From the Guidelines
Prescribing Wellbutrin (bupropion) and Zoloft (sertraline) together can be safe and is a relatively common practice in psychiatry, as long as patients are closely monitored for potential side effects and interactions, as recommended by the American College of Physicians 1.
Key Considerations
- The combination of Wellbutrin and Zoloft is often used when a single antidepressant doesn't adequately relieve symptoms, and they have complementary mechanisms of action, with Wellbutrin working primarily on norepinephrine and dopamine neurotransmitters, and Zoloft affecting serotonin.
- Patients should be monitored for potential side effects including increased anxiety, insomnia, dry mouth, headaches, or rarely, increased risk of seizures, as well as sexual adverse events, which are less common with bupropion compared to fluoxetine or sertraline 1.
- The American College of Physicians recommends that clinicians assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy, and modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.
Important Recommendations
- The American College of Physicians recommends that clinicians select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences, and that they discuss adverse event profiles with patients before selecting a medication 1.
- Clinicians should consider the potential risks and benefits of the combination, including the increased risk of nonfatal suicide attempts associated with SSRIs, and the potential for bupropion to counteract some Zoloft-induced sexual side effects or fatigue.
- Patients with certain medical conditions, such as seizure disorders, eating disorders, or those taking other medications that might interact, should be carefully evaluated before starting this combination.
From the Research
Safety of Prescribing Wellbutrin and Zoloft Together
- The combination of bupropion (Wellbutrin) and selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft) has been associated with a risk of serotonin syndrome, a potentially fatal complication 2, 3.
- Serotonin syndrome is characterized by symptoms such as myoclonic jerks, clumsiness, gait difficulties, confusion, forgetfulness, agitation, and lethargy 2.
- A case report described a 62-year-old woman who developed serotonin syndrome after taking bupropion and sertraline together, highlighting the potential for misinterpretation of early symptoms as signs of worsening depression 2.
- Another case report described a 15-year-old boy who developed serotonin syndrome after taking bupropion alone, with serum bupropion and hydroxybupropion levels above therapeutic ranges 3.
Efficacy of Combination Treatment
- Some studies suggest that the combination of bupropion and SSRIs like sertraline may be effective for treating refractory depression, with synergistic effects on serotonergic, dopaminergic, and noradrenergic systems 4, 5.
- A review of the literature found that controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, and that combination treatment with bupropion and an SSRI or SNRI may be effective for treating MDD in patients refractory to single-agent treatment 5.
Precautions and Considerations
- The available data suggest that the combination of bupropion and either an SSRI or an SNRI is generally well tolerated, but additional randomized controlled studies are needed to answer important questions regarding optimal dose and duration of treatment 5.
- A retrospective study found that the concurrent administration of selegiline and selective serotonin reuptake inhibitors should be avoided due to literature-reported interactions, but bupropion may be a reasonable choice in combination with selegiline 6.