What is the recommended approach when using Zoloft (sertraline) and Wellbutrin (bupropion) in combination therapy?

Combination Therapy with Zoloft (Sertraline) and Wellbutrin (Bupropion)

The combination of sertraline (Zoloft) and bupropion (Wellbutrin) is an effective approach for treating major depressive disorder (MDD) when monotherapy is inadequate, particularly for patients experiencing sexual dysfunction or incomplete symptom remission with sertraline alone. 1

Indications for Combination Therapy

• Primary indications:

  • Incomplete symptom remission with sertraline monotherapy
  • Sexual side effects from sertraline (bupropion can help reverse these)
  • Treatment-resistant depression not responding to either medication alone

• Potential benefits:

  • Improved antidepressant response through complementary mechanisms
  • Reduction of SSRI-associated sexual dysfunction
  • Counterbalancing of side effects (bupropion's activating properties may offset sertraline's potential sedating effects)

Patient Selection Considerations

• Ideal candidates:

  • Patients with depression who have had partial response to sertraline
  • Patients experiencing sexual dysfunction on sertraline
  • Patients with low energy or fatigue as prominent symptoms

• Use caution in:

  • Patients with significant anxiety (bupropion may exacerbate anxiety symptoms) 2
  • Patients with seizure disorders (bupropion lowers seizure threshold) 2
  • Patients with uncontrolled hypertension 2

Dosing Strategy

1. Initial approach:

   • Start with sertraline monotherapy (typically 50-200 mg daily)
   • Add bupropion after establishing sertraline tolerability
   • Begin bupropion at lower doses (e.g., 150 mg daily) 2
   • Administer bupropion doses earlier in the day to minimize insomnia risk 2

2. Titration:

   • Gradually increase bupropion by 75-100 mg increments
   • Maximum bupropion dose typically 300-400 mg/day (divided doses)
   • Maximum sertraline dose typically 200 mg/day

3. Timing considerations:

   • Give second bupropion dose before 3 p.m. to minimize insomnia 2
   • Sertraline can be taken morning or evening based on patient tolerance

Monitoring and Management

• Regular monitoring:

  • Blood pressure and heart rate (especially during first 12 weeks) 2
  • Emergence or worsening of anxiety symptoms
  • Sexual function improvement
  • Sleep quality
  • Suicidal thoughts (particularly in patients under 24 years) 2

• Managing side effects:

  • For emergent anxiety: consider reducing bupropion dose or administering earlier in day 2
  • For insomnia: ensure bupropion doses are taken earlier in day
  • For persistent side effects: adjust doses of either medication before discontinuing

Efficacy Evidence

Research supports the effectiveness of this combination:

• Open-label studies show response rates of approximately 60% and remission rates of 50% with SSRI-bupropion combinations 3
• The combination has demonstrated effectiveness for treatment-resistant depression 1, 4, 5
• Bupropion specifically helps reverse SSRI-associated sexual dysfunction 1, 6

Potential Adverse Effects

• Common side effects:

  • Insomnia, dry mouth, headache, anxiety/jitteriness 2
  • Decreased appetite, nausea 2
  • Increased blood pressure and heart rate 2

• Serious but rare concerns:

  • Seizures (risk increases with higher bupropion doses) 2
  • Serotonin syndrome (though risk is lower than with MAOI combinations) 7
  • Neuropsychiatric symptoms 2

Special Considerations

• Dose adjustments needed for:

  • Moderate to severe renal impairment (reduce bupropion by 50%) 2
  • Moderate to severe hepatic impairment (lower doses of both medications) 2
  • Elderly patients (consider lower starting doses) 7, 2

• Discontinuation:

  • Gradual tapering recommended when discontinuing either medication
  • More cautious tapering for patients on long-term treatment or higher doses 2

Clinical Pearls

• Bupropion's norepinephrine and dopamine effects complement sertraline's serotonergic effects
• This combination may be particularly helpful for patients with fatigue, low motivation, or sexual dysfunction
• Avoid this combination in patients with seizure disorders or uncontrolled anxiety
• Morning dosing of bupropion and evening dosing of sertraline may optimize tolerability