Do Wellbutrin and Lexapro work well together?

October 10, 2025 •

3 min read

According to research, combining Wellbutrin and Lexapro can be a safe and effective strategy for treating depression in some patients, though it requires close medical supervision. This article explores the details of how and why do Wellbutrin and Lexapro work well together in a combination therapy approach.

Quick Summary

Combining Wellbutrin and Lexapro is a common strategy for treatment-resistant depression, leveraging different mechanisms to improve symptoms. It can offer more comprehensive relief but also carries specific risks, like serotonin syndrome, requiring careful monitoring.

Key Points

Complementary Action: Wellbutrin targets dopamine and norepinephrine, while Lexapro targets serotonin, allowing for broader symptom coverage.
Augmentation Strategy: The combination is often used when a patient doesn't achieve full remission on Lexapro alone, or to address specific residual symptoms.
Mitigating Side Effects: Wellbutrin can help counteract some common sexual side effects and fatigue associated with Lexapro.
Risk of Serotonin Syndrome: There is a rare but serious risk of serotonin syndrome when combining these, especially at higher doses or with other serotonergic drugs, requiring close medical supervision.
Individualized Treatment: The decision to combine these medications is highly personalized and should only be made with a healthcare provider who considers your specific symptoms and medical history.
Enhanced Efficacy: Studies suggest that the combination can lead to higher response and remission rates for patients with MDD than either drug alone.

Understanding the Rationale Behind Combination Therapy

For many patients, finding the right treatment for major depressive disorder (MDD) can be a process. If a single antidepressant isn't fully effective, a healthcare provider might suggest adding a second medication. This strategy, known as augmentation therapy, often involves combining an atypical antidepressant like Wellbutrin (bupropion) with a selective serotonin reuptake inhibitor (SSRI) like Lexapro (escitalopram). The effectiveness of this combination stems from their different ways of working, targeting various chemical messengers in the brain to address a broader range of depressive symptoms.

How Each Medication Works

Lexapro primarily affects serotonin, a neurotransmitter that influences mood, sleep, and appetite, by preventing its reuptake. Increasing serotonin can help reduce anxiety and improve mood. Wellbutrin, on the other hand, impacts dopamine and norepinephrine, neurotransmitters vital for motivation, focus, and energy, by blocking their reuptake. Used together, they offer a more comprehensive approach to managing depression.

Reasons for Combining Wellbutrin and Lexapro

The combination is often used to address the varied symptoms of depression, as Lexapro is effective for mood and anxiety while Wellbutrin helps with low energy, motivation, and concentration. Another key reason is to counter common sexual side effects associated with SSRIs like Lexapro, as Wellbutrin has a lower incidence of these issues and can improve quality of life and treatment adherence. For patients who only partially improve with a single medication, adding the second drug can enhance the antidepressant effect, potentially leading to higher remission rates.

Potential Risks and Considerations

While beneficial, combining these medications requires careful medical management due to potential risks.

Common Side Effects and Monitoring

Patients may experience amplified side effects, especially early in treatment. These can include insomnia, anxiety, dry mouth, sweating, headaches, and nausea. Close monitoring by a healthcare professional is crucial to manage these effects.

Serious Risks

Though rare, serious risks include Serotonin Syndrome, a life-threatening condition from excessive serotonin that can occur when combining an SSRI like Lexapro with other drugs that affect serotonin, even indirectly like Wellbutrin. Symptoms such as rapid heart rate and confusion require immediate medical care. Wellbutrin also increases seizure risk in a dose-dependent manner, and combining it with another antidepressant can further lower the seizure threshold, especially for those with a history of seizures or certain medical conditions.

Comparison of Wellbutrin and Lexapro


Feature	Wellbutrin (Bupropion)	Lexapro (Escitalopram)
Drug Class	Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)	Selective Serotonin Reuptake Inhibitor (SSRI)
Primary Mechanism	Increases dopamine and norepinephrine	Increases serotonin
Main Use	Major Depressive Disorder (MDD), Seasonal Affective Disorder (SAD), Smoking Cessation	Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD)
Effect on Energy/Motivation	Often increases energy and motivation	May cause fatigue or drowsiness
Sexual Side Effects	Low incidence, can counteract Lexapro's side effects	Higher incidence, including reduced libido and dysfunction
Effect on Anxiety	Can sometimes worsen anxiety, especially at first	Generally effective at reducing anxiety symptoms
Weight Effects	Often neutral or causes slight weight loss	Can be associated with weight gain

Making an Informed Decision

Deciding to combine Wellbutrin and Lexapro should be a joint decision between you and your healthcare provider, based on your specific symptoms, treatment history, and tolerance for side effects. The best approach is individualized, weighing the benefits against the risks. For example, adding Wellbutrin might be suitable if you're on Lexapro and experiencing fatigue, low motivation, and sexual side effects. Regular follow-up is essential to monitor progress and manage side effects.

Conclusion

So, do Wellbutrin and Lexapro work well together? For many with treatment-resistant depression, this combination is effective, targeting different neurotransmitter systems for a more comprehensive approach to mood and energy-related symptoms. It can also help alleviate some bothersome side effects of Lexapro, like sexual dysfunction. However, it's not universally suitable and carries risks, including serotonin syndrome and increased seizure risk. Under a doctor's supervision, this tailored combination can improve outcomes for those who haven't found sufficient relief from a single medication.

For more information on the efficacy of combination antidepressant therapy, see research published in the National Institutes of Health.

Frequently Asked Questions

No, combining these medications should only be done under strict medical supervision due to the risks of serious side effects and interactions. Always follow your doctor's guidance.

Benefits include broader symptom control, improved energy and motivation, and counteracting common sexual side effects and fatigue associated with Lexapro.

Serotonin syndrome is a potentially life-threatening condition from excessive serotonin. Although rare with this combination, Wellbutrin can indirectly increase serotonin risk, especially at high doses or with other serotonergic drugs.

Yes, combining antidepressants can lower the seizure threshold, increasing the risk, particularly at high doses or in patients with a history of seizures.

Lexapro primarily addresses mood and anxiety via serotonin, while Wellbutrin targets energy, motivation, and focus through dopamine and norepinephrine, providing more complete symptom coverage.

Common side effects can include insomnia, anxiety, dry mouth, sweating, and nausea, some of which may be intensified by the combination. These often diminish over time.

While individual response varies, it typically takes several weeks for patients to see a noticeable impact on their symptoms, similar to single-drug therapy. Your doctor will monitor your progress.