March 2023: Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression
The issue
Treatment‑resistant depression (TRD) — failure to improve after two adequate antidepressant trials — is common in late life and worsens well‑being, function, and cognition. A large OPTIMUM trial asked whether adding a new drug (augmentation) or switching drugs works better.
What do I need to know?
In 619 adults ≥ 60, augmenting the current antidepressant with aripiprazole lifted psychological well‑being more than switching to bupropion, and somewhat more than adding bupropion. Well‑being rose 4.83 vs 2.04 points, and remission occurred in 29 % vs 19 %. Falls were common with all options but highest when bupropion was added (0.55 vs 0.33 falls per patient). Among 248 patients who still had symptoms, lithium augmentation and switching to nortriptyline gave similar benefits and safety, with remission in roughly 19–22 %. Overall, aripiprazole augmentation offered the best balance between mood gain and fall risk, while bupropion augmentation demands extra caution for balance problems.
Potential risk of treatment‑resistant depression
First antidepressant started, but symptoms persist after 4–6 weeks.
Recommended Actions
Track PHQ‑9 or Geriatric Depression Scale scores at every visit.
Confirm adherence and adjust to a therapeutic dose.
Screen for medical or psychological factors that blunt response (pain, thyroid, anxiety, bereavement).
Imminent risk of treatment‑resistant depression
No remission after one adequate drug trial.
Recommended Actions
Discuss augmentation versus switch; evidence favors adding low‑dose aripiprazole (2–5 mg up to 15 mg).
If fall risk is high, avoid bupropion augmentation or add balance precautions.
Reassess mood, gait, and blood pressure within 4 weeks of any change.
Confirmed treatment‑resistant depression
No remission after two or more adequate trials.
Recommended Actions
If aripiprazole or bupropion augmentation fails, consider lithium augmentation (target serum 0.6 mmol/L) or switch to nortriptyline, with ECG and renal checks.
Refer for psychiatric consultation and explore neurostimulation (ECT, TMS) when severe or suicidal.
Monitor falls closely; review medications that worsen balance or cause orthostasis.
What can I do?
Ask the doctor, “Am I at potential, imminent, or confirmed risk, and which strategy—add or switch—fits me best?” Keep a weekly mood and fall diary. If starting aripiprazole, note any agitation or stiffness and report promptly. For bupropion, practice fall‑prevention measures (grab bars, night lighting). Should lithium be advised, arrange regular blood draws and watch for tremor or thirst. Family members can help track pills, accompany appointments, and ensure the home is safe from fall hazards.
