Art: Losing Our Annie, Donald Macdonalds
When antidepressants fail in older patients, adding aripiprazole outperforms switching to bupropion
STUDY: Lenze EJ et al, N Engl J Med 2023;388:1067–79
STUDY TYPE: Randomized clinical trial
FUNDING: Patient-Centered Outcomes Research Institute
Background
Here is the largest trial to date of treatment-resistant depression in older adults, with a few surprises.
The Study
The OPTIMUM trial enrolled 619 adults aged 60 and older whose depression had not resolved after two antidepressant trials. The study randomized patients to further treatments in two steps:
STEP 1: Aripiprazole augmentation, bupropion augmentation, or a switch to bupropion for 10 weeks.
If they didn’t respond to step 1, move on to…
STEP 2: Lithium augmentation vs switch to nortriptyline.
The winner in step 1 was aripiprazole augmentation, which improved psychological well-being significantly more than switching to bupropion (difference of 2.79 points on a well-being scale, effect size Cohen’s d = 0.37).
Both augmentation strategies had similar remission rates at 10 weeks: Aripiprazole augmentation (29%), bupropion augmentation (28%), bupropion (19%).
A surprising risk: Bupropion augmentation had the highest fall rate — about 67% more falls than aripiprazole augmentation.
For step 2, the results were inconclusive, with lithium augmentation and nortriptyline roughly equivalent in both effectiveness and safety.
Practice Implications
- The fall risk with bupropion is confirmed in other studies
- Bupropion failed in its only large augmentation trial (unpublished), so its weakness here is not a surprise
- Though aripiprazole appears safe here, its long term risks — tardive dyskinesia, metabolic, cardiac — are concerning
- If you’re using an antipsychotic for augmentation, aripiprazole is a top choice with 1) largest effect size 2) has the most trials involving true treatment resistance 3) and now, best studied in elderly
- However, they did not test lithium vs aripiprazole, and some studies suggest greater response rates to lithium in the elderly
- Start aripiprazole low (2.5 mg) and titrate to response (5-15 mg/day, usually 5 mg)
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- What do you use for treatment resistant depression in the elderly?
- Do you see falls on bupropion? Do you see other risks with aripiprazole that were missed here?
