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

OBJECTIVE: The authors compared the effectiveness and tolerability of repetitive transcranial magnetic stimulation (rTMS) versus pharmacotherapy augmentation and switching strategies in older adults with late-life treatment-resistant depression (LL-TRD). METHODS: This observational study used individual participant data from 758 participants age 60 or older with LL-TRD from two randomized controlled trials: an rTMS trial of once-daily bilateral treatment for 4-6 weeks, and a pharmacotherapy trial comparing aripiprazole augmentation, bupropion augmentation, and switch to bupropion. Restriction, propensity score weighting, and regression adjustment were used to account for differences in trial design and eligibility criteria. The primary outcome was the Montgomery-Åsberg Depression Rating Scale (MADRS) 10 weeks after treatment initiation. RESULTS: After accounting for differences in participant characteristics, rTMS was associated with lower MADRS scores than aripiprazole augmentation (difference: 4.16 points, 95% CI=2.32, 6.00), bupropion augmentation (difference: 6.08 points, 95% CI=4.06, 8.09), and switch to bupropion (difference: 6.36 points, 95% CI=4.55, 8.17). rTMS was also associated with a higher response rate (defined as reduction ≥50% in MADRS score from baseline to week 10) than aripiprazole augmentation (adjusted odds ratio [AOR]=3.83, 95% CI=1.08, 13.56), bupropion augmentation (AOR=4.87, 95% CI=1.15, 20.68), and switch to bupropion (AOR=4.02, 95% CI=1.12, 14.47). Participants who received rTMS were significantly more likely to experience headache than those who received pharmacotherapy. CONCLUSIONS: This analysis suggests that rTMS for LL-TRD may be superior to pharmacotherapy and supports the use of rTMS earlier in the treatment algorithms for LL-TRD.