Lexapro vs. Zoloft: differences and similarities

Antidepressants are being used more and more as rates of depression rise. But with so many on the market, it can be tough to understand the differences between them. Lexapro and Zoloft belong to the same class of prescription antidepressant medications, but they also differ in several ways—read on to learn how they compare. 

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Lexapro (escitalopram) and Zoloft (sertraline) are both prescription antidepressants that can help improve your depression. It’s estimated that 12% of people will develop depression at some point in their lifetimes. Depression is the second most common cause of disability among adults in the U.S., and the symptoms of depression can affect your day-to-day life (Rush, 2020). 

As depression has become more prevalent, so has the use of prescription antidepressants. Over 13% of adults in the U.S. have taken antidepressants in the past 30 days (Brody, 2020).

The most common type of prescription treatment of depression is the selective serotonin reuptake inhibitors or SSRI drug class—both Lexapro and Zoloft are SSRIs (Chu, 2021). These drugs improve depression symptoms by increasing serotonin levels; serotonin plays a key role in regulating your mood. Other SSRIs include fluoxetine (brand name Prozac), paroxetine (brand name Paxil, Brisdelle), and citalopram (brand name Celexa). 

If you and your healthcare provider decide to try Lexapro or Zoloft, it is helpful to know how they compare.

Lexapro is the brand name of the generic drug escitalopram oxalate. It is FDA-approved to treat both major depressive disorder (MDD) and generalized anxiety disorder (GAD). Still, healthcare professionals may use it off-label to treat obsessive-compulsive disorder (OCD) and other disorders. “Off-label” means that providers use the drug to treat conditions other than the ones approved by the FDA (FDA, 2017; UptoDate, n.d.-a). 

Zoloft is the brand name for sertraline hydrochloride and is also FDA-approved to treat MDD. However, unlike Lexapro, it’s also approved for obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD) (FDA, 2016). Providers may also use it off-label to treat premature ejaculation, GAD, and other conditions (UpToDate, n.d.-b).

While both Lexapro and Zoloft treat major depression, there are some differences in the other FDA-approved and off-label uses for these medicines.

Lexapro uses

FDA-approved uses include (FDA, 2017):

• Major depressive disorder (MDD) in adults and adolescents over age 12 (short-term and long-term treatment)

• Generalized anxiety disorder (GAD) in adults (short-term treatment)

Off-label (not FDA-approved) uses include (UptoDate, n.d.-a):

• Obsessive-compulsive disorder (OCD)

• Panic disorder

• Post-traumatic stress disorder (PTSD)

• Binge eating disorder

• Body dysmorphic disorder

• Bulimia nervosa

• Premature ejaculation

Zoloft uses

FDA-approved uses include (FDA, 2017):

• Major depressive disorder (MDD)

• Obsessive-compulsive disorder (OCD)

• Panic disorder (PD)

• Post-traumatic stress disorder (PTSD)

• Social anxiety disorder (SAD)

• Premenstrual dysphoric disorder (PMDD)

Off-label (not FDA-approved uses (UptoDate, n.d.-b):

• Generalized anxiety disorder

• Premature ejaculation

• Binge eating disorder

• Body dysmorphic disorder

• Bulimia nervosa

While rare, children, adolescents, and young adults are at an increased risk of worsening depression symptoms and suicidal thoughts while taking SSRI antidepressants. The FDA has issued a black box warning regarding this potential risk. Watch out for any changes in behavior or mental health, including worsening depression, panic attacks, and suicidal thoughts, when starting either medication or changing its dose (FDA, 2018).

Sexual side effects

Sexual dysfunction is a common side effect of all SSRI antidepressant medications, though the frequency differs among the individual drugs and can be as high as 80% in some studies (Hirsch, 2019). For most SSRIs, the risk of side effects increases as you go up in dose. 

Lexapro and Zoloft may cause ejaculation disorder (delayed ejaculation), lowered sex drive, and impotence (erectile dysfunction) in men. These prescription drugs may lower libido in women, but people only reported an inability to orgasm with Lexapro (FDA, 2017; FDA, 2016).

If you experience sexual side effects on either of these medications, bring it up with your healthcare provider. Other antidepressants, like bupropion, mirtazapine, and serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine (brand name Cymbalta) and venlafaxine (brand name Effexor) may be better options for you. 

