Transitioning from Sertraline to Bupropion: Timing and Protocol
When switching from sertraline 100 mg to bupropion, you should gradually taper sertraline while starting bupropion after sertraline is reduced to 50 mg or lower to minimize risk of serotonin syndrome and withdrawal effects. 1, 2
Tapering Sertraline Protocol
- Begin by reducing sertraline from 100 mg to 50 mg daily for 1-2 weeks while monitoring for withdrawal symptoms 1
- SSRIs including sertraline should always be slowly tapered when discontinued to minimize risk of withdrawal effects 1
- Abrupt discontinuation or major dose reduction is unacceptable medical care and can lead to significant adverse effects 1
- The standard effective dose of sertraline is 50 mg daily, making this a reasonable intermediate step in the taper 3
Initiating Bupropion
- Start bupropion only after sertraline has been reduced to 50 mg or lower to minimize risk of drug interactions 2
- For Bupropion SR (sustained release), begin with 150 mg once daily for 3 days, then increase to the standard maintenance dose of 150 mg twice daily if tolerated 4
- For Bupropion XL (extended release), start with 150 mg once daily, with a maintenance dose of 150-300 mg once daily 4
- Monitor closely during the first 1-2 weeks after initiating bupropion for adverse effects, including agitation, irritability, or unusual changes in behavior 1
Completing the Transition
- After 1-2 weeks of combined therapy at lower doses, further reduce sertraline to 25 mg daily for 1 week before complete discontinuation 1
- Continue bupropion at the established effective dose (typically 300 mg daily for SR formulation or 150-300 mg for XL formulation) 4, 5
- Assess therapeutic response to bupropion after 4-6 weeks of treatment at the target dose 5
Special Considerations and Cautions
- There is a risk of serotonin syndrome when combining bupropion with sertraline, particularly at higher doses of both medications 2
- Early symptoms of serotonin syndrome can include myoclonic jerks, confusion, and alternating agitation and lethargy, which might be misinterpreted as worsening depression 2
- Bupropion may be particularly beneficial for patients concerned about sexual dysfunction, as it has significantly lower rates of sexual side effects compared to sertraline (15% vs 63% in men; 7% vs 41% in women) 6, 7
- Bupropion is contraindicated in patients with seizure disorders as it lowers the seizure threshold 4, 5
- Avoid combining with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs 4
Monitoring During Transition
- Monitor patients closely during the first 1-2 weeks of the transition for both withdrawal symptoms from sertraline and adverse effects from bupropion 1
- Assess for emergence of agitation, irritability, unusual changes in behavior, or suicidal thoughts, as these can indicate worsening depression or adverse medication effects 1
- If intolerable withdrawal symptoms occur during sertraline taper, slow the taper rate further 1
- If adverse effects from bupropion occur, consider maintaining a lower dose (150 mg daily) until sertraline is completely discontinued 4
This protocol prioritizes patient safety by minimizing the risk of drug interactions while ensuring effective treatment of depression throughout the transition period.