Can Wellbutrin and Lexapro be combined? A Guide to Antidepressant Combination Therapy

October 9, 2025 •

3 min read

An estimated half of all people with major depressive disorder do not achieve full remission with the first antidepressant they try, making combination therapy a common strategy for enhanced relief. This has led many to question: Can Wellbutrin and Lexapro be combined? The answer is yes, but only under strict medical supervision and careful monitoring by a healthcare provider.

Quick Summary

Combining Wellbutrin and Lexapro is a medically-supervised strategy for depression and anxiety, especially for those with inadequate response to a single drug. This approach leverages different neurotransmitter pathways for broader symptom coverage and can offset some common side effects, like sexual dysfunction, but requires close monitoring for risks such as seizure and serotonin syndrome.

Key Points

Combination is Possible: Wellbutrin and Lexapro can be combined, but only under strict medical supervision and monitoring by a qualified healthcare provider.
Complementary Actions: Wellbutrin (NDRI) targets dopamine and norepinephrine, while Lexapro (SSRI) increases serotonin, allowing for broader symptom treatment.
Addresses SSRI Side Effects: Wellbutrin can help counteract common side effects of Lexapro, such as sexual dysfunction and fatigue, improving the tolerability of the regimen.
Manages Residual Symptoms: The combination is often used when a patient experiences only partial relief from a single medication, targeting symptoms like low energy and motivation.
Requires Close Monitoring: A doctor will carefully manage dosages and monitor for potential risks, including an increased seizure risk and the rare possibility of serotonin syndrome.
Tailored Approach: The decision to combine these medications is highly individualized, based on the patient's specific symptoms, medical history, and treatment response.

Understanding the Individual Medications

Before exploring the combined use, it is crucial to understand how Wellbutrin and Lexapro work independently. These two medications belong to different classes of antidepressants and target different neurotransmitter systems in the brain.

Lexapro (Escitalopram)

Lexapro is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels to help regulate mood, anxiety, and sleep. It is FDA-approved for major depressive disorder (MDD) and generalized anxiety disorder (GAD).

Wellbutrin (Bupropion)

Wellbutrin (bupropion) is a norepinephrine and dopamine reuptake inhibitor (NDRI) that affects norepinephrine and dopamine, which are linked to energy, motivation, focus, and pleasure. It's often used for depression with symptoms like low energy and lack of motivation, and is also FDA-approved for seasonal affective disorder (SAD) and smoking cessation.

The Rationale Behind Combining Wellbutrin and Lexapro

Combining these medications, known as augmentation, is a widely accepted strategy when a single antidepressant is only partially effective. This approach utilizes their complementary mechanisms to boost serotonin (Lexapro) and norepinephrine/dopamine (Wellbutrin), providing a more comprehensive treatment for diverse depression symptoms.

Enhanced Symptom Coverage

Combining can address lingering symptoms like low energy, fatigue, and poor concentration that SSRIs might not fully alleviate. This multi-mechanism approach recognizes the complex nature of depression.

Side Effect Management

A key benefit is mitigating SSRI side effects like sexual dysfunction, which is common with Lexapro. Wellbutrin has fewer sexual side effects and can counteract those caused by Lexapro. Wellbutrin can also help counter fatigue caused by Lexapro.

Potential Risks and How to Manage Them

Combining antidepressants requires careful medical supervision due to potential risks. Self-medicating is dangerous.

Increased Seizure Risk

Wellbutrin carries a seizure risk, especially at higher doses. While the interaction with Lexapro is generally low, doctors will manage dosages carefully, particularly for those with a history of seizures.

Serotonin Syndrome

Serotonin syndrome is a rare but serious condition from excess serotonin. Combining Wellbutrin, which can have indirect effects on serotonin, with Lexapro, an SSRI, requires caution. Symptoms include agitation, confusion, rapid heart rate, muscle rigidity, and high fever, requiring immediate medical attention.

Exacerbated Side Effects

Taking both medications can increase common side effects like anxiety, insomnia, dizziness, and sweating, especially initially. Doctors will monitor and adjust doses to minimize discomfort.

