The main objective of this study was to evaluate the effect of left anodal transcranial direct current stimulation (tDCS) on hypothalamic–pituitary–adrenal axis (HPAA) activity in individuals with depression. We conducted a 3-week, randomized, triple-blind pilot trial with 47 participants (dropout rate: 14.89%) randomly assigned to either the tDCS or control group (sham stimulation). Salivary cortisol was used as an HPAA activity marker since cortisol is the effector hormone of the HPAA. The primary outcome was the effect of tDCS on the diurnal cortisol pattern (DCP and area under the curve with respect to ground -AUCg-). Secondary outcomes included tDCS effects on cortisol awakening response (CAR) and cortisol decline (CD), as well as the variation of cortisol concentrations between the initiation of tDCS and 2 weeks later. Intention-to-treat and per-protocol analyses were conducted. Our primary outcome showed an absent effect of tDCS on DCP and AUCg. Additionally, tDCS had an absent effect on CAR, CD, and cortisol concentration variation before-after stimulation. Our pilot study suggests that anodal tDCS showed an absent effect on HPAA activity in individuals with depression. More studies are needed to confirm these findings.

Background This study's main aim was to evaluate the effect of left anodal transcranial direct current stimulation (tDCS) on hypothalamic-pituitary-adrenal axis (HPAA) activity in participants with depression. As an additional exploratory objective, we aimed to find any relationship between baseline morning cortisol concentrations, family history of depression, and somatic symptoms. Materials and Methods A 3-week, randomized, triple-blind, pilot trial was carried out. Participants (n = 47, drop-out: 14.89%) were allocated randomly to one of two groups: tDCS and control group (sham stimulation). Since the effector hormone of the HPAA is cortisol, salivary cortisol was used as an HPAA activity marker. The primary outcome was the effect of tDCS on the diurnal cortisol pattern (DCP). Secondary outcomes were tDCS effects on cortisol awakening response (CAR) and maximal cortisol decline (MCD), as well as the variation of cortisol concentrations between the initiation of tDCS and 2 weeks later. Intention-to-treat and per-protocol analyses were carried out. Results Regarding our primary outcome, we found no significant effectof tDCS on the interaction group * time * daytime. Concerning our secondary outcomes, tDCS had no significant effects on CAR, MCD or cortisol concentration variation between the initiation of tDCS and 2 weeks later in the tDCS group when compared with the sham stimulation group. Finally, an exploratory analysis found a significant relationship between morning cortisol, family history of depression, and somatic symptoms. Conclusions Our main results indicate that anodal tDCS did not affect HPAA activity in depression. More studies are needed to confirm these findings.