The tolerability of transcranial electrical stimulation used across extended periods in a naturalistic context by healthy individuals

Transcranial electrical stimulation (tES) is one of the most widely implemented forms of non-invasive neuromodulation in basic and clinical neuroscience. Further, the use of tES by healthy populations for various purposes is growing widespread daily. The effects of tES protocols on the skin and other tissues has remained uncharacterized when used across extended periods of time by healthy individuals. Therefore, we examined the basic safety and tolerability profile of two distinct tES protocols used repeatedly across an extended period of time by healthy subjects and report our findings here for the first time. The safety and tolerability profile previously accumulated regarding extended use of tES in clinical populations is compelling and supports a low-risk or non-significant risk designation. In the present study, we tested the tolerability (safety) and compliance, compared to sham, of two common tES approaches having a current density < 2 mA/cm²; transcranial Direct Current Stimulation (tDCS) or transcranial Pulsed Current Stimulation (tPCS) used by healthy subjects three to five days (17 - 20 minutes per day) per week for up to six weeks in a naturalistic environment. In this study 100 healthy subjects were randomized to one of three treatment groups: tDCS (n = 33), tPCS (n = 30), or sham (n = 37) and blinded to the treatment condition. The tES and sham waveforms were delivered through self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 treatment sessions (636 sham, 623 tDCS, and 646 tPCS sessions) on study volunteers over a six-week period. There were no serious adverse events in any treatment condition. Common side effects were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in active tES treatment arms (tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham treatment arm. Other adverse events had a rarity (< 5% incidence) that could not be statistically distinguished across the treatment groups. Some subjects withdrew early from the study for atypical headache (sham n = 2, tDCS n = 2, and tPCS n = 3), atypical discomfort (sham n = 0, tDCS n = 1, and tPCS n = 1), or atypical skin irritation (sham n = 2, tDCS n = 8, and tPCS n = 1). The compliance (elected sessions completed) for tPCS was significantly greater when compared to sham (p = 0.007). The present study represents the most comprehensive analysis of tES tolerability and safety in healthy subjects to date. Limited to the hardware, electrodes, and protocols tested here, we conclude that repeated use of limited output tES across extended periods, is well tolerated and poses no significant risks to healthy subjects, as previously observed in clinical studies.