rTMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation

Abstract Background Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). Objective To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. Methods A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. Results Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. Conclusions Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted.