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Am Fam Physician. 2023;108(3):online

Clinical Question

What is the best pharmacologic approach in adults 60 years and older with treatment-resistant depression?

Bottom Line

There are several takeaways from the trial. Aripiprazole and bupropion augmentation produce similar modest improvements, and both are a reasonable option. Although injurious falls appear to be more common with bupropion, the authors did not report weight gain and hyperglycemia, which are both known adverse effects of aripiprazole. In the second comparison, a switch to nortriptyline seems preferable to lithium augmentation based on the simplicity of dosing and a lower risk of injurious falls. (Level of Evidence = 1b−)


Researchers in the Patient-Centered Outcomes Research Institute–sponsored trial identified adults 60 years and older who had not achieved remission of their depressive symptoms after trials of at least two antidepressants and had a Patient Health Questionnaire-9 (PHQ-9) score of 10 or more (range = 0 to 27). At baseline, patients had a mean age of 69 years, 67% were women, and the mean PHQ-9 score was 16. The primary outcome was patient-reported symptoms based on the Positive Affect and General Life Satisfaction subscales of the National Institutes of Health Toolbox Emotion Battery. Remission was defined as a score of 10 or lower on the Montgomery-Åsberg Depression Rating Scale (MADRS; range = 0 to 60). It was an open-label randomized trial with two phases.

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