most at your visit, such as other medications you take, concerns about weight gain, any heart problems, and your age.

Why both are common first choices

Sertraline (Zoloft) and escitalopram (Lexapro) are both first-line medications for depression and anxiety, which means doctors commonly try them first. Doctors often start with sertraline, which has a large evidence base and the broadest FDA approval of any SSRI. Escitalopram is a frequent second choice, and many doctors find its side effects especially mild. 

If one doesn’t turn out to be the right fit, your doctor has another strong, research-backed option to turn to. A large 2018 analysis of antidepressants found sertraline (Zoloft) and escitalopram (Lexapro) among the better options, based on how well they work and how well people handle taking them.

Sertraline and escitalopram at a glance

The clearest difference between sertraline (Zoloft) and escitalopram (Lexapro) is the list of conditions each one is approved to treat. Here’s a quick look at how the two compare.

Feature	Sertraline (Zoloft)	Escitalopram (Lexapro)
FDA-approved for major depressive disorder	Yes, adults	Yes, adults and adolescents 12 to 17
FDA-approved for generalized anxiety disorder	No	Yes, adults and children 7 and up
FDA-approved for panic disorder, PTSD, social anxiety disorder, OCD, or PMDD	Yes, approved ages vary by condition	No
Typical starting dose	25 mg a day for one week, then 50 mg	5 mg a day for one week, then 10 mg
Typical adult dose range	50 to 200 mg a day, raised in 25 to 50 mg steps	10 to 20 mg a day, raised in 5 mg steps

Which conditions each medication is approved to treat

Both medications are FDA-approved to treat depression. Beyond that, escitalopram (Lexapro) is approved for one more condition, and sertraline (Zoloft) for five more.

• Escitalopram (Lexapro) is FDA-approved for generalized anxiety disorder (GAD): An ongoing, hard-to-control worry about many different things. Sertraline (Zoloft) isn’t approved for GAD, though it’s sometimes used for it anyway, which doctors call off-label use.
• Sertraline (Zoloft) is FDA-approved for a wider range of conditions: Panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD). Escitalopram(Lexapro) isn’t approved for any of these.

If you’ve been diagnosed with GAD, panic disorder, PTSD, social anxiety disorder, OCD, or PMDD, bring it up with your doctor at your next visit. It’s one of the details they’ll want to know when choosing which medication to start you on.

Is one medication more likely to affect weight?

It’s natural to wonder about weight gain before starting an antidepressant, and it’s a fair thing to ask about. A large 2024 study in Annals of Internal Medicine gives some of the best answers so far.

• The study followed 183,118 adults at 8 U.S. health systems after they started a common antidepressant. Researchers compared each medication with sertraline (Zoloft).
• In the first six months, people taking escitalopram (Lexapro) were about 15% more likely than people taking sertraline (Zoloft) to gain 5% or more of their starting weight.
• That 15% represents the difference between the two groups. It doesn’t mean 15 out of every 100 people gained weight on escitalopram. On average, the difference between the groups was only about 0.41 kilograms, which is less than a pound.
• The study used health records and a method designed to mimic a clinical trial, so it only shows a possible link. It can’t actually prove the medication caused it.

If weight is something you’re worried about, tell your doctor.

Other medications that can matter

Millions of people take sertraline (Zoloft) and escitalopram (Lexapro) safely, and checking for medication interactions is a normal part of every visit. Still, it helps to know which ones may interact with your medication.

Tamoxifen, beta-blockers, codeine, and tramadol

Some antidepressants, including paroxetine (Paxil®), fluoxetine (Prozac®), and bupropion (Wellbutrin®), strongly slow down an enzyme called CYP2D6. Your body uses this enzyme to process medications such as tamoxifen (used to treat and prevent breast cancer), codeine, tramadol (Ultram®), and some heart and blood pressure medications called beta-blockers, such as metoprolol (Lopressor®, Toprol-XL®).

Sertraline (Zoloft) and escitalopram (Lexapro) slow it only slightly, and about the same amount at typical doses. For someone on tamoxifen, either is usually seen as a lower-risk option than the others.

Acid reflux medications

Escitalopram (Lexapro) is also affected by another enzyme, called CYP2C19. New Zealand’s medicines regulator reported that taking omeprazole (Prilosec) with escitalopram (Lexapro) increased escitalopram (Lexapro) levels in the blood by about 50%, and that some people may need a lower dose. Esomeprazole (Nexium®) works on the same enzyme and is expected to have a similar effect.

Pantoprazole (Protonix®) is generally thought to have a lower effect on CYP2C19, which is why some doctors choose it for acid reflux in patients who need both medications. Your doctor can tell you whether it’s a good option for you. If you take omeprazole or esomeprazole regularly, let your doctor know during your first visit.

What to know about heart rhythm

If heart health is a concern for you or your family, it helps to know how these two medications may affect it. In 2011, the FDA noted that high doses of citalopram (Celexa®), a related medication, can affect the heart’s rhythm. In a 2012 update, it said those findings weren’t seen with escitalopram (Lexapro).

• The effect is called QT prolongation, a change in the heart’s rhythm where the heart takes longer than usual to reset between beats. To keep that effect small, the agency set a maximum daily dose for citalopram (Celexa). It made no dosing changes for escitalopram (Lexapro).
• Escitalopram (Lexapro) can have a small effect on heart rhythm, and the effect is larger at higher doses. It’s smaller than with citalopram (Celexa) and larger than with sertraline (Zoloft).
• A review comparing SSRIs found that sertraline (Zoloft) has a low risk of QT prolongation, similar to fluoxetine (Prozac) and fluvoxamine (Luvox®), while paroxetine (Paxil) shows the lowest risk in the group.
• If you or a family member has long QT syndrome or another heart rhythm condition, or if you take another medication that affects heart rhythm, tell your doctor. A history of heart disease is one of the clearer reasons doctors may favor sertraline (Zoloft) over others.