Comparison of Treatment Options


Feature	Wellbutrin Alone	Lexapro Alone	Wellbutrin + Lexapro Combination
Mechanism of Action	NDRI: affects norepinephrine and dopamine	SSRI: affects serotonin	Dual: affects serotonin, norepinephrine, and dopamine
Primary Benefits	Boosts energy, motivation, and focus; lower sexual side effects	Reduces anxiety, sadness, and promotes mood stability	Broader symptom coverage, improved energy, counters SSRI side effects
Common Side Effects	Insomnia, dry mouth, anxiety, headache, weight loss	Nausea, fatigue, headache, sexual dysfunction, weight changes	Potential for exacerbated side effects, like insomnia or anxiety
Best For	Depression with fatigue/low motivation, SAD, smoking cessation	Depression with co-occurring anxiety or generalized anxiety disorder	Treatment-resistant depression, depression with anxiety, managing SSRI side effects
Key Risks	Seizures (especially at high doses)	Sexual dysfunction, weight changes	Increased seizure risk, serotonin syndrome (rare), intensified side effects

Conclusion: Personalized Treatment Under Professional Care

Combining Wellbutrin and Lexapro offers a powerful approach for those who haven't found sufficient relief from a single antidepressant. By targeting different neurotransmitters, it can address a wider range of symptoms, including boosting energy and countering SSRI sexual side effects. However, this strategy requires medical expertise for safety, as Wellbutrin can increase Lexapro blood levels. Close monitoring is vital to manage potential risks like seizure and serotonin syndrome. Always consult your doctor before combining or adjusting antidepressant therapy to determine the safest and most appropriate treatment for your specific needs and history.

Authoritative Source

This information is for educational purposes only and is not a substitute for professional medical advice. For more detailed information on antidepressant research, visit the National Institutes of Health (NIH) website.

Additional Considerations

Long-Term Adherence: Managing side effects effectively can improve long-term adherence.
Individualized Response: Response to combination therapy varies based on individual neurochemistry.
Therapy is Key: Medications are often most effective when combined with psychotherapy.
Alcohol Precautions: Limiting alcohol is crucial, especially with this combination, due to increased seizure risk.

Finding the right mental health treatment involves collaboration with a healthcare provider, and the Wellbutrin-Lexapro combination can be a valuable tool when used correctly.

Visit the NIH website for research on mental health

Frequently Asked Questions

A doctor might prescribe both Wellbutrin and Lexapro to treat depression and/or anxiety when a patient has not achieved a full response to either medication alone. The combination targets different brain chemicals to provide more comprehensive relief and can help counteract side effects like sexual dysfunction caused by Lexapro.

Potential risks of combining Wellbutrin and Lexapro include an increased risk of seizures, a rare but serious condition called serotonin syndrome, and intensified side effects like insomnia or anxiety. This is why the combination requires close medical supervision.

Yes, Wellbutrin can help mitigate the sexual side effects, such as reduced libido, that are commonly associated with SSRIs like Lexapro. This is a frequent reason for using the combination therapy.

Wellbutrin is an NDRI that primarily affects norepinephrine and dopamine, boosting energy and motivation. Lexapro is an SSRI that increases serotonin levels, which is more effective for regulating mood and anxiety.

Serotonin syndrome is a potentially life-threatening condition caused by an excess of serotonin. While Wellbutrin doesn't directly increase serotonin, it can indirectly affect levels. Combining it with Lexapro, an SSRI, requires close monitoring to avoid this risk.

Wellbutrin, particularly at higher doses, can increase the risk of seizures. Combining it with Lexapro requires a doctor to carefully manage dosages and monitor patients, especially those with pre-existing risk factors.

For some patients, yes. Increasing the Lexapro dose can lead to more side effects without additional benefits, especially if the remaining symptoms are related to energy or motivation. The combination provides a different pharmacological approach by targeting multiple neurotransmitter systems.

You should schedule a consultation with your healthcare provider or a psychiatric specialist to discuss your symptoms and treatment options. They can assess your needs and determine if combining Wellbutrin and Lexapro is the safest and most effective path for you.