Can Wellbutrin (bupropion) and sertraline be used together in a patient with depression?

Can Wellbutrin (Bupropion) and Sertraline Be Used Together?

Yes, bupropion and sertraline can be safely combined for treatment-resistant depression, with this combination showing efficacy in patients who have failed monotherapy with either agent alone. 1, 2, 3

Evidence Supporting Combination Therapy

The American College of Physicians found that augmenting an SSRI with bupropion decreased depression severity more than buspirone augmentation, with lower discontinuation rates due to adverse events. 2 This represents moderate-quality evidence for this combination strategy when initial monotherapy fails.

Clinical Efficacy

• Treatment-refractory patients who failed separate adequate trials of bupropion and sertraline individually showed clinical response when these medications were combined 3
• The combination may work through synergistic effects on distinct neurotransmitter systems: sertraline primarily affects serotonin reuptake while bupropion inhibits norepinephrine and dopamine reuptake 3
• No difference in response or remission rates was found compared to other augmentation strategies, but the combination showed a clear safety advantage 1, 2

Safety Profile and Monitoring

Serotonin Syndrome Risk

There is a theoretical but documented risk of serotonin syndrome when combining these medications, requiring vigilant monitoring especially during initiation and dose adjustments. 1, 4

• One case report documented serotonin syndrome in a patient on therapeutic doses of bupropion and sertraline, presenting with myoclonic jerks, confusion, and dysautonomia 4
• The mechanism may involve bupropion's inhibition of cytochrome P450 2D6, which increases SSRI blood levels 4
• Monitor for serotonin syndrome symptoms in the first 24-48 hours after starting combination therapy or any dose changes: mental status changes, neuromuscular hyperactivity (myoclonus, hyperreflexia), and autonomic instability (tachycardia, diaphoresis, hyperthermia) 1, 4

Common Pitfall to Avoid

Early manifestations of serotonin syndrome can be misinterpreted as worsening depression or anxiety, potentially leading to inappropriate medication escalation rather than discontinuation. 4 If a patient develops new confusion, agitation, or motor symptoms after combining these agents, consider serotonin syndrome first.

Practical Implementation

Starting the Combination

• When adding bupropion to existing sertraline therapy, start with low doses and titrate gradually 1
• If starting both simultaneously, begin each at lower doses than typical monotherapy targets
• Allow 2-4 weeks to assess full therapeutic effect before making further adjustments 1

Advantages of This Specific Combination

• Bupropion has significantly lower rates of sexual dysfunction (15% in men, 7% in women) compared to sertraline (63% in men, 41% in women), making this combination particularly useful when sexual side effects from SSRI monotherapy are problematic 5, 6
• The combination addresses multiple neurotransmitter systems simultaneously, potentially beneficial for patients with incomplete response to single-mechanism agents 3
• Bupropion does not cause the weight gain commonly associated with SSRIs 5

When to Consider This Combination

Use this combination after failure of adequate monotherapy trials with either agent alone, as recommended by guideline-based augmentation strategies. 1, 2

• Appropriate for patients with major depressive disorder who have not achieved remission with SSRI monotherapy 2, 3
• Consider earlier in patients experiencing sexual dysfunction on sertraline monotherapy, as bupropion may mitigate this side effect 5, 6
• Both agents showed similar efficacy (49-53% response rates) as monotherapy in bipolar depression when combined with mood stabilizers, though bupropion had lower switch rates to mania than other antidepressants 7, 8

Alternative Considerations

• Cognitive behavioral therapy combined with pharmacotherapy shows comparable outcomes to medication augmentation strategies and should be offered concurrently 1, 2
• Switching to a different SSRI or SNRI shows no difference in response rates compared to augmentation strategies, making this a reasonable alternative if combination therapy is not tolerated 2