Zoloft vs. Lexapro for Depression: 5 Key Differences, from Dosages to Side Effects

Mental healthcare should always be a priority — no matter your background, race, or gender. So if you’ve experienced symptoms of depression, know that you’re not alone. These feelings of sadness can be discouraging, but many treatment options are available when you’re ready to pursue them.

Zoloft (sertraline) and Lexapro (escitalopram) are two common, prescription-only medications for treating depression. They belong to the same group of antidepressants: selective serotonin reuptake inhibitors (SSRIs). They’re thought to work by raising the amount of serotonin in your brain.

Zoloft and Lexapro are both first-choice medications for treating depression. But they have some minor differences to be aware of. Below, read about five things to keep in mind when considering Zoloft versus Lexapro for depression.

1. Zoloft has more FDA-approved uses than Lexapro

Zoloft and Lexapro are both FDA approved to treat depression. But the age groups they treat differ somewhat. Zoloft is primarily approved for adults, while Lexapro can be used to treat depression in people ages 12 and older.

Age aside, Zoloft is approved to treat more mental health conditions than Lexapro. In addition to depression, Zoloft is approved to treat:

• Obsessive-compulsive disorder (OCD) in adults and kids ages 6 and older

• Panic disorder in adults

• Post-traumatic stress disorder (PTSD) in adults

• Social anxiety disorder in adults

• Premenstrual dysphoric disorder (PMDD) in adults

By comparison, Lexapro’s only additional approved use is treating generalized anxiety disorder. In practice, though, Lexapro is prescribed off-label for many of the same conditions Zoloft is approved for.

2. Zoloft and Lexapro come in different dosage forms and have different recommended dosages

Zoloft and Lexapro are both oral medications. But their dosage forms and recommended dosages are slightly different.

Dosage forms

Zoloft comes as 25 mg, 50 mg, and 100 mg tablets. A generic version of Zoloft also comes as 150 mg and 200 mg capsules. If you want or need an option other than pills, Zoloft also comes as a 20 mg/mL liquid solution.

EXPERT PICKS: WHAT TO READ NEXT

• Sertraline (Zoloft) stories: Hear from real people about their experiences taking Zoloft.

• Mechanism of action: Learn from pharmacists about how selective serotonin reuptake inhibitors (SSRIs) work to manage mental health conditions.

• How SSRIs compare: See how Zoloft and Lexapro stack up to other SSRIs.

Lexapro is available as 5 mg, 10 mg, and 20 mg tablets. The generic version also comes as a 5 mg/5 mL liquid solution.

Good to know: Zoloft oral solution is very concentrated (strong). It must be mixed with 4 oz of water, lemonade, or orange juice before you take it. Ginger ale and lemon-lime soda are also acceptable options. Your pharmacist can help answer questions about diluting the oral solution.

Recommended dosages

Zoloft and Lexapro are both taken once a day, with or without food. They can typically be taken in the morning or evening. But whatever time you choose to take your medication, be consistent.

Zoloft’s usual starting dosage is 50 mg per day for depression in adults. The maximum recommended dosage is 200 mg per day.

Lexapro’s starting dosage is usually 10 mg per day for depression in adults and adolescents. The maximum recommended dosage is 20 mg per day.

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3. Zoloft and Lexapro are both effective, but there’s conflicting data on if one is better than the other

Studies suggest that SSRIs like Zoloft and Lexapro are more effective at treating depression than a placebo (a pill with no medication in it). But results from studies comparing these two medications are mixed. For instance:

• One meta-analysis found that Lexapro was more effective than other SSRIs, including Zoloft, at treating depression.

• A different study found that Zoloft was more effective than Lexapro.

• Another study showed that Zoloft and Lexapro were similarly effective.

At the end of the day, Zoloft and Lexapro are both considered first-choice medication options for treating depression. And there's no clear winner between the two. Your healthcare professional will work with you to find the option that's most effective for you.

