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A 48-year-old man with major depressive disorder has completed two adequate antidepressant trials, fluoxetine 60 mg for 10 weeks and venlafaxine XR 225 mg for 8 weeks, with less than 25% improvement in symptoms. His current PHQ-9 score is 19. He has no history of bipolar disorder, no psychotic features, and his renal function and thyroid panel are within normal limits. He is currently taking venlafaxine XR 225 mg daily. The PMHNP is considering augmentation. Which augmentation strategy has the strongest evidence base for treatment-resistant depression in this clinical scenario?
Explanation
For treatment-resistant depression after two adequate trials, the top-tier augmentation strategies are lithium, thyroid hormone (T3), and atypical antipsychotics (aripiprazole, quetiapine, brexpiprazole). Among these, lithium has the longest and most robust evidence base. Renal and thyroid function should always be confirmed before initiating lithium.
Key Takeaway
Lithium augmentation is one of the most evidence-supported strategies for treatment-resistant depression and should be considered after two failed adequate antidepressant trials.