Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters.

Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided.