How to Switch from Lexapro 20 mg to Wellbutrin XR 150 mg
You should perform a direct switch by starting Wellbutrin XR 150 mg daily while simultaneously tapering escitalopram over 1-2 weeks, as these medications have different mechanisms of action (escitalopram is an SSRI metabolized by CYP2C19, while bupropion is a norepinephrine-dopamine reuptake inhibitor metabolized by CYP2B6) and do not have significant pharmacokinetic interactions that would require a washout period. 1, 2
Recommended Switching Strategy
Week 1:
- Start Wellbutrin XR 150 mg once daily in the morning (take on empty stomach or with food - doesn't matter) 1
- Simultaneously reduce Lexapro to 10 mg daily
- Swallow Wellbutrin XR whole - do not crush, divide, or chew (increases seizure risk) 1
Week 2:
- Continue Wellbutrin XR 150 mg daily
- Reduce Lexapro to 5 mg daily
Week 3 onward:
- Continue Wellbutrin XR 150 mg daily
- Discontinue Lexapro completely
Critical Monitoring Points
Monitor closely within the first 1-2 weeks for:
- Increased anxiety or agitation (bupropion can be activating, especially at initiation) 3
- Insomnia (minimize by avoiding bedtime doses - take in morning) 1
- Suicidal ideation (FDA black box warning for all antidepressants) 4
- SSRI discontinuation symptoms from tapering escitalopram (dizziness, paresthesias, flu-like symptoms) 2
Important Caveats
Seizure Risk Management:
Bupropion carries seizure risk, particularly at higher doses. The 150 mg starting dose is appropriate and safe. Do not exceed 450 mg/day maximum. If increasing dose is needed, wait at least 4 weeks at 150 mg before considering escalation to 300 mg. 1
Anxiety Considerations:
If the patient has significant comorbid anxiety, use caution. Bupropion can worsen anxiety symptoms, particularly during initiation, though clinical trials show comparable efficacy to SSRIs for mild-to-moderate anxiety in depressed patients. 3 The cross-taper approach allows you to maintain some SSRI coverage during the transition period, which may buffer against anxiety exacerbation.
Sexual Function:
One advantage of this switch: bupropion has significantly lower rates of sexual dysfunction compared to escitalopram and other SSRIs. 4 This is often a primary reason for switching.
When to Assess Response:
Full antidepressant effect may not be evident until 4 weeks of treatment or longer at the target dose. 1 If no clinical improvement after 6-8 weeks, consider dose adjustment or alternative strategies. 4
Alternative Conservative Approach:
If the patient has severe anxiety, history of seizures, or you're concerned about overlapping medications, you could taper escitalopram completely over 2-3 weeks first, then start bupropion after a brief 3-5 day washout. However, this leaves the patient without antidepressant coverage and risks depressive relapse. 2
The cross-taper method is preferred in real-world practice because it maintains therapeutic coverage throughout the transition and these two medications don't have problematic pharmacokinetic interactions. 2, 5