Age and safety considerations

Escitalopram (Lexapro) is FDA-approved to treat depression from age 12 and generalized anxiety disorder from age 7. Sertraline (Zoloft) is FDA-approved for OCD in children as young as 6. We only treat adults 18 and older. If you’re looking into this for a teenager, we recommend speaking to their doctor.

Both medications carry an FDA boxed warning, the label the FDA uses for its most important safety information, about a higher risk of suicidal thoughts and behavior in children, teens, and young adults up to age 24. Doctors watch most closely in the first few months and after any dose change. If you feel worse during that time, tell your doctor, even if it seems small. 

If you or someone you know is having thoughts of suicide or self-harm, call or text the 988 Suicide and Crisis Lifeline, or chat at 988lifeline.org. In an emergency, call 911.

Does one work better than the other?

The research doesn’t show a clear winner when it comes to which one works better for depression. Most studies find that these two medications work about equally well, but a few do disagree.

• A 2018 analysis in The Lancet compared 21 antidepressants across more than 500 trials and more than 115,000 patients, the largest comparison of its kind. Both sertraline (Zoloft) and escitalopram (Lexapro) ranked among the better options for how well they work and how well people tolerate them.
• A 2007 trial that directly compared the two in 212 adults found no meaningful difference in how well they worked or how well people tolerated them over 8 weeks.
• A 2023 trial of 744 South Asian adults found a higher remission rate (few or no depression symptoms) with sertraline (Zoloft) than escitalopram (Lexapro) over 8 weeks, about 72% compared with 62%. The doses weren’t the same, with sertraline (Zoloft) given up to its maximum of 200 mg and escitalopram (LExapro) at 10 mg, so the gap may partly reflect this. On its own, it doesn’t prove sertraline (Zoloft) works better.

No strong head-to-head research shows a meaningful difference in how well these medications work for most people with depression, or with depression and anxiety together. The details in the sections above, like your diagnosis and other medications you take, usually matter more.

Side effects: what’s similar and what’s different

Side effects are often one of the biggest worries people have about starting an antidepressant, so it helps to know what’s common. Sertraline (Zoloft) and escitalopram (Lexapro) share a lot of the same side effects, but there’s less research comparing their side effects directly.

• Both can cause the side effects common to SSRIs, including nausea, sexual side effects, changes in sleep, and headaches. Nausea is most common in the first 1 to 2 weeks and often eases as your body adjusts. Not everyone gets these side effects.
• Many people describe escitalopram (Lexapro) as calm and steady and sertraline (Zoloft) as more energizing. Some find that helpful when their energy is low, while others notice jitteriness or extra anxiety at first.
• Doctors plan for that early jitteriness. When the main concern is panic disorder or social anxiety, doctors often start sertraline (Zoloft) at a lower dose, around 12.5 mg for the first week and then 25 mg, because SSRIs can briefly increase anxiety in the first week or two.
• No large, reliable study comparing both directly shows that one causes fewer sexual side effects than the other. If this is a concern for you, tell your doctor, since there are ways to manage it.

What to mention at your visit

You don’t need to walk into your appointment with all the answers. Knowing which details your doctor is most likely to consider can help you make sure they come up during your visit. 

• A diagnosis of generalized anxiety disorder (GAD), since escitalopram (Lexapro) has FDA approval for GAD and sertraline (Zoloft) doesn’t.
• A diagnosis of panic disorder, PTSD, social anxiety, OCD, or PMDD, since sertraline (Zoloft) has FDA approval for these and escitalopram doesn’t.
• Concern about weight change, since a large study linked escitalopram (Lexapro) to slightly more weight gain than sertraline (Zoloft).
• Regular use of omeprazole (Prilosec) or esomeprazole (Nexium), since they can raise the level of escitalopram (Lexapro) in your blood.
• A personal or family history of long QT syndrome or other heart rhythm problems, since the labels for both medications address it.

Taking tamoxifen or a beta-blocker isn’t on this list, but you should mention it at your visit like any other medication. Sertraline (Zoloft) and escitalopram (Lexapro) slow the enzyme that processes these medications only slightly, and about the same amount.

If you have depression and none of the factors above apply, both sertraline (Zoloft) and escitalopram (Lexapro) are well-supported first choices. Which one your doctor starts you on often depends on their clinical judgment, your personal and family history, what’s available, and your own preferences, and there’s no single correct answer. For a simpler side-by-side look, see our guide to Zoloft vs. Lexapro.

Switching between sertraline and escitalopram

Switching is common if the first medication isn’t working well for you, and your doctor will guide each step. Please don’t stop or switch on your own.

• Sertraline (Zoloft) and escitalopram (Lexapro) stay in the body for similar lengths of time, so most healthy adults can switch directly under a doctor’s care. That usually means stopping one and starting the other at a low dose. Unlike switching from an older type of antidepressant called an MAOI, there’s no required waiting period between them.
• Some people do better with a short overlap, where the doctor slowly lowers one medication while raising the other. This can help if medication changes have been hard for you in the past.
• During a switch, some people notice dizziness, irritability, flu-like feelings, or “brain zaps,” which are brief buzzing or zapping feelings in the head. These generally pass on their own and don’t necessarily mean the new medication isn’t working. Contact your doctor if symptoms are severe or don’t get better.

What each medication costs

Sertraline (Zoloft) and escitalopram (Lexapro) are both low-cost generics, and they’re typically among the more affordable medications in this class. With us, each is $19 for a 30-day supply with no insurance required, and the visit fee is $99. You can see current pricing on our sertraline prescription and escitalopram prescription pages. If you fill elsewhere, check the price with your pharmacy.