What is the most appropriate medication to add to a patient's current sertraline (selective serotonin reuptake inhibitor) regimen for major depressive disorder, given increased somnolence and tiredness?

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Bupropion Addition for SSRI-Induced Somnolence

Add bupropion to this patient's sertraline regimen to address the increased somnolence and hypersomnia. 1

Rationale for Bupropion

Bupropion is the optimal choice in this clinical scenario for several compelling reasons:

  • Activating properties: Bupropion is specifically noted to be "activating" with potential for rapid improvement of energy level, making it ideal for counteracting SSRI-induced somnolence 1
  • Complementary mechanism: As a dopamine-norepinephrine reuptake inhibitor with no serotonergic activity, bupropion provides mechanistic augmentation to sertraline's selective serotonin effects 2, 3
  • Favorable side effect profile: Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs and does not cause the somnolence or weight gain seen with other antidepressants 1
  • Proven efficacy: Bupropion demonstrates equivalent antidepressant efficacy to SSRIs while specifically addressing fatigue and energy deficits 2

Why Not the Other Options

Desipramine is a tricyclic antidepressant that, while activating, carries significant risks of cardiotoxicity, hypotension, anticholinergic effects, and tachycardia—unnecessary risks in a young, otherwise healthy patient 1

Fluoxetine is another SSRI that would not address the somnolence problem and could potentially worsen it, as SSRIs commonly cause somnolence as a class effect 1

Olanzapine is an antipsychotic with potent sedating properties that would dramatically worsen the patient's hypersomnia; it's indicated only when psychotic features are present, which this patient lacks 1

Phenelzine is a monoamine oxidase inhibitor with significant cardiovascular side effects including hypertension and hypotension, plus dangerous dietary restrictions—completely inappropriate as augmentation therapy in this straightforward case 1

Dosing and Administration

  • Initial dose: Start bupropion at 37.5 mg every morning, then increase by 37.5 mg every 3 days 1
  • Target dose: 150 mg twice daily (maximum dose) 1
  • Timing consideration: Give the second dose before 3 p.m. to minimize risk of insomnia 1
  • Contraindications: Do not use in patients with seizure disorders or in agitated patients 1

Monitoring and Follow-up

  • Reassess within 1-2 weeks of initiating bupropion to evaluate response and monitor for adverse effects 1
  • Evaluate therapeutic response at 6-8 weeks: If inadequate response, consider further treatment modifications 1
  • Monitor for seizure risk: While bupropion carries a slightly increased seizure risk, this is dose-dependent and minimized by gradual titration and staying within recommended dosing limits 1
  • Watch for activation: Some patients may experience initial nervousness or insomnia, which typically resolves; timing the second dose appropriately helps prevent this 1

Expected Outcomes

Patients typically experience improvement in energy levels and reduction in somnolence within 2 weeks, with full antidepressant efficacy achieved by 4 weeks of combined therapy 2, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Other Antidepressants.

Handbook of experimental pharmacology, 2019

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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