Connectivity- and frequency-individualized accelerated intermittent theta burst stimulation in treatment-resistant depression: A randomized controlled trial.

Accelerated intermittent theta burst stimulation (aiTBS) is an effective neuromodulatory intervention for treatment resistant depression (TRD). aiTBS delivers repetitive transcranial magnetic stimulation sessions over a compressed timeframe and can be individualized to specific locations using resting-state functional magnetic resonance imaging (rs-fMRI) to target pathological cortical networks or individualized in time using electroencephalography (EEG) to determine optimal participant-specific stimulation frequencies. In this randomized, placebo-controlled trial, we tested these forms of personalization against sham stimulation. Fifty-one patients with TRD were randomized to one of three arms; 43 completed the protocol per pre-specified criteria and assigned to one of three arms: (1) fMRI-connectivity-individualized aiTBS; (2) frequency- and connectivity-individualized aiTBS; or (3) sham aiTBS. Participants received 10 aiTBS sessions per day for five consecutive days with clinical assessments at baseline, and 1 and 4 weeks post-treatment. The primary outcome was change in depression severity on the Montgomery-Åsberg Depression Rating Scale from baseline to 1 week post-treatment. Anhedonia severity measured with the Dimensional Anhedonia Rating Scale was a secondary outcome. No significant differences were observed between active and sham arms on primary MADRS or secondary DARS endpoints for either the intent-to-treat or per-protocol sample. Remission and response rates also did not differ between arms. aiTBS individualized using either rs-fMRI or EEG and rs-fMRI failed to yield significant antidepressant benefits over sham stimulation, with relatively muted overall therapeutic benefits, underscoring the need for further clinical trials evaluating the efficacy of personalized aiTBS in TRD.