Can you take Lexapro (escitalopram), Wellbutrin (bupropion), and Mirtazapine simultaneously?

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From the Guidelines

It is possible to take Lexapro (escitalopram), Wellbutrin (bupropion), and Mirtazapine simultaneously, but this combination should only be used under close medical supervision. This three-medication regimen is sometimes prescribed for patients with treatment-resistant depression who haven't responded adequately to single or dual medication approaches. Each medication works through different mechanisms: Lexapro is a selective serotonin reuptake inhibitor (SSRI), Wellbutrin affects dopamine and norepinephrine, and Mirtazapine works on multiple neurotransmitter systems. When combined, they can potentially address depression more comprehensively. However, this combination carries increased risks of side effects and drug interactions, including potential serotonin syndrome (a dangerous condition with symptoms like confusion, rapid heart rate, and high blood pressure) 1. Some key points to consider when taking this combination include:

  • Dosing must be carefully managed, typically starting with lower doses of each medication before gradually increasing as tolerated.
  • Regular monitoring for side effects, blood pressure changes, and mood shifts is essential.
  • Anyone taking this combination should immediately report unusual symptoms to their healthcare provider and should never adjust dosages or stop medications without medical guidance. According to a study published in the American Family Physician in 2015 1, preferred agents for depression treatment include citalopram, escitalopram (Lexapro), bupropion, mirtazapine, venlafaxine, and sertraline, which are considered appropriate due to their favorable adverse effect profiles. Key considerations for the medications in question are:
  • Escitalopram (Lexapro) has a dosage range of 10 to 20 mg per day, with no recommended decrease in dose for renal or hepatic disease 1.
  • Bupropion SR (Wellbutrin SR) has a dosage range of 100 to 400 mg per day, with recommended dose decreases in both renal and hepatic disease 1.
  • Mirtazapine (Remeron) has a dosage range of 15 to 45 mg per day, with consideration for dose decrease in renal or hepatic disease 1.

From the Research

Combination of Lexapro, Wellbutrin, and Mirtazapine

The combination of Lexapro (escitalopram), Wellbutrin (bupropion), and Mirtazapine is a complex regimen that requires careful consideration of potential interactions and side effects.

  • Serotonin Syndrome Risk: The use of multiple serotonergic agents, such as SSRIs (e.g., Lexapro), bupropion, and mirtazapine, increases the risk of serotonin syndrome, a potentially life-threatening condition 2, 3, 4.
  • Pharmacological Interactions: Bupropion inhibits the reuptake of noradrenaline and dopamine, with milder effects on serotonergic activity. However, its combination with SSRIs can increase the risk of serotonin syndrome 2.
  • Mirtazapine's Mechanism: Mirtazapine blocks presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors, which can contribute to the risk of serotonin syndrome when combined with other serotonergic agents 5, 6.
  • Clinical Implications: The combination of these medications may require close monitoring for signs of serotonin syndrome, such as agitation, confusion, and changes in vital signs.

Key Considerations

  • Dosing and Titration: Careful dosing and titration of each medication are crucial to minimize the risk of adverse interactions.
  • Patient Monitoring: Regular monitoring of patients taking this combination is essential to detect early signs of serotonin syndrome or other adverse effects.
  • Alternative Treatments: In some cases, alternative treatment regimens may be necessary to minimize the risk of adverse interactions.

Evidence-Based Recommendations

Based on the available evidence, it is essential to approach the combination of Lexapro, Wellbutrin, and Mirtazapine with caution, considering the potential risks and benefits for each patient 5, 2, 3, 4, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Severe serotonin syndrome induced by mirtazapine monotherapy.

The Annals of pharmacotherapy, 2002

Research

Mirtazapine, an antidepressant.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 1998

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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