A three-month follow-up pilot study on accelerated intermittent Theta Burst Stimulation for bipolar depression

BackgroundApproximately 25% of all patients with bipolar disorder are considered treatment-resistant. Accelerated intermittent Theta Burst Stimulation (aiTBS) is an innovative form of repetitive transcranial magnetic stimulation (rTMS), delivering bursts of stimulation at theta wave frequencies, which are believed to enhance synaptic plasticity. This pilot study aimed to explore the safety, tolerability, and preliminary efficacy of aiTBS in individuals with treatment-resistant bipolar depression (TRBD). MethodsThis open-label pilot study (Overview of Medical Research in the Netherlands (OMON): NL-OMON53634) included eight patients diagnosed with TRBD. Participants received eight daily sessions of intermittent Theta Burst Stimulation (iTBS) over five consecutive days, with 50-minute intervals between sessions. Stimulation targeted the left dorsolateral prefrontal cortex (dlPFC) using the BeamF3 targeting method. Primary outcomes were safety, tolerability, and efficacy. Safety was assessed by recording (serious) adverse events; tolerability was evaluated through side effect reports and dropout rates. Efficacy was measured as the mean reduction in depression severity, as assessed by the 17-item Hamilton Depression Rating Scale (HDRS-17). ResultsaiTBS was well tolerated and no SAEs occurred during the treatment week. Most observed adverse events were discomfort at the site of stimulation and fatigue [7/8, 87.5%]. No treatment-emergent [hypo]mania was observed during intervention week or during the follow-up. One patient experienced hypomanic symptoms [YMRS=13] at the 3 month follow-up visit. The mean HDRS decreased from 22.9 [SD=4.4] at baseline to 16.6 [SD=4.2] at day 3 of treatment [difference= -6.3 (95% CI, 1.6 - 10.9); 27.3% improvement, p=0.01*], decreased significantly to 12.3 [SD=4.1] at day 5 [difference= -10.1 (95% CI, 2.2 - 18.1); 44.3% improvement, p=0.02*], decreased significantly to 11.1 [SD=3.8] at week 2 of FU [difference= -11.8 (95% CI, 4.5 - 19.0); 51.4% improvement, p=0.004**] and decreased significantly to 13.5 [SD=3.9] at week 4 of FU [difference= -9.4 (95% CI, 1.0 - 17.7); 41.0% improvement, p=0.03*]. ConclusionThis study extends on the previous of rapid antidepressant effects, safety and tolerability of aiTBS in patients with TRBD. We suggest future RCTs to investigate maintenance aiTBS or tapering studies, to possibly prolongate the antidepressant effect. Conflict of Interest declarationThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.