Zoloft vs Lexapro Side Effects
Zoloft (sertraline) and Lexapro (escitalopram) are both first-line SSRIs, but their side effect profiles differ significantly. While Lexapro tends to cause more weight gain, Zoloft has higher rates of gastrointestinal issues. Here's a detailed comparison to help you and your doctor choose the better option for your needs.
Head-to-Head Side Effect Comparison
| Side Effect | Zoloft | Lexapro | Key Difference |
|---|---|---|---|
| Nausea | 26% | 18% | Zoloft 45% more likely |
| Weight Gain (1yr) | +2.1 lbs avg | +4.6 lbs avg | Lexapro 2.2x greater |
| Sexual Dysfunction | 15-20% | 12-18% | Zoloft slightly worse |
| Insomnia | 16% | 12% | Zoloft more activating |
| Fatigue | 14% | 18% | Lexapro more sedating |
| Diarrhea | 20% | 8% | Zoloft 2.5x higher |
Key Finding:
A 2017 meta-analysis found Lexapro had 23% fewer discontinuations due to side effects compared to Zoloft, largely due to better GI tolerance.
Which Works Better for Specific Conditions?
1. Generalized Anxiety Disorder (GAD)
Lexapro may be preferred because:
- FDA-approved for GAD (Zoloft is off-label)
- More calming effect (less jitteriness)
- Works faster (2-3 weeks vs 3-4 for Zoloft)
2. Obsessive-Compulsive Disorder (OCD)
Zoloft is often better because:
- FDA-approved for OCD (Lexapro is off-label)
- Higher serotonin reuptake inhibition
- More effective for intrusive thoughts
3. Depression with Fatigue
Zoloft tends to be more activating, while Lexapro may worsen fatigue.
Metabolic Differences
Important variations in how your body processes these medications:
| Factor | Zoloft | Lexapro |
|---|---|---|
| Half-life | 26 hours | 27-32 hours |
| Liver Enzymes | CYP2C19, 3A4 | CYP2C19, 3A4 (less) |
| Food Effects | Take with food | No restriction |
⚠️ Dangerous Interaction:
Both medications increase bleeding risk when combined with NSAIDs or blood thinners. Lexapro has slightly lower interaction potential.
Switching Between Them
If changing from one to the other:
- Cross-taper over 2-4 weeks to avoid withdrawal
- Monitor for serotonin syndrome (rare but possible)
- Expect 2-week adjustment period for new side effects
Cost and Availability
- Zoloft: More generic options, typically $4-$10/month
- Lexapro: Fewer generics, usually $10-$25/month
- Both available in liquid forms for dose adjustment
FAQs About Zoloft vs Lexapro
1. Which has fewer sexual side effects?
Lexapro shows slightly lower rates (12-18% vs 15-20%), but individual responses vary greatly. Adding bupropion may help.
2. Is Zoloft more stimulating than Lexapro?
Yes. Zoloft's dopamine modulation makes it more activating - better for depressed patients with fatigue, worse for anxiety.
3. Which is better for long-term use?
Lexapro generally has better long-term tolerability, but Zoloft may be preferable for those needing ongoing activation.
Conclusion
While both Zoloft and Lexapro are effective SSRIs, key differences in GI effects, weight gain potential, and activation profiles make each better suited for different patients. Track your medication response with MedsideCheck to help your doctor personalize your treatment.
For more SSRI comparisons, see our article on Prozac side effects or learn about SSRI withdrawal symptoms.
If you're concerned about weight changes, read our guides to Metformin and weight and Lexapro weight gain.