Also, remember: SSRIs can take several weeks to work. During this time, you may not notice a big difference in your symptoms. It could take up to 8 weeks to see the full benefits. In the meantime, a healthcare professional may recommend cognitive behavioral therapy (CBT) in addition to medication to help treat your symptoms. This can be helpful while the medication starts working.

4. Zoloft and Lexapro have slightly different side effects

Zoloft and Lexapro are usually well tolerated. They share similar side effects, but there are some differences to keep in mind. For instance, they can both cause erectile dysfunction. But Zoloft may be more likely to cause nausea, diarrhea, and trouble sleeping than Lexapro. Other differences in common side effects can be seen in the chart below.

Shared serious side effects

All SSRIs carry a boxed warning — the FDA’s most serious type of medication warning — about a higher risk of suicidal thoughts and behaviors in children, adolescents, and young adults. Contact a healthcare professional right away if you experience sudden changes in behavior or thoughts of self harm while taking an SSRI. These risks are generally highest during the first few months of taking an SSRI.

Although rare, Zoloft and Lexapro can cause other serious side effects, including:

• Serotonin syndrome

• Discontinuation syndrome, which is also known as antidepressant withdrawal

• Bruising or bleeding

• Seizures

• Low sodium levels

• Glaucoma complications

• Manic episodes in people with bipolar disorder

If you or a loved one experience any of these side effects, make sure to reach out to a healthcare professional immediately.

Good to know: Zoloft and Lexapro are both good options for treating depression in older adults. This is because they have less side effects than other types of antidepressants, such as tricyclic antidepressants.

5. Lexapro generally has fewer drug interactions

Like most medications, Zoloft and Lexapro have possible drug interactions to be aware of. But Lexapro generally has fewer drug interactions than Zoloft. It’s not as likely to block certain liver enzymes (proteins) that are responsible for breaking down medications in your body. If you’re trying to decide between the two SSRIs, this may factor into your decision — especially if you’re taking other medications known to interact with Zoloft.

Zoloft interactions

Zoloft blocks an enzyme called CYP2D6. This enzyme is in charge of metabolizing several medications. If it can’t work efficiently, these medications can build up in the body. This may lead to added side effects.

Notable medications that can interact with Zoloft in this way include:

• Risperidone (Risperdal)

• Flecainide

• Tolterodine (Detrol)

• Metoprolol (Toprol XL)

• Atomoxetine (Strattera)

• Venlafaxine (Effexor XR)

Shared interactions

These medications can interact with both Zoloft and Lexapro:

• Monoamine oxidase inhibitors (MAOIs), such as selegiline (Zelapar)

• Other medications that raise serotonin levels, such as triptans, tramadol (ConZip), and other SSRIs

• Medications that raise the risk of bleeding, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and blood thinners

• St. John’s wort, an herbal supplement

• Pimozide

• Certain antipsychotics, such as thioridazine

• Certain heart rhythm medications, such as propafenone

Good to know: Make sure your prescriber and pharmacist have an updated list of all over-the-counter and prescription medications you take. They can check to see if there are potential interactions with your SSRI.

How to save on Zoloft and Lexapro

Zoloft and Lexapro are relatively affordable, especially the generic versions. But there are ways to save on both of them, even if you don’t have insurance coverage:

• Zoloft: You may be able to fill a 1-month supply of sertraline 50 mg tablets for as low as $9.42 at certain pharmacies with a free GoodRx coupon. If you qualify, you may also be able to pay as little as $10 per month for the generic capsules or $4 per month for brand-name Zoloft using a manufacturer savings card.

• Lexapro: You may be able to fill a 1-month supply of escitalopram 10 mg tablets for as low as $8.64 at certain pharmacies with a free GoodRx coupon.

Why trust our experts?

Written by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at 1-800-662-4357. For immediate assistance, call the National Suicide Prevention Lifeline at 988, or text “HOME” to 741-741 to reach the Crisis Text Line.