Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission?

- Accelerated iTBS treatment was found to be safe and well tolerated.
- Given that all TRD patients experienced clinical improvement to some extent suggests that such accelerated iTBS protocols may be prone to stronger placebo effects.
- Although only a modest part of our TRD patients responded immediate after the two-week iTBS treatment protocol, the follow-up assessment showed meaningful response increases, close to remission. These findings point to delayed positive clinical effects after accelerated iTBS treatment.

Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.