Brain stimulation could move earlier into treatment planning for older adults whose depression persists despite antidepressants. A new analysis published in the American Journal of Psychiatry found better outcomes with repetitive transcranial magnetic stimulation, or rTMS, than with three medication strategies.
The findings raise a practical question: after unsuccessful medication treatment, when should clinicians discuss a different therapeutic approach?
Medication Changes Remain An Important Crossroads
For persistent depression, treatment decisions can involve adding medication to an existing antidepressant or switching drugs. These choices require balancing potential symptom improvement against tolerability and the demands of continued treatment.
For older patients, the question extends beyond whether another intervention might work. Treatment planning must also consider what a person can realistically sustain and which outcomes matter most to daily life.
A Comparison Built From Individual Patient Data
Researchers analyzed 758 adults aged 60 or older using participant-level data from two randomized trials. One evaluated once-daily bilateral brain stimulation over four to six weeks. The other evaluated aripiprazole augmentation, bupropion augmentation, or switching to bupropion.
The comparison between stimulation and medication was observational. Participants had not been randomly assigned between those treatment categories within one trial.
Researchers used eligibility restrictions, propensity-score weighting, and regression adjustment to improve comparability. These methods help address measured differences but cannot reproduce randomization.
Where TMS Outperforms Medication
At 10 weeks, adjusted depression scores favored rTMS by 4.16 points versus aripiprazole augmentation, 6.08 versus bupropion augmentation, and 6.36 versus switching to bupropion on the Montgomery–Åsberg Depression Rating Scale.
Response, defined as at least a 50% symptom reduction, also favored stimulation. Adjusted response odds were approximately four to five times higher, although confidence intervals were wide. Headache occurred more frequently with rTMS.
Better Outcomes Require Careful Interpretation
Higher response odds should not be read as four to five times the probability of recovery. Odds and probabilities describe different quantities, and response does not necessarily mean remission.
The headline also needs a defined scope. This analysis compares particular strategies in older adults with treatment-resistant depression. It does not establish that stimulation surpasses every antidepressant approach or that medication should be abandoned.
Its clinical value lies in sharpening the next-step discussion after treatment has been unsuccessful.
Magnetic Pulses Target Prefrontal Activity
TMS uses focused magnetic pulses to stimulate cortical neurons. Bilateral treatment targets both sides of the dorsolateral prefrontal cortex, a region involved in depression treatment.
The earlier FOUR-D randomized trial compared conventional bilateral rTMS with bilateral theta burst stimulation, a patterned form of magnetic stimulation. Among 172 older adults, theta burst stimulation met the trial’s noninferiority criterion for symptom improvement while shortening stimulation delivery from approximately 48 minutes to four minutes.
That supporting trial addresses how stimulation can be delivered efficiently. It does not explain biologically why stimulation performed better than medication in the newer comparison. Clinical outcomes alone cannot identify the mechanism responsible for a treatment difference.
A Treatment-Sequence Question Comes Into Focus
The newer analysis is distinctive because it places stimulation alongside recognizable prescribing decisions. For clinicians, that framing connects research more directly to the moment when an existing treatment plan needs revision.
A reasonable implication is to make discussion of stimulation more explicit during shared decision-making. Patients should understand the evidence supporting each option, the uncertainty around individual benefit, and the practical requirements of receiving care.
For clinics, earlier discussion would also require attention to referral pathways and appointment capacity. A potentially effective intervention has limited practical value when patients cannot reach or complete treatment.
The Next Test Is A Direct Comparison
A randomized trial assigning comparable older adults directly to stimulation or medication strategies would provide stronger evidence about treatment sequencing. Longer follow-up could clarify durability, additional treatment needs, and effects on everyday functioning.
For now, the analysis strengthens the rationale for considering rTMS earlier in late-life treatment-resistant depression. It offers a meaningful signal for clinical discussion while leaving the optimal sequence open to further testing.
Citations
- Adler E, et al. Effectiveness Of rTMS Vs. Pharmacotherapy In Late-Life Treatment-Resistant Depression. American Journal of Psychiatry. 2026.
- Blumberger DM, et al. The FOUR-D Randomized Noninferiority Clinical Trial. JAMA Psychiatry. 2022;79:1065–1073.
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