Lexapro vs. Zoloft: Which is best for me?

A quick overview of Lexapro vs. Zoloft

Lexapro (escitalopram) and Zoloft (sertraline) are both selective serotonin reuptake inhibitors (SSRIs). SSRIs work by increasing the amount of serotonin available in your brain, a chemical that helps regulate mood, sleep, and anxiety.

Despite both being SSRIs, these two medications aren’t exactly the same. They have different active ingredients, are FDA-approved for slightly different uses, and can come with different side effects.

Lexapro vs. Zoloft: A side-by-side comparison

This table breaks down the main differences between Lexapro and Zoloft to help you understand how each medication might fit your specific situation.

What is Lexapro used for?

Lexapro is FDA-approved for depression and generalized anxiety disorder. It’s also frequently prescribed off-label for social anxiety, panic disorder, and obsessive-compulsive disorder (OCD).

“I like Lexapro as a good place to start because it’s one of the better tolerated SSRIs, so it has a higher likelihood of being a good fit,” explains Kate Hanselman, PMHNP, VP of clinical psychiatry at Thriveworks. “It’s especially helpful for those with mostly generalized anxiety symptoms.”

What is Zoloft used for?

Zoloft is FDA-approved to treat a number of mental health conditions. They include depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD). It’s also sometimes prescribed off-label for generalized anxiety disorder.

That flexibility makes Zoloft a good choice for people managing multiple mental health conditions.

Hanselman takes a patient-history-first approach with Zoloft: “If someone has had excellent outcomes with Zoloft before, it’s a good place to start since it’s familiar.” And since Zoloft has a larger dosage range, that can also be helpful for someone who may want to titrate up slowly, she says.

FDA-approved uses: Lexapro vs. Zoloft

Is Lexapro or Zoloft better for anxiety?

There’s no single winner. Both medications are effective for anxiety, but the type of anxiety can affect medication choice. Lexapro is FDA-approved specifically for GAD and is considered a first-choice medication for GAD in people who are not managing another mental health condition. Zoloft, on the other hand, is FDA-approved for social anxiety disorder and panic disorder.

“Neither is empirically better or worse, it’s really dependent on tolerability and efficacy for that particular person,” Hanselman says.

Keep in mind, medication is just one option for treating anxiety. Therapy, especially cognitive behavioral therapy (CBT), is also commonly recommended for anxiety disorders and may be used alone or alongside medication. CBT helps people recognize anxiety patterns, practice coping strategies, and gradually change behaviors that make their anxiety worse. The most effective anxiety treatment plan really depends on the person and may include factors like: symptom severity, personal preference, access to therapy, and overall medical history.

Is Lexapro or Zoloft better for depression?

For treating depression alone, they’re both solid options. A large 2018 meta-analysis in The Lancet found that both were effective for depression and more people stayed on them compared to some other antidepressant options.

Where the decision gets more nuanced is if depression exists alongside another mental health condition, like PTSD, OCD, panic disorder, or PMDD. In these cases, Zoloft may be able to treat multiple conditions with just one medication.

Side effects of Lexapro vs. Zoloft

Because Lexapro and Zoloft are both SSRIs, they tend to come with similar side effects. But in clinical trials for the medications, the rates of side effects were often higher with Zoloft.

Sources: FDA prescribing information for escitalopram (2017) and sertraline (2016). Lexapro data based on clinical trials of 715 patients with MDD; Zoloft data based on all clinical trials of 3,066 patients.

Zoloft is more likely to cause GI issues like diarrhea, especially in the first few weeks. It may also be more likely to cause insomnia. Fatigue or drowsiness can happen with either medication, especially early in treatment. These side effects usually get better over time as your body adjusts to the medication.

Sexual side effects (like reduced libido and difficulty reaching orgasm), are possible with both medications and are one of the most frequent reasons patients ask about switching. If this is affecting you, talk to your provider. They may recommend a different dosage or a different medication altogether.

Hanselman’s clinical experience tracks with what the research shows: “I’ve seen Lexapro be very well tolerated, while Zoloft can be titrated more slowly but often has more initial side effects including nausea, diarrhea, headache. They usually get better within the first week.”

Practical considerations when choosing between Lexapro and Zoloft

There are a number of considerations that go into the decision between Lexapro and Zoloft. They include:

• Your symptoms: What is the main diagnosis? Are there other mental health conditions you are managing that Zoloft may be able to treat?
• Previous medications: What have you tried before? If you’ve tried one SSRI and it didn’t work or caused bothersome side effects, that information helps narrow the choices.
• Side effect priorities: Everyone has different concerns. If potential side effects are a concern, a provider might recommend Lexapro.
• Age: Lexapro is FDA-approved for depression in adolescents 12 and older and for GAD in children 7 and older. Zoloft is approved for OCD in children as young as 6.

How to switch between Lexapro and Zoloft

Switching between these two SSRIs is pretty straightforward but should always be done under the guidance of a provider. That typically looks like gradually reducing one medication while slowly introducing the other. This minimizes discomfort and avoids a gap in treatment. Mild side effects during the transition are normal, and it may take four to six weeks before you feel the full benefit of the new medication.

Never try to stop or switch your medication on your own. Stopping an SSRI abruptly can cause antidepressant discontinuation syndrome, which can come with symptoms like dizziness, irritability, nausea, and brain zaps that result from your brain adjusting to the change. And taking too much of either medication increases the risk of serotonin syndrome, a rare but serious condition caused by too much serotonin activity in the brain.

Talking with a provider can help you find the right fit

Finding the right antidepressant can sometimes require a little trial and error, since individual brain chemistry, genetics, and life circumstances all influence how a medication works in your body.

If your current medication isn’t working well enough or is causing side effects that affect your quality of life, bring that information to your next appointment. Specific details help your provider make better decisions about your treatment plan.

Here are a few questions worth asking your provider:

• Why was this medication chosen over others for my specific situation?
• What side effects should I watch for, and when should I report them?
• How long should I wait before we consider switching?
• Are there any interactions with my other medications or supplements?
• What would the process look like if we decide to try something else?

Frequently asked questions (FAQs)

What is the difference between Lexapro and Zoloft?

Both are SSRIs that treat depression and anxiety, but they differ in their FDA approvals, side effect profiles, and who they tend to work best for. Zoloft is approved for OCD, PTSD, panic disorder, social anxiety, and PMDD. Lexapro is specifically approved for depression and GAD.

Is Lexapro stronger than Zoloft?

The two are generally thought to be equally effective at treating depression. What matters more than “stronger” is which medication is the better fit for your specific symptoms and circumstances.

Can you take Lexapro and Zoloft together?

No. Taking two SSRIs simultaneously increases the risk of serotonin syndrome, a rare but serious condition caused by too much serotonin activity. If you’re switching between the two, your provider will guide you through how to do so safely.

Does Lexapro or Zoloft cause more weight gain?

Both can cause modest weight changes, but neither is strongly associated with significant weight gain. It varies by person and tends to be more noticeable with longer-term use.

Which has fewer side effects, Lexapro or Zoloft?

They share most of the same side effects, but Zoloft is more likely to cause GI issues like nausea and diarrhea. Fatigue or drowsiness can happen with either medication, especially early on. Sexual side effects can happen with both.

How long does it take for Lexapro or Zoloft to work?

Most people notice some improvement within two to four weeks, but the full benefit typically takes four to six weeks. Give the medication time before deciding it isn’t working, and talk to your provider before making any changes.

Is Zoloft or Lexapro better for social anxiety?

Zoloft is FDA approved for social anxiety disorder and is considered a first-choice option. Lexapro is sometimes used off-label for social anxiety.