What is the recommended add-on therapy for escitalopram (Lexapro) 20 milligrams daily for treatment-resistant severe major depressive disorder?

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Last updated: May 22, 2025View editorial policy

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From the Research

For persistent severe depression not adequately responding to Lexapro 20mg daily, adding aripiprazole (Abilify) at 2-5mg daily is often recommended, as evidenced by a study published in 2009 1. This combination works well because aripiprazole targets different neurotransmitters (dopamine) than Lexapro (serotonin), providing complementary effects. Some key points to consider when adding aripiprazole to Lexapro include:

  • Starting with a low dose of aripiprazole, such as 2mg daily, and gradually increasing as needed and tolerated
  • Monitoring for potential side effects, such as akathisia, and adjusting the dose or adding other medications as needed
  • Regular follow-up with a healthcare provider to assess effectiveness and adjust treatment as needed Alternatively, other add-on options may be considered, such as bupropion (Wellbutrin) or quetiapine (Seroquel), especially if symptoms include anxiety or sleep disturbances. Combining medication with psychotherapy, particularly cognitive behavioral therapy, often yields better results than medication alone. It's essential to weigh the potential benefits and risks of each add-on option and to prioritize the patient's specific needs and circumstances when making treatment decisions, as supported by the review of escitalopram's efficacy and safety published in 2012 2.

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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