Lexapro (escitalopram) and Wellbutrin (bupropion) are among the top 3 most prescribed antidepressants in the United States — but they couldn't be more different. Lexapro is an SSRI that boosts serotonin; Wellbutrin is an NDRI that boosts norepinephrine and dopamine. For many patients, the switch from one to the other is life-changing.
Why People Switch from Lexapro to Wellbutrin
The most common reasons:
- Sexual dysfunction: 40–70% of SSRI users experience decreased libido, delayed orgasm, or erectile dysfunction. Wellbutrin has virtually zero sexual side effects — in fact, it's sometimes prescribed specifically to counteract SSRI-related sexual problems (see our SSRI sexual side effects guide)
- Weight gain: SSRIs can cause 5–15 lbs of weight gain over 6–12 months. Wellbutrin is weight-neutral or even promotes modest weight loss
- Emotional blunting: Many SSRI users report feeling "flat," "numb," or unable to cry or feel joy. Wellbutrin's dopaminergic action tends to restore emotional range
- Fatigue and low energy: Wellbutrin is mildly stimulating, which helps patients who feel sedated on SSRIs
- Smoking cessation: Wellbutrin (marketed as Zyban) is also FDA-approved for smoking cessation
Key Differences: Lexapro vs. Wellbutrin
| Feature | Lexapro (SSRI) | Wellbutrin (NDRI) |
|---|---|---|
| Mechanism | Increases serotonin | Increases norepinephrine + dopamine |
| Sexual side effects | Very common (40–70%) | Rare (<2%) |
| Weight effect | Gain or neutral | Neutral or modest loss |
| Energy level | Neutral or sedating | Mildly activating |
| Anxiety treatment | Excellent (GAD, panic, social) | Can worsen anxiety initially |
| Seizure risk | Very low | Dose-dependent (avoid >450 mg/day) |
| Available as generic | Yes | Yes |
| Cost (generic) | $5–20/month | $10–30/month |
Important: When Wellbutrin Is NOT the Right Switch
Wellbutrin is not a good choice if you have:
- Anxiety-predominant depression — Wellbutrin can increase anxiety, especially in the first 2 weeks
- Panic disorder — Wellbutrin may worsen panic attacks
- History of seizures or eating disorders — Wellbutrin lowers the seizure threshold
- Bipolar disorder — Higher risk of triggering mania
If anxiety is your primary symptom, discuss alternatives like switching to a different SSRI, an SNRI, or adding Caplyta as augmentation.
The Cross-Taper Protocol
The safest approach is a cross-taper — gradually reducing Lexapro while slowly introducing Wellbutrin:
Example: Switching from Lexapro 10 mg
- Week 1–2: Continue Lexapro 10 mg. Start Wellbutrin XL 150 mg in the morning
- Week 3–4: Reduce Lexapro to 5 mg. Continue Wellbutrin XL 150 mg
- Week 5–6: Reduce Lexapro to 2.5 mg (half a 5 mg tablet or liquid). Continue Wellbutrin 150 mg
- Week 7: Stop Lexapro. If Wellbutrin is tolerated, doctor may increase to 300 mg
Example: Switching from Lexapro 20 mg
- Week 1–2: Reduce Lexapro to 15 mg. Start Wellbutrin XL 150 mg
- Week 3–4: Reduce Lexapro to 10 mg
- Week 5–6: Reduce Lexapro to 5 mg
- Week 7–8: Reduce Lexapro to 2.5 mg
- Week 9: Stop Lexapro. Consider increasing Wellbutrin to 300 mg
What to Expect During the Switch
First 1–2 weeks: You may feel increased energy (from Wellbutrin) alongside some Lexapro withdrawal symptoms (mild dizziness, irritability). This is normal.
Weeks 2–4: Anxiety may briefly increase. Sexual function and energy usually begin improving.
Weeks 4–8: Wellbutrin reaches full therapeutic effect. Mood stabilizes. SSRI side effects resolve.
By week 12: Most patients are fully adjusted and can assess whether the switch was beneficial.
What About Taking Both Together?
Some patients use Lexapro + Wellbutrin as a combination therapy rather than a complete switch. This is called augmentation and can be effective because:
- Wellbutrin counteracts SSRI sexual side effects
- The two target different neurotransmitter systems (serotonin + dopamine/norepinephrine)
- The combination can provide broader symptom relief than either alone
This approach requires careful monitoring for drug interactions and side effects.
The Bottom Line
Switching from Lexapro to Wellbutrin is one of the most common and successful antidepressant transitions — especially for patients struggling with sexual dysfunction, weight gain, or emotional flatness. The key is a slow cross-taper, realistic expectations about the adjustment period, and honest communication with your prescriber.
For the complete picture on antidepressant transitions, read our Complete Guide to Switching Antidepressants.
This article is for informational purposes only. Never stop or change your medication without consulting your prescriber. If you are in crisis, contact the 988 Suicide & Crisis Lifeline by calling or texting 988.