Ask AI
Back Back
Switching vs Augmenting in MDD
Navigating MDD Management: When to Switch, Augment, or Stay the Course

Released: November 11, 2025

Jason Tucciarone
Jason Tucciarone, MD, PhD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Assess and aim for remission, not just response: an adequate trial of an antidepressant means 4-8 weeks at a therapeutic dose. Monitor symptoms every 2-4 weeks using validated tools like the PHQ-9. Target remission (PHQ-9 score ≤4), keeping in mind that some residual symptoms may persist even in remission.
  • Individualize switch vs augment strategies: after 6-8 weeks, if the patient has a partial response (25%-50% improvement), consider dose optimization, augmentation, or adding psychotherapy. If there is minimal, no response, or intolerable side effects, then switch within class first (eg, SSRI to SSRI) before trying a different class (eg, SNRI).
  • Tailor augmentation and psychotherapy to symptom profile: no single augmentation agent is superior; selection should be based on specific symptoms and patient characteristics (eg, mirtazapine for insomnia, bupropion for fatigue or sexual side effects, low-dose lithium for suicidality). Psychotherapy should be integrated early and matched to patient needs, with strong evidence supporting combined treatment for optimal outcomes.

What counts as an “adequate trial” (dose + duration), and how much early improvement (eg, ~25% at 2-4 weeks) should trigger switching vs augmenting?
The American Psychiatric Association considers an adequate trial as 4-8 weeks at a therapeutic dose of the antidepressant. Healthcare professionals (HCPs) in the primary care setting will want to assess baseline depression ratings with a standard rating scale (we favor the PHQ-9 for this purpose). In addition, HCPs should screen for suicidal symptoms, substance use, past medication trials, and treatment adherence. Begin your antidepressant and monitor closely every 2-4 weeks for tolerability, side effects, and efficacy. Titrate your medication to a therapeutic dose (there are many online references including from the American Academy of Family Physicians). We typically make dose adjustments every 2 weeks, but this can be extended or shortened depending on patient tolerability and preference.

A key point to emphasize is that HCPs should try and target symptom remission and not just response. For us, functional recovery equates to a score of 4 or less on the PHQ-9. Another key point is that remission does NOT equate to complete absence of symptoms and often patients will have persistent residual symptoms. For example, many continue to have sleep disruptions or low energy levels. Overall, the goal for primary care HCPs should be a reduction of symptoms significant enough for the patient to have improved functioning and accomplishment of individual life goals. This can only be teased out by assessing the patient’s clinical state and goal setting of therapy between the HCP and patient.

Once the patient is on a stable, therapeutic dose of a given antidepressant, the HCP should titrate and reassess every 2-4 weeks. If there is a partial response (25%-50% symptom reduction) after 6-8 weeks at a therapeutic dose, one should consider optimizing the dose, adding an augmentation agent, and supplementing with psychotherapy. If there is less than a partial response, no response at all, or intolerable side effects, it is worth switching to a new medication. I typically first switch to another medication within class (ie, from one SSRI to another), before transitioning to a new medication class (ie, SNRI).

What are the best supported pharmacologic augmentation options (eg, bupropion, lithium, mirtazapine, second-generation antipsychotics), and how do you choose among them?
If the patient has a partial response at adequate therapeutic dose, augmentation is a good strategy. Overall, no augmentation agent has been proven to be superior to others and should be tailored to individual patient characteristics and symptom profile. For example, if the patient has insomnia and lack of appetite, an augmentation agent such as mirtazapine dosed in the evening would be appropriate. If the patient has fatigue and is experiencing sexual side effects from an antidepressant, bupropion is appropriate. There are good clinical data that low-dose second-generation antipsychotics, such as aripiprazole, risperidone, cariprazine, lumateperone, and quetiapine, have high efficacy in geriatric populations but do not need to be exclusively targeted to this patient population. If there is prominent suicidal ideation, low-dose lithium (less than 600 mg daily) can be highly effective. As always, side effects, tolerance, and adherence should be closely monitored, placing special emphasis on metabolic, motor, and drug interactions.

When and how should evidence-based psychotherapy (eg, cognitive behavioral therapy) be added to a partial pharmacologic response?
The short answer is always. There is very strong evidence that therapy plus medication has higher efficacy than either one alone. This could even begin at treatment initiation. No single therapeutic modality is superior to another. Cognitive behavioral therapy is time limited and a gold standard for depression and anxiety. Dialectical behavioral therapy is very efficacious for emotional regulation in those that have suicidal ideation and self-harming tendencies. Psychodynamic psychotherapy has much evidence for durable long-term efficacy as well. I believe psychological healing often comes from 2 minds rather than 1!

Continue

Poll

1.

When managing a patient with partial response (25%-50% improvement) after 6-8 weeks on a therapeutic dose of an antidepressant, what is your most common next step?

Submit