What is better tolerated, Zoloft or Lexapro?

October 10, 2025 •

4 min read

According to one clinical analysis, Lexapro may be considered more effective and acceptable than some other SSRIs, but the question of what is better tolerated, Zoloft or Lexapro, has a more complex answer that depends heavily on the individual's specific side effect sensitivities. The choice between the two often comes down to weighing different side effect profiles, specific condition being treated, and individual response.

Quick Summary

This article compares the tolerability of the SSRIs Zoloft (sertraline) and Lexapro (escitalopram). It examines their side effect profiles, including differences in gastrointestinal upset and sexual dysfunction, and discusses factors like FDA approvals, dosing, drug interactions, and discontinuation syndrome. Individual patient response and specific conditions are key considerations in determining the better-tolerated option.

Key Points

Gastrointestinal Side Effects: Zoloft (sertraline) is generally associated with a higher frequency of initial GI side effects like nausea and diarrhea compared to Lexapro (escitalopram).
Sexual Side Effects: Lexapro may cause a higher rate of ejaculatory delay in men, though both medications can affect sexual function.
Overall Tolerability and Discontinuation: Conflicting data suggests Lexapro may have better overall acceptability for some, but also higher rates of discontinuation due to intolerable side effects in certain studies.
Specific Indications: Zoloft is FDA-approved for a broader range of conditions, including OCD and PTSD, while Lexapro is approved for MDD and GAD.
Individual Response is Key: An individual's unique response to the medication is the most important factor in determining which is better tolerated, often requiring a trial-and-error process under medical supervision.
Drug Interactions: Lexapro typically has fewer drug interactions compared to Zoloft, which can be an important consideration for people on multiple medications.
Older Adults: Some evidence suggests Lexapro may be better tolerated in older adults new to SSRIs.

Zoloft (sertraline) and Lexapro (escitalopram) are both selective serotonin reuptake inhibitors (SSRIs), a class of antidepressant medications used to treat mental health conditions by increasing serotonin levels in the brain. While they share a similar mechanism of action and overall effectiveness in treating major depressive disorder, their differences in side effect profiles and overall tolerability are important considerations when choosing a treatment. This comparison examines these distinctions, relying on clinical data and patient experience to provide a balanced overview.

Side Effect Frequency and Type

While Lexapro is sometimes cited for its generally high acceptability, Zoloft is known to have a higher frequency of overall side effects, particularly gastrointestinal (GI) issues. This is especially notable at the beginning of treatment. For example, clinical trials have shown that:

Nausea is reported by 26% of Zoloft users versus 15% of Lexapro users.
Diarrhea is reported by 20% of Zoloft users compared to 8% of Lexapro users.

For individuals with sensitive stomachs or pre-existing GI conditions like irritable bowel syndrome (IBS), the lower rate of GI side effects may make Lexapro a more tolerable option. However, Lexapro is associated with other side effects that may impact tolerability. For example, sexual side effects vary between the two. In clinical trials, delayed ejaculation was reported more frequently with Lexapro (12% of men) than Zoloft (8% of men). Both can also cause decreased libido and difficulty with orgasm in both men and women.

Discontinuation Rates and Overall Tolerability

Discontinuation rates offer another lens through which to view tolerability, as they reflect how many patients stop taking a medication due to adverse effects. Conflicting data exists on this front, highlighting the individualized nature of treatment. One study found that Lexapro may have a higher rate of intolerable side effects, causing 6% of users to stop treatment, compared to 2-3% of Zoloft users. However, other studies have suggested that Lexapro may have slightly higher patient adherence rates and fewer overall dosage adjustments in real-world observations. These differences may be influenced by the specific condition being treated, dosing strategy, and individual patient sensitivity.

Broader Differences in Usage and Patient Profiles

The most appropriate medication for a patient depends on more than just general tolerability. The FDA-approved indications for each drug are a major differentiating factor, influencing which one a doctor will prescribe based on a patient's specific diagnosis.

Zoloft vs. Lexapro Comparison


Feature	Lexapro (Escitalopram)	Zoloft (Sertraline)
FDA-Approved Uses	Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD)	MDD, Obsessive-Compulsive Disorder (OCD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Anxiety Disorder (SAD), Premenstrual Dysphoric Disorder (PMDD)
Common GI Side Effects	Fewer gastrointestinal side effects like nausea and diarrhea reported initially.	More frequent gastrointestinal side effects, especially nausea and diarrhea.
Onset of Action	Some evidence suggests a slightly faster onset of action.	Takes the standard 4-6 weeks for full effect, sometimes longer.
Sexual Side Effects	Higher rate of ejaculatory delay reported in clinical trials.	Lower rate of ejaculatory delay reported in clinical trials.
Drug Interactions	Fewer known drug interactions due to more selective metabolism.	More potential drug interactions due to broader metabolic impact.
Dosing Flexibility	Simpler dosing structure, typically 10-20 mg daily.	Greater dosing flexibility, up to 200 mg daily.
Use in Special Populations	May be better tolerated in older adults and new SSRI users.	More extensive data available for pregnancy and lactation.

What This Means for Your Treatment

Deciding which medication is better tolerated is highly personal and should be done in consultation with a healthcare provider. Here are some key takeaways:

For GAD: Lexapro has a specific FDA approval for GAD and is often chosen first for generalized anxiety due to its sometimes smoother onset and fewer initial GI side effects.
For multiple conditions: If a person has co-occurring conditions like OCD or PTSD alongside depression or anxiety, Zoloft's broader FDA-approved indications may make it a more versatile choice.
For sensitive GI systems: Individuals prone to nausea or diarrhea may find Lexapro more tolerable, though this is not guaranteed.
For older adults and new users: Some evidence suggests Lexapro is better tolerated for these groups, potentially due to its more targeted action and simpler dosing.
Trial and error: It is common for individuals to try several medications before finding the one that provides the best balance of effectiveness and tolerable side effects. What works perfectly for one person may not be the ideal choice for another.

Conclusion

There is no single answer to whether Zoloft or Lexapro is universally better tolerated, as the optimal choice depends on an individual's unique biology, specific diagnosis, and sensitivity to side effects. While Zoloft may cause more frequent GI upset, Lexapro might carry a higher risk of intolerable side effects for some, such as specific sexual side effects. These medications are generally considered first-line options for depression and anxiety, and a healthcare provider's guidance is essential for finding the right treatment. Close monitoring of symptoms, especially during the initial weeks and with any dose changes, is critical to ensuring the best therapeutic outcome.

For more information on the safety and usage of these medications, consult the U.S. Food and Drug Administration (FDA).

Frequently Asked Questions

Lexapro has specific FDA approval for Generalized Anxiety Disorder (GAD) and is often favored for its potentially smoother onset and fewer initial GI side effects. Zoloft is approved for a broader range of anxiety-related conditions, including Panic Disorder and Social Anxiety Disorder, making it a good choice if multiple anxiety conditions are present.

Zoloft is more likely to cause nausea and other gastrointestinal issues like diarrhea compared to Lexapro, especially during the first few weeks of treatment.

Yes, but any switch between these medications should be done under the supervision of a healthcare provider. A process called 'cross-tapering' is often used to gradually reduce the dose of one medication while introducing the other to minimize side effects and withdrawal symptoms.

Real-world data has suggested that Lexapro may be associated with slightly more weight gain than Zoloft over a six-month period, but weight changes vary significantly by individual and neither is definitively linked to dramatic weight gain.

Yes, both Lexapro and Zoloft, like all antidepressants, carry an FDA black box warning for an increased risk of suicidal thoughts and behaviors in young adults (up to age 24).

Some evidence suggests that Lexapro is better tolerated, particularly in older adults and those new to SSRIs. However, individual patient response and overall health profile are key factors for a healthcare provider to consider.

Lexapro generally has fewer drug interactions because it is less likely to affect certain liver enzymes involved in drug metabolism compared to Zoloft.

If stopped abruptly, both can cause discontinuation syndrome with symptoms such as anxiety, dizziness, fatigue, irritability, and "brain zaps." Tapering off the medication gradually under a doctor's guidance is crucial to prevent this.

While Lexapro may show slightly faster effects for some, both medications typically take 4-6 weeks for the full therapeutic benefits to be felt.