Can You Take Zoloft and Wellbutrin Together?
Yes, you can take Zoloft (sertraline) and Wellbutrin (bupropion) together—this combination is commonly used in clinical practice and is generally well-tolerated when prescribed appropriately. 1, 2, 3
Evidence for Combination Therapy
Efficacy and Clinical Use
Combination therapy with bupropion and SSRIs (including sertraline) is effective for patients who have partial or inadequate responses to monotherapy. In clinical studies, approximately 70% of patients showed greater symptomatic improvement when bupropion was added to an SSRI compared to either medication alone. 2
The combination targets different neurotransmitter systems: sertraline primarily affects serotonin reuptake, while bupropion inhibits dopamine and norepinephrine reuptake, providing complementary mechanisms of action. 1, 3
This combination is particularly valuable for addressing SSRI-induced sexual dysfunction, which affects 41-63% of patients on sertraline alone but only 7-15% when bupropion is used. 4 Controlled studies support bupropion's effectiveness in reversing antidepressant-associated sexual dysfunction. 3
Safety Profile
The combination is generally well-tolerated with conservative dosing and close monitoring. 2 Adverse effects are similar to those seen with each medication individually, with no unique or serious side effects specifically attributable to the combination. 1
Common side effects during combination therapy include: sexual dysfunction (41%), insomnia (22%), fatigue (15%), and tremor (11%). 2 These rates are comparable to monotherapy profiles.
No seizures were reported in clinical series of patients taking both medications together, though bupropion does lower the seizure threshold and should be used cautiously in patients with seizure history. 5, 2
Important Prescribing Considerations
Typical dosing in combination therapy: bupropion 243 mg/day (average) combined with sertraline at standard therapeutic doses. 2 Start with lower doses and titrate gradually to minimize adverse effects.
Monitor for serotonin syndrome risk, though this is primarily a concern when combining multiple serotonergic agents or using MAOIs. 5 The combination of bupropion (non-serotonergic) with sertraline does not significantly increase this risk compared to sertraline alone.
Avoid this combination in patients with: uncontrolled hypertension, active seizure disorders, or those taking MAOIs (must wait 14 days after MAOI discontinuation). 5
Monitor blood pressure and heart rate, as both medications can cause modest increases. 5
Clinical Decision-Making
Prioritize this combination for patients who: have incomplete response to SSRI monotherapy, experience significant SSRI-induced sexual dysfunction, or have comorbid conditions that might benefit from bupropion (such as smoking cessation needs or concurrent ADHD). 5, 3
The combination may be particularly appropriate for patients with depression and comorbid obesity, as bupropion is a component of naltrexone-bupropion ER approved for weight management, while sertraline is weight-neutral compared to some other SSRIs. 5
Duration of treatment should follow standard depression guidelines: at least 4 months for a first episode, with consideration for prolonged treatment in recurrent depression. 5