Feasibility and Tolerability of Novel Deep Repetitive Transcranial Magnetic Stimulation for Depression in Older Adults: DIVINE Pilot Study

Objectives Major depressive disorder (MDD) is a leading cause of global disability and is notably prevalent in older adults. Deep transcranial magnetic stimulation (dTMS), specifically the H1-coil targeting the lateral prefrontal cortex, is approved for adults with treatment-resistant MDD and has shown promise in seniors. However, substantive proportions do not respond to the H1-coil and other H-coils, targeting different brain regions implicated in MDD, may also offer therapeutic benefits. The current study examined the feasibility and tolerability of the H4-coil and H7-coil designs in seniors with MDD for the first time. Materials and Methods Participants were 21 older adults with moderate-to-severe treatment-resistant MDD randomized to 20 sessions of H4-coil or H7-coil dTMS for four weeks. Primary outcomes were feasibility (protocol completion) and tolerability (frequency of adverse events). Secondary outcomes were depression, anxiety, cognition, sleep, and somatic complaints, and coil differences. Results Intention-to-treat protocol completion rates were 86.8% for the H4-coil and 98% for the H7-coil. Both treatments were generally well-tolerated with low rates of AEs and no evidence of negative cognitive effects. There was a significant reduction in depression (F(4,68) = 46.54, p < 0.0000001, η2 = 0.73), but no significant coil differences. Both treatments also led to significant reductions in anxiety and somatic complaints. Conclusion This study provides evidence supporting the feasibility and tolerability of the H4-coil and H7-coil in seniors with MDD, with promising evidence of therapeutic benefits. The findings support future sham-controlled designs to formally evaluate clinical efficacy. Clinical Trial Registration The Clinicaltrials.gov registration number for the study is NCT05855850.