Can we switch a patient from Sertraline (Selective Serotonin Reuptake Inhibitor) to Wellbutrin (Bupropion)?

Switching from Sertraline to Wellbutrin (Bupropion)

Yes, you can switch directly from sertraline to bupropion without a washout period or cross-taper, as these medications have different mechanisms of action and no significant pharmacokinetic interactions. 1

Direct Switch Protocol

Stop sertraline and start bupropion the next day at the standard initial dose. 1 This direct switching approach is safe because:

• Bupropion (a norepinephrine-dopamine reuptake inhibitor) and sertraline (an SSRI) do not have problematic drug interactions 1
• No washout period is necessary between these medications 1
• Switching between second-generation antidepressants shows no difference in efficacy or safety outcomes (moderate-quality evidence) 1

Bupropion Dosing After Switch

Start bupropion extended-release at 150 mg once daily in the morning. 2

• After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily 2
• Bupropion should be swallowed whole and not crushed, divided, or chewed 2
• May be taken with or without food 2
• Increase the dose gradually to minimize seizure risk 2

Sertraline Discontinuation Considerations

Taper sertraline over 10-14 days to limit withdrawal symptoms if the patient has been on it for an extended period. 1 However, the direct switch protocol from the American Academy of Family Physicians suggests stopping sertraline and starting bupropion the next day is acceptable 1, so clinical judgment is needed based on:

• Duration of sertraline treatment
• Current sertraline dose
• Patient's history of discontinuation symptoms

Timeline for Response

Allow 4-8 weeks for a full therapeutic trial of bupropion after switching. 1

• Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects appear 1
• After 9 months of successful treatment, consider dosage reduction to reassess the need for continued medication 1

Monitoring and Key Differences

Monitor for treatment-emergent activation or agitation in the first 1-2 weeks. 1 This is important because:

• Bupropion is activating while sertraline is less so 1
• Patients may experience increased energy or restlessness initially

Watch for changes in side effect profile:

• Sertraline-associated effects that may resolve: sweating, tremors, sexual dysfunction, gastrointestinal disturbances 1
• Bupropion-specific effects to monitor: insomnia, dry mouth, headache, nausea, constipation, and seizure risk (especially at doses >300 mg/day or in patients with predisposing factors) 2

Special Populations and Contraindications

Bupropion is contraindicated in patients with:

• Seizure disorders or conditions that increase seizure risk 2
• Current or prior diagnosis of bulimia or anorexia nervosa 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Use of MAOIs within 14 days 2

Dose adjustments required for:

• Moderate to severe hepatic impairment: maximum dose 150 mg every other day 2
• Mild hepatic impairment: consider reducing dose and/or frequency 2
• Renal impairment (GFR <90 mL/min): consider reducing dose and/or frequency 2

Evidence for Switch Efficacy

Following nonefficacy with an initial SSRI, approximately 21% of patients remit with a second-step switch to another antidepressant (including bupropion). 3 Key findings:

• About 80% of patients complete at least 6 weeks of treatment with the switch medication 3
• Half of responses and two-thirds of remissions occur after 6 weeks of treatment 3
• A 12-week trial duration captures the maximum number of responders 3
• Patients with at least 20% reduction in depressive symptoms around week 2 are 6 times more likely to respond or remit 3

Clinical Advantages of This Switch

Bupropion has significantly fewer sexual side effects compared to sertraline. 4 In a direct comparison:

• 63% of men and 41% of women on sertraline developed sexual dysfunction 4
• Only 15% of men and 7% of women on bupropion developed sexual dysfunction 4
• Sexual dysfunction with sertraline appeared as early as day 7 and persisted throughout treatment 4

This makes bupropion particularly appropriate when sexual dysfunction is a concern or was a reason for switching from sertraline 4.

Common Pitfalls to Avoid

Do not combine bupropion with MAOIs or use within 14 days of MAOI discontinuation. 2 At least 14 days should elapse between stopping bupropion and starting an MAOI 2.

Do not exceed 300 mg/day of bupropion extended-release without careful consideration of seizure risk. 2 The dose-dependent seizure risk increases significantly above this threshold.

Do not assume lack of early response means treatment failure. 3 One-third of responses occur after 9 weeks of treatment, so premature discontinuation may miss potential responders 3.