What is the best treatment for Major Depressive Disorder (MDD) when the patient is already on Sertraline (Selective Serotonin Reuptake Inhibitor, SSRI)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

For patients with Major Depressive Disorder (MDD) who are already on Sertraline, the best treatment approach would be to consider augmenting with bupropion (150-300mg daily) if the patient has been on an optimized dose of sertraline for at least 4-6 weeks without adequate response. This approach is supported by low-quality evidence from one trial 1 that showed augmenting with bupropion decreases depression severity more than augmentation with buspirone. When considering treatment adjustments, it's essential to prioritize the patient's quality of life, morbidity, and mortality.

Key Considerations

  • Before making any changes, ensure the patient's current sertraline dosage is optimized, typically up to 200mg daily if tolerated.
  • If augmentation with bupropion is not effective, consider switching to another SSRI or venlafaxine XR, although the evidence for switching strategies is mostly low-quality 1.
  • Psychotherapy, particularly cognitive behavioral therapy (CBT), should be added if not already in place, as it can be an effective adjunct to pharmacologic treatment.
  • Regular monitoring for side effects, suicidal ideation, and treatment response using standardized measures like the PHQ-9 is essential throughout treatment adjustments 1.

Treatment-Resistant Cases

For treatment-resistant cases, consider consultation with psychiatry for potential treatments like ketamine, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT), although these options are typically reserved for severe or refractory cases. The goal of treatment should always be to improve the patient's quality of life, reduce morbidity, and minimize mortality risk.

From the Research

Treatment Options for Major Depressive Disorder (MDD) with Inadequate Response to Sertraline

  • Aripiprazole augmentation has been shown to be an effective treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy, including sertraline 2, 3.
  • The combination of aripiprazole and sertraline has been found to be well-tolerated and associated with significant improvements in depressive symptoms, with a two-fold higher remission rate than adjunctive placebo 2.
  • Bupropion, a dopamine-noradrenaline reuptake inhibitor, is an effective antidepressant that can be used in combination with SSRIs, including sertraline, to enhance antidepressant response and reduce sexual side effects 4, 5.
  • However, the efficacy and safety of bupropion in combination with sertraline specifically have not been extensively studied, and more research is needed to determine the optimal dose and duration of treatment 5.

Efficacy and Safety of Treatment Options

  • Aripiprazole augmentation has been found to be associated with a significant improvement in depressive symptoms, with a mean change in MADRS total score of -10.1 compared to -6.4 for adjunctive placebo 2.
  • The combination of aripiprazole and sertraline has been found to be well-tolerated, with low rates of discontinuations due to adverse events and no notable issues in safety assessments 3.
  • Bupropion has been found to be generally well-tolerated, with a similar tolerability profile to SSRIs, but with less somnolence and sexual dysfunction 4.

Considerations for Treatment

  • Patients with MDD who do not respond adequately to standard antidepressant monotherapy, including sertraline, may benefit from aripiprazole augmentation or the addition of bupropion to their treatment regimen 2, 3, 5.
  • The choice of treatment should be based on individual patient needs and medical history, and should be closely monitored for efficacy and safety 2, 3.

Related Questions

What type of depression does the combination of Wellbutrin (bupropion) and Mirtazapine treat?
What are the benefits of starting someone on Wellbutrin (bupropion) in conjunction with a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) for treatment-resistant depression?
What are the options for augmenting Wellbutrin (bupropion) in patients who have not responded adequately to treatment?
What is the next best step for a 24-year-old female with anxiety, depression, and disordered eating thoughts, who had an allergic reaction to Wellbutrin (bupropion) and minimal efficacy with Fluoxetine (fluoxetine)?
What are the next steps in treatment for a patient on Wellbutrin (bupropion) ER 300mg daily for Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and Attention Deficit Hyperactivity Disorder (ADHD)?
How do you diagnose pyloric stenosis in an infant?
What is the greatest risk factor for frostbite in a 54-year-old man with diabetes (Diabetes Mellitus), hyperlipidemia, hypertension, and hypothyroidism, who develops redness and stinging of the fingers and toes after working outdoors for several hours during a winter storm?
What is the best medication for an elderly man with treatment-resistant major depressive disorder (MDD) on Sertraline (sertraline)?
What is mallet finger, its causes, and treatment options?
What is the most likely finding for cataracts in a 2-year-old woman with blurry vision, glare, and a 40 pack-year history of cigarette smoking, with well-controlled essential hypertension on hydrochlorothiazide (Hydrochlorothiazide) and allergic rhinitis managed with antihistamines?
What are the typical presentations of Multiple Sclerosis (MS) in a 50-year-old female?

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.