Treatment-resistant depression (TRD) is not uncommon in older people. Brain stimulation, such as 4-6 weeks of repetitive transcranial magnetic stimulation (rTMS) or theta burst stimulation (TBS) targeting the left dorsolateral prefrontal cortex, has been evidenced as an essential intervention for adult TRD and also documented in the current international treatment guideline. In 2018, Taiwan Food and Drug Administration cleared the rTMS as a treatment option for TRD and now rTMS is still a treatment at their own expense in Taiwan. Additionally, prolonged intermittent TBS (piTBS) protocol has been proven its similar antidepressant efficacy as standard 4-6 weeks rTMS/iTBS in adult TRD, but in a shorter treatment course of 2 weeks. For older adults with depression, 4-6 weeks of treatment course may burden their caregiver due to their limited ambulation and transportation ability. However, hitherto there was no study to investigate the antidepressant efficacy of left-sided prefrontal piTBS in treating older TRD.

A chart review was performed at a single Taiwan hospital from 2018 to 2020. 17-items Hamilton Depression Rating Scale (HDRS-17) was measured before and after the piTBS intervention. Maudsley Staging Method was used for the depression treatment refractoriness.

We identified 23 old adults with TRD (mean [SD] age, 66.0[5.2]; 78% female) who underwent 10-20 sessions of daily piTBS (1800 pulses/session; 10sessions, n=18, 15sessions,n=4, 20session,n=1). On continuous outcomes, mean(SD) HDRS-17 total scores improved from 20.5(6.62) to 11.8(7.7) after receiving piTBS intervention. The mean percent improvement of HDRS-17 was 46.0%±29.4%. Dichotomous outcomes showed response rate of 43.5% and remission rate of 34.8%. No seizures or other serious adverse events were noted, and no premature discontinuation was noted.

This study is the largest study demonstrating the piTBS protocol provides a comparable reduction in depression symptoms in older adults with TRD, similar to the effectiveness in adult TRD and the efficacy of standard sequential bilateral rTMS/iTBS in older TRD in the FOUR-D trial. Regarding desirable efficiency and effectiveness, piTBS may be an optimal form of rTMS in treating older adults with TRD. Further large comparative effectiveness trials with standard iTBS or high-frequency rTMS in this population are warranted.