Double the dose, double the impact? Effects of iTBS on salivary cortisol in stressed healthy volunteers

There is a growing interest in applying double-dose repetitive transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for stress-related psychiatric disorders. Such stimulation protocols may shorten the treatment duration and may result in faster symptom improvement. Currently, theta-burst stimulation (TBS) protocols have gained attention because of their significantly reduced treatment duration, compared to conventional rTMS. However, the effect of one or twice daily rTMS sessions remains unclear in relation to stress. Using a two-period cross-over design, we examined the impact of double-dosed intermittent (TBS) over the left dorsolateral prefrontal cortex on stress responses (salivary cortisol) in thirty-eight healthy participants after being stressed by a validated psychosocial stress task: the Trier Social Stress Test. After the first active iTBS session, as contrasted to sham, no differential effects on salivary output were observed. However, after the second active session, there was a significantly smaller decrease of salivary cortisol concentrations in the active iTBS condition compared to sham. Our results suggest that double-dosed iTBS after being stressed might differently affect stress recovery compared to a single session of iTBS.