Can a Patient Start Wellbutrin After Stopping Zoloft for a Few Days?
Yes, a patient can start Wellbutrin (bupropion) a few days after stopping Zoloft (sertraline), as there is no required washout period between these medications and they can even be safely combined. 1
Key Safety Considerations
No Washout Period Required
- Sertraline and bupropion do not require a washout period when switching between them, unlike transitions involving MAOIs which require 14 days 1
- Sertraline has a relatively short half-life compared to other SSRIs (like fluoxetine), making transitions more straightforward 1
- These medications can actually be used in combination safely, as demonstrated in the STAR*D trial where bupropion was used to augment SSRIs including sertraline 1, 2
Discontinuation Syndrome Risk
- Monitor for SSRI discontinuation syndrome from stopping sertraline, which can include dizziness, fatigue, myalgias, headaches, nausea, insomnia, anxiety, and irritability 1
- Sertraline is specifically noted as one of the SSRIs associated with discontinuation syndrome (along with paroxetine and fluvoxamine) 1
- Discontinuing antidepressants over 10-14 days limits withdrawal symptoms, so abrupt cessation after only a few days may cause these symptoms 1
Serotonin Syndrome Considerations
- Bupropion has minimal serotonergic activity, making serotonin syndrome extremely unlikely in this transition 3, 4
- While one case report exists of serotonin syndrome with bupropion plus SSRIs, this was attributed to bupropion's inhibition of CYP2D6 increasing SSRI levels when used concurrently—not relevant when sertraline has been stopped 5
- The primary concern for serotonin syndrome involves combining multiple serotonergic agents, particularly MAOIs, which does not apply here 1
Practical Implementation
Starting Bupropion
- Begin with 150 mg once daily for 3 days, then increase to 150 mg twice daily if tolerated 1
- Maximum dose is 300 mg per day (450 mg for immediate-release formulation) 1, 3
- Give the second dose before 3 PM to minimize insomnia risk 1
Monitoring Requirements
- Watch for bupropion-specific adverse effects: agitation, insomnia, dry mouth, headaches, nausea 1, 3
- Screen for seizure risk factors (history of seizures, eating disorders, brain metastases, stroke) as bupropion is contraindicated in these patients 1
- Monitor for neuropsychiatric symptoms (depression worsening, suicidal ideation), though recent large trials show no increased risk compared to other antidepressants 1
- Expect therapeutic response within 2 weeks with full efficacy at 4 weeks 3, 4
Clinical Advantages of This Switch
- Bupropion has significantly lower rates of sexual dysfunction (15% in men, 7% in women) compared to sertraline (63% in men, 41% in women) 6
- Bupropion is activating rather than sedating, which may benefit patients with low energy 1, 3
- No anticholinergic effects or cardiac conduction problems compared to tricyclics 4
- Evidence from STAR*D shows similar remission rates (21-25%) when switching to bupropion after SSRI failure 2
Critical Contraindications
Do not use bupropion in patients with: