Switching from Bupropion to Sertraline
A direct switch from bupropion to sertraline can be performed safely without a washout period or cross-taper, as these medications have different mechanisms of action and no significant pharmacokinetic interactions. 1
Switching Protocol
Direct Switch Strategy
- Stop bupropion and start sertraline the next day at the standard initial dose of 25-50 mg daily 1
- No tapering of bupropion is required before switching, as it does not cause significant withdrawal symptoms when discontinued 2
- No washout period is necessary between medications, as bupropion (a norepinephrine-dopamine reuptake inhibitor) and sertraline (an SSRI) do not have problematic drug interactions 1
Sertraline Dosing After Switch
- Start sertraline at 25-50 mg per day (morning or evening) 1
- Maximum dose is 200 mg per day 1
- Sertraline is well tolerated and has less effect on metabolism of other medications compared to other SSRIs 1
Evidence Supporting Direct Switch
The STAR*D trial and subsequent American College of Physicians guidelines demonstrate that switching between second-generation antidepressants (including bupropion and sertraline) shows no difference in efficacy or safety outcomes 1. Moderate-quality evidence confirms no difference in response, remission, or adverse event discontinuation when switching from bupropion to sertraline versus other switch strategies 1.
Important Clinical Considerations
Timeline for Response
- Allow 4-8 weeks for full therapeutic trial of sertraline after switching 1
- Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects appear 1
Common Side Effects to Monitor
- Sertraline-specific adverse effects include sweating, tremors, nervousness, insomnia or somnolence, dizziness, gastrointestinal disturbances, and sexual dysfunction 1
- Sexual dysfunction occurs significantly more frequently with sertraline (41-63% of patients) compared to bupropion (7-15% of patients) 3, 4, 5
- Nausea, diarrhea, and somnolence are more common with sertraline than bupropion 5
Key Pitfalls to Avoid
- Do not use conservative tapering strategies (gradual taper followed by washout period) when switching from bupropion to sertraline, as this unnecessarily prolongs periods without adequate treatment and risks depressive exacerbation 2
- Monitor for treatment-emergent activation or agitation in the first 1-2 weeks, as bupropion is activating while sertraline is less so 1
- Counsel patients about potential sexual side effects before switching, as this is a major reason for treatment discontinuation with sertraline 3, 4