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Home/Treatments/Compare/Lexapro vs Zoloft
Treatment Comparison
SSRI

Lexapro vs Zoloft: Differences, Similarities & Which Is Better

Compare Lexapro (escitalopram) and Zoloft (sertraline) - two commonly prescribed SSRIs for depression and anxiety. Learn about effectiveness, side effects, dosing, and which might be right for you.

Bottom Line

Both Lexapro and Zoloft are effective SSRIs for treating depression and anxiety. Lexapro is often considered slightly better tolerated with fewer drug interactions, while Zoloft has a broader FDA-approved indication list and more flexibility in dosing.

Lexapro
(escitalopram)
Zoloft
(sertraline)

Side-by-Side Comparison

FeatureLexapro (escitalopram)Zoloft (sertraline)
Drug ClassSSRISSRI
FDA-Approved ForMajor depression, Generalized anxiety disorderMajor depression, OCD, Panic disorder, PTSD, Social anxiety, PMDD
Typical Starting Dose10 mg once daily50 mg once daily
Usual Effective Dose10-20 mg/day50-200 mg/day
Time to Effect2-4 weeks2-4 weeks
Half-Life27-32 hours26 hours
Drug InteractionsFewer (minimal CYP450 inhibition)More (moderate CYP2D6 inhibition)
Weight EffectsWeight neutral to slight gainWeight neutral to slight loss initially
Sexual Side EffectsCommon (similar to other SSRIs)Common (similar to other SSRIs)
GI Side EffectsLess commonMore common (diarrhea, nausea)
Approved for Children12+ years (depression)6+ years (OCD)
Pregnancy CategoryUse with cautionPreferred SSRI in pregnancy
Generic AvailableYesYes

Lexapro vs Zoloft: Overview

Lexapro (escitalopram) and Zoloft (sertraline) are both selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants. Both work by increasing serotonin levels in the brain, improving mood, reducing anxiety, and helping regulate sleep and appetite. While they share the same mechanism, there are important differences in their side effect profiles, drug interactions, and FDA-approved uses.

Which Is More Effective?

Clinical studies show both medications are similarly effective for treating depression and anxiety. A large meta-analysis found escitalopram (Lexapro) had a slight edge in efficacy among SSRIs, but the difference is small. In practice, individual response varies significantly - some patients do better on one than the other. If one doesn't work well, switching to the other is a reasonable approach.

Side Effects Comparison

Both medications share common SSRI side effects including nausea, headache, insomnia, sexual dysfunction, and drowsiness. However, there are notable differences:

Lexapro tends to have

  • Lower rates of GI upset (nausea, diarrhea)
  • Potentially more weight gain over time
  • Fewer drug interactions

Zoloft tends to have

  • Higher rates of diarrhea and GI symptoms
  • More activating/energizing initially
  • Slightly more drug interactions due to CYP2D6 effects

Drug Interactions

Lexapro has fewer drug interactions because it has minimal effects on cytochrome P450 enzymes. Zoloft moderately inhibits CYP2D6, which can affect levels of other medications including some beta-blockers, antipsychotics, and pain medications. Both interact dangerously with MAOIs and should not be combined with other serotonergic drugs without medical supervision (risk of serotonin syndrome).

Special Populations

Pregnancy & Breastfeeding

Zoloft is generally considered the preferred SSRI during pregnancy due to more safety data. Both pass into breast milk but are generally considered compatible with breastfeeding.

Children & Adolescents

Zoloft is FDA-approved for OCD in children 6+ and is commonly used off-label for pediatric depression and anxiety. Lexapro is approved for depression in adolescents 12+.

Elderly

Both are used in older adults. Lower starting doses are recommended. Watch for hyponatremia (low sodium) with either medication.

Switching Between Lexapro and Zoloft

If one SSRI isn't working well or causes intolerable side effects, switching to another is common practice. Your doctor may do a direct switch (stopping one and starting the other) or a cross-taper (gradually reducing one while starting the other). Never stop an antidepressant abruptly without medical guidance.

Cost Comparison

Both medications are available as generics and are similarly affordable. Generic escitalopram and sertraline typically cost $4-$30/month depending on pharmacy and insurance. Brand-name versions are significantly more expensive and rarely necessary.

Which Should You Choose?

There's no universally "better" choice - it depends on your specific situation:

Lexapro
You want fewer drug interactions, are sensitive to GI side effects, or prefer once-daily simplicity
Zoloft
You're pregnant or planning pregnancy, need treatment for OCD/PTSD/panic, or prefer more dosing flexibility
Either
You have uncomplicated depression or GAD with no strong preference factors

Frequently Asked Questions

Related Comparisons

Prozac Vs ZoloftLexapro Vs ProzacLexapro Vs WellbutrinZoloft Vs Paxil

Medical Disclaimer: This comparison is for informational purposes only and does not constitute medical advice. Always consult with a healthcare provider before starting, stopping, or changing any medication.

Last reviewed: 2025-01-02 by HeyPsych Medical Review Board