Can bupropion (Wellbutrin) and escitalopram (Lexapro) be taken together?

Can Wellbutrin and Lexapro Be Taken Together?

Yes, bupropion (Wellbutrin) and escitalopram (Lexapro) can be safely taken together, and this combination is commonly used in clinical practice for treatment-resistant depression. The combination addresses depression through complementary mechanisms—escitalopram affects serotonin pathways while bupropion works via noradrenergic and dopaminergic pathways. 1

Evidence Supporting Combination Therapy

The combination of escitalopram and bupropion demonstrates superior efficacy compared to monotherapy in patients who have failed initial SSRI treatment. In clinical studies, augmenting SSRIs with bupropion decreases depression severity more effectively than other augmentation strategies like buspirone, with significantly lower discontinuation rates due to adverse events (12.5% vs. 20.6%, P < 0.001). 1

• An open pilot study of 51 outpatients with chronic or recurrent major depressive disorder showed response rates of 62% and remission rates of 50% when treated with the combination of escitalopram and bupropion-SR, which are significantly higher than typical SSRI monotherapy outcomes. 2

• The combination was well tolerated in this study, with only 6% of participants discontinuing due to side effects. 2

• A retrospective review of 27 patients with affective disorders showed that 70% experienced greater symptomatic improvement during combined therapy compared to either agent alone. 3

Dosing Recommendations

Start escitalopram at 10 mg daily, then add bupropion-SR at 150 mg once daily after week 1. 2

• Increase bupropion to 150 mg twice daily after 3 days if tolerated. 1

• Maximum doses are escitalopram 20 mg daily and bupropion 400 mg daily for the SR formulation (or 450 mg daily for XL formulation). 1, 2

• In clinical practice, mean effective doses are escitalopram 18 mg daily and bupropion-SR 327-329 mg daily. 2

Critical Safety Screening Before Starting

Before initiating this combination, verify the patient does not have absolute contraindications to bupropion:

• History of seizure disorders or any condition predisposing to seizures (brain tumor, stroke, head trauma). 1

• Current or recent MAOI use (within 14 days of discontinuation). 1

• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk. 1

• Uncontrolled hypertension, as bupropion can elevate blood pressure and heart rate. 1

• Moderate to severe hepatic or renal impairment requiring dose adjustments. 1

Monitoring Requirements

During the first 1-2 weeks, closely monitor for suicidal ideation, agitation, irritability, or unusual behavioral changes, as the risk of suicide attempts is highest during the initial 1-2 months of antidepressant therapy. This is especially critical for patients younger than 24 years. 1

• Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can cause elevations in both parameters. 1

• Assess for neuropsychiatric adverse effects including agitation, restlessness, and behavioral changes. 1

• Watch for signs of serotonin syndrome during the first 1-2 weeks: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremor, clonus), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis). 1

Expected Timeline for Response

Maintain patients on therapeutic doses for 6-8 weeks before evaluating overall treatment response. Early improvement in energy may be observed with bupropion within the first few weeks, but definitive response assessment should wait until the 6-8 week window. 1

• If adequate response is not achieved by 6-8 weeks at therapeutic doses, consider dose adjustments or adding cognitive-behavioral therapy rather than further medication changes. 1

Clinical Advantages of This Combination

Bupropion may counteract SSRI-induced sexual dysfunction, which occurs significantly less often with bupropion compared to SSRIs like escitalopram and paroxetine. 1

• Bupropion is associated with minimal weight gain or even weight loss, unlike many SSRIs. 1

• The combination is particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia, as bupropion has activating properties. 1

• For patients who smoke, this combination addresses both depression and may assist with smoking cessation. 1

Common Side Effects

The most common adverse effects during combined therapy include:

• Sexual dysfunction (41% of patients). 3
• Insomnia (22%)—administer the second bupropion dose before 3 PM to minimize this risk. 1, 3
• Anergy (15%). 3
• Tremor (11%). 3

Important Contraindication to Combination Therapy

One randomized controlled trial of 245 patients found that starting both medications together as initial treatment did NOT outperform monotherapy with either drug alone in terms of speed or rate of remission. 4 Therefore, the combination is best reserved for patients who have failed an adequate trial (6-8 weeks) of SSRI monotherapy, rather than as first-line treatment. 1

No Washout Period Required

Immediate initiation of escitalopram after stopping bupropion is safe; no washout period is needed because neither drug is a monoamine oxidase inhibitor (MAOI). 1 The 14-day washout requirement applies only to transitions involving MAOIs and does not apply to bupropion-to-escitalopram switches. 1