Effectiveness of rTMS vs. Pharmacotherapy in Late-Life Treatment-Resistant Depression: An Observational Study of Individual Participant Data From Two Randomized Clinical Trials

Published October 14, 2026. In an adjusted analysis of two earlier trials involving adults age 60 or older, rTMS was associated with lower depression scores at 10 weeks than three medication strategies. The comparison was not randomized between treatment types, so it supports a careful discussion of options rather than proving that rTMS is superior for every older adult.

Adler E, Blumberger DM, Lenze EJ, Brown PJ, Karp JF, Lavretsky H, Rhee TG, Mulsant BH, Kaster TS.
American Journal of Psychiatry · Publication date: 2026-10-14
Added to site: 2026-10-28
DOI: 10.1176/appi.ajp.20260398

Published October 14, 2026. Added to Neurofeedback.com October 28, 2026 after comparison with the private evidence reserve. This is a historical addition within the site's selection workflow, not a newly published October 28 study.

Modalities

Repetitive transcranial magnetic stimulation, Bilateral rTMS, Pharmacotherapy

Clinical focus

Late-life depression, Treatment-resistant depression, Comparative effectiveness

Population

Adults age 60 or older with late-life treatment-resistant depression who participated in the FOUR-D rTMS trial or OPTIMUM pharmacotherapy trial

Sample

758 eligible participants: 160 from FOUR-D and 598 from OPTIMUM, as reported by the linked institutional appraisal

Intervention / method

Once-daily bilateral rTMS for four to six weeks was compared indirectly with aripiprazole augmentation, bupropion augmentation and switching to bupropion; the primary outcome was MADRS depression severity 10 weeks after treatment initiation

Comparator

Three medication strategies drawn from a separate randomized trial; participants were not randomized between rTMS and medication

Clinician summary

Adjusted 10-week MADRS differences favored rTMS by 4.16 points versus aripiprazole augmentation, 6.08 versus bupropion augmentation and 6.36 versus switching to bupropion. Adjusted response odds also favored rTMS, but confidence intervals were wide. Remission comparisons were not statistically significant in the institutional appraisal, and headache occurred significantly more often with rTMS.

How to interpret the findings

This was an observational comparison across two different randomized trials, not a head-to-head trial that randomized participants between stimulation and medication. Restriction, overlap weighting and regression adjustment address measured differences but cannot remove unmeasured confounding, expectancy effects or all design differences. The analysis covered specific bilateral rTMS and medication strategies in adults age 60 or older with treatment-resistant depression; it should not be generalized to every TMS protocol, medication or patient. The checked abstract did not provide full event counts for headache, all adverse effects, attrition or durability beyond 10 weeks.

Equipment and disclosures

The abstract identifies once-daily bilateral rTMS but does not establish comparative performance for a specific commercial system. No equipment is attributed to BrainMaster, BrainsWay, MagVenture or another vendor.

FOUR-D was funded by the Canadian Institutes of Health Research. OPTIMUM was funded by the Patient-Centered Outcomes Research Institute and supported by the National Institute of Mental Health. The publisher record lists multiple author relationships, including investigator-initiated or sponsor-initiated study support and in-kind equipment from BrainsWay and MagVenture, scientific-adviser work for Sooma Medical, and other research, consulting and advisory relationships. No correction, retraction or expression-of-concern relation appeared in the checked PubMed and publisher records; this is a bounded check. AI-assisted source review.

Related evidence

Compare findings from the same clinical area, including mixed results.

• Latent class modeling of repetitive transcranial magnetic stimulation response trajectories in treatment-resistant depression · Positive with limitations
• Efficacy of Non‐Invasive Brain Stimulation on the Treatment of Late Life Depression: A Systematic Review and Network Meta‐Analysis · Positive with limitations
• Right putaminal gray matter change tracks psychomotor recovery after accelerated iTBS in melancholic treatment-resistant depression · Mixed
• Clinical outcomes following five-day accelerated intermittent theta burst stimulation for treatment-resistant depression in routine clinical practice: A prospective naturalistic cohort study · Positive with limitations
• Excitation-Inhibition Balance and Fronto-Limbic Connectivity Distinguish TMS Treatment Outcomes in Refractory Depression · Positive with limitations
• Use of neurostimulation in patients with treatment-resistant depression: current options and future directions. · Positive with limitations
• Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression. · Positive with limitations