But if your condition only seems to respond to SSRIs, adding bupropion (brand name Wellbutrin) may help decrease your sexual side effects (Jing, 2016).

Withdrawal symptoms

Both Zoloft and Lexapro may cause side effects if you stop taking them too quickly. Withdrawal or discontinuation symptoms from either medication may include nausea, nightmares, dizziness, vomiting, irritability, headache, and paresthesias (prickling, tingling sensation on the skin) (Hirsch, 2020).

Work with your healthcare provider to slowly reduce your dose of these medications to avoid these adverse effects. SSRI withdrawal symptoms typically begin within one week of discontinuing the drug and clear up within three weeks (Hirsch, 2020).

Zoloft side effects

All drugs have side effects, some common and others occurring less frequently. Some of the most common Zoloft side effects include (FDA, 2016):

• Nausea

• Diarrhea

• Insomnia 

• Dry mouth

• Fatigue 

• Dizziness

• Sleepiness 

• Agitation 

• Ejaculation failure 

• Loss of appetite

• Upset stomach

Overall, these side effects made 12% of the patients studied quit taking their medication. The most common reasons people report stopping the drug were nausea, diarrhea, agitation, and insomnia (FDA, 2016).

Lexapro side effects

The extent to which you have side effects on Lexapro may depend on the dose you’re prescribed. Common side effects were dose-dependent in clinical trials, meaning more people experienced them on 20 mg than 10 mg. Some of the most common Lexapro side effects include (FDA, 2017): 

• Nausea

• Trouble sleeping

• Ejaculation disorder (delayed ejaculation) 

• Diarrhea 

• Sleepiness 

• Dry mouth

• Increase in sweating

• Dizziness

• Flu-like symptoms

• Fatigue 

In clinical trials, 6–8% of people taking Lexapro stopped the medicine because of the side effects. As mentioned, the side effects of escitalopram are dose-dependent; studies have found higher adverse effects with higher daily doses. This showed in the discontinuation rates, as more people on 20 mg stopped taking Lexapro than those on 10 mg (FDA, 2017). 

It’s important to tell your healthcare provider about all the medications and supplements you’re taking, no matter which of these antidepressants you use, because of potential drug interactions. 

One of the most serious drug interactions with any SSRI is serotonin syndrome, which happens when too much serotonin builds up in the body. This can happen due to medications boosting serotonin levels directly or interfering with how your body breaks down this neurochemical. Serotonin syndrome may cause shivering, high blood pressure, elevated heart rate, fever, diarrhea, or may cause seizures and can be life-threatening (Simon, 2021). 

Escitalopram and sertraline both increase levels of serotonin in the body. For that reason, you should not take either of these medications with other drugs that do the same thing, including tricyclic antidepressants (like amitriptyline), fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and even over-the-counter supplements containing St. John's Wort (Simon, 2021).

Lexapro and Zoloft should also not be taken with medications that affect how your body metabolizes serotonin, especially monoamine oxidase inhibitors (MAOIs) such as phenelzine, selegiline, rasagiline, and tranylcypromine. Combining these medications increases your risk of serotonin syndrome (Simon, 2021).

You may be at an increased risk of bleeding if you take Zoloft or Lexapro with any blood-thinning medications. This includes prescription blood thinners such as warfarin (brand name Coumadin) to over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen. 

You should not use either medication with pimozide, an antipsychotic medicine, because the combination increases the risk of developing problems with your heart rhythm (arrhythmias) (FDA, 2016; FDA, 2017).

Both Zoloft and Lexapro may cause drowsiness, either directly or by interfering with your quality of sleep. They can also affect your ability to think, react quickly, or make decisions—alcohol also has these effects. Though alcohol has not been shown to worsen these effects, it’s still standard medical advice to avoid drinking when taking either of these medications (FDA, 2016; FDA, 2017).

This list does not include all of the possible drug interactions with Zoloft or Lexapro—talk to your healthcare provider or pharmacist if you have any questions.

There’s a lot of information out there about the differences and similarities between Zoloft and Lexapro. Here is a summary of some of the characteristics of these two SSRIs medications:

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How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

June 23, 2021

Written by

Linnea Zielinski

Fact checked by

Chimene Richa, MD

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About the medical reviewer

Chimene Richa, MD

Dr. Richa is a board-certified Ophthalmologist and medical writer for Ro.