Initiating Bupropion in a Patient on Sertraline 100 mg Daily
You can start bupropion immediately without tapering or discontinuing sertraline, beginning with 37.5 mg every morning and titrating by 37.5 mg every 3 days as tolerated, with a target dose of 150 mg twice daily (maximum 300 mg/day). 1
Immediate Initiation Strategy
There is no required washout period or dose adjustment of sertraline when adding bupropion. 1 The combination of bupropion and sertraline addresses depression through complementary mechanisms—sertraline affects serotonin while bupropion works via noradrenergic/dopaminergic pathways. 1
Starting Dose and Titration Schedule
Start with 37.5 mg once daily in the morning to minimize adverse effects and assess tolerability in patients on multiple medications. 1
Increase by 37.5 mg every 3 days as tolerated until reaching therapeutic effect or the maximum recommended dose. 1
Target dose is 150 mg twice daily (300 mg total daily dose), which is the standard therapeutic dose for major depressive disorder. 1
Administer the second dose before 3 PM to minimize the risk of insomnia, particularly important given bupropion's activating properties. 1
Critical Timing Considerations
The first dose should be given in the morning to leverage bupropion's activating properties, which can improve energy levels and reduce apathy. 1
The gradual titration schedule is necessary to minimize seizure risk while achieving therapeutic levels. 1
This low-and-slow approach is especially important in patients already on psychotropic medications to assess tolerability. 1
Pre-Treatment Screening Requirements
Before initiating bupropion, you must screen for absolute contraindications:
Seizure disorders or conditions that lower seizure threshold (eating disorders, abrupt discontinuation of alcohol/benzodiazepines/antiepileptic drugs). 1
Current MAOI use or within 14 days of discontinuing MAOIs. 1
Uncontrolled hypertension, as bupropion can elevate blood pressure and heart rate. 1
Severe hepatic impairment (maximum dose 150 mg daily if present). 1
Moderate to severe renal impairment (reduce total daily dose by half if GFR <90 mL/min). 1
Monitoring Parameters
Monitor for increased agitation in the first 1-2 weeks, as bupropion is an activating medication. 1
Watch for suicidal ideation, particularly in patients under 24 years old who require close monitoring for increased suicidal thoughts during the first 1-2 months of treatment. 1
Check blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations in both. 1
Assess therapeutic response at 6-8 weeks at an adequate dose before considering treatment modification. 1
Clinical Rationale for Combination Therapy
This combination may be particularly beneficial for patients with:
Comorbid depression and low energy or apathy, as bupropion can improve energy levels. 1
SSRI-induced sexual dysfunction, as bupropion has lower rates of sexual dysfunction compared to SSRIs and can actually improve sexual functioning when added to SSRI treatment. 2
Inadequate response to sertraline monotherapy, as augmenting SSRIs with bupropion decreases depression severity more than augmentation with buspirone. 1
Common Pitfalls to Avoid
Do not delay initiation waiting for sertraline adjustment—there is no pharmacokinetic interaction requiring dose modification of either medication. 1
Do not start at higher doses (such as 150 mg daily) in patients on multiple psychotropic medications, as this increases risk of adverse effects and seizures. 1
Do not administer the second dose late in the day, as this significantly increases insomnia risk. 1
Do not exceed 300 mg total daily dose for depression treatment to maintain seizure risk at approximately 0.1%. 1, 3