Bilateral Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Regions for Late-Life Depression: A Randomized, Sham-Controlled Clinical Trial

OBJECTIVE: The objective of this study was to assess the efficacy of theta-burst stimulation (TBS) in treating late-life depression. METHODS: A triple-blind, sham-controlled randomized clinical trial was performed. The study included participants age 60 and older with a diagnosis of moderate to severe major depressive disorder who were not using antidepressants. Exclusion criteria included other psychiatric disorders, neurological disorders, and contraindications to TBS. TBS was administered bilaterally, with intermittent TBS on the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS on the right DLPFC, with 1,800 pulses at each side. Participants underwent 20 daily sessions of active or sham TBS over 20 consecutive weekdays and one additional session during weeks 6, 8, and 12 (totaling 23 sessions). RESULTS: A total of 108 participants (mean age, 67 years) were enrolled and underwent either active or sham TBS. In an intention-to-treat analysis, there was no significant difference between groups at week 6 in mean reduction in Hamilton Depression Rating Scale (HAM-D) score (mean difference, -1.65, 95% CI=-3.38, 0.08). By week 12, active TBS was associated with a significantly greater reduction in HAM-D score compared to sham (mean difference, -1.89, 95% CI=-3.75, -0.03), with response rates of 52% in the active group and 33% in the sham group. Linear mixed models analyzing HAM-D score did not show a statistically significant greater reduction in the active TBS group compared to the sham group at week 6 (Cohen's d=-0.36, 95% CI=-0.74, 0.01). CONCLUSIONS: The active TBS group did not have a statistically significant greater reduction in HAM-D scores compared to the sham group at week 6. By week 12, however, active TBS was superior to sham stimulation in reducing depressive symptoms in patients with late-life depression, suggesting TBS as a possible treatment option for this population.