Optimized Multichannel tDCS Beats Conventional Protocol in MDD

An optimized multichannel transcranial direct current stimulation (tDCS) protocol delivering 4 mA (precisely 3.99 mA) total injected current produced significantly greater and faster reductions in depressive symptoms than conventional 2 mA tDCS or sham stimulation in a randomized, sham-controlled trial of patients with major depressive disorder (MDD).¹

Prior home-based conventional tDCS trials have shown efficacy without the precision of individualized targeting.² Fully personalized, MRI-based tDCS protocols improve targeting but remain resource-intensive and difficult to scale in routine care. The multichannel montage tested in this trial used computational modeling on a template head model rather than patient-specific imaging, pairing improved targeting with clinical feasibility.¹

"Both interventions showed clinical improvement, but the multichannel intervention showed earlier and stronger effect, which means the depression symptom was relieved earlier," said Mohammad Ali Salehinejad, PhD, from the department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at RWTH Aachen University, in an interview with HCPLive.

Multichannel tDCS Efficacy in Major Depressive Disorder

The trial randomized 71 adults with unipolar, nonpsychotic MDD who failed ≥ 1 antidepressant to have optimized multichannel tDCS (4 mA via 7 small electrodes), conventional tDCS (2 mA via 2 sponge electrodes), or sham stimulation. Sixty patients provided endpoint data (n = 20 per arm), and all participants received 30 daily sessions over 6 weeks.

Depressive symptoms were assessed via the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) at baseline, sessions 10, 20, and 30, and at 1- and 3-month follow-up. Multichannel tDCS reduced MADRS scores by a mean of 21.50 points (95% CI, 17.77-25.22) by week 6, compared with 13.50 points (95% CI, 10.44-16.55) for conventional tDCS and 6.30 points (95% CI, 3.42-9.17) for sham (group×time interaction, P <.001).

Treatment response, defined as a ≥ 50% reduction in MADRS score, occurred in 75% (15/20) of the multichannel group compared with 45% (9/20) for conventional tDCS and 20% (4/20) for sham, yielding a number needed to treat of 2 (95% CI, 1-3) for multichannel tDCS versus sham. Symptom reduction with multichannel tDCS emerged as early as session 10, while conventional tDCS did not separate from sham until sessions 20 to 30.

Multichannel tDCS Safety, Blinding, and Cognitive Effects

Beck Depression Inventory-II scores followed a similar pattern, decreasing significantly from session 10 in the multichannel group and from session 30 in the conventional group, with no significant change in sham. Multichannel tDCS also improved working memory, sustained attention, and executive function on CANTAB testing, effects not observed with conventional tDCS, and increased frontotemporal and prefrontal-central functional connectivity on EEG.

No serious adverse events occurred in any arm. The multichannel group reported more adverse effects per participant (5.05 ± 0.94) than conventional (2.50 ± 1.15) or sham (2.85 ± 1.04) tDCS, driven mainly by itching, tingling, burning, skin redness, and headache tied to the higher current density at the 7-electrode sites.

Blinding was unsuccessful in the multichannel arm, with 19 of 20 participants correctly identifying active stimulation, while the conventional arm showed chance-level guessing. Guessed treatment intensity was not correlated with symptom improvement within the multichannel arm (P =.913).

"One possible solution to resolve this issue is to use [a] cream which makes the skin numb,” Salehinejad said. “We sometimes use this so that the people do not understand that they are receiving any stimulation.”

References

1. Salehinejad MA, Abdi M, Dadashi M, et al. Optimized multichannel 4 mA vs conventional transcranial direct current stimulation for major depressive disorder: A randomized sham-controlled trial. Mol Psychiatry. 2026;31(8):4632-4644. doi:10.1038/s41380-026-03560-0

2. Woodham RD, Selvaraj S, Lajmi N, Hobday H, Sheehan G, Ghazi-Noori AR, Lagerberg PJ, Rizvi M, Kwon SS, Orhii P, Maislin D, Hernandez L, Machado-Vieira R, Soares JC, Young AH, Fu CHY. Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial. Nat Med. 2025 Jan;31(1):87-95. doi: 10.1038/s41591-024-03305-y. Epub 2024 Oct 21. PMID: 39433921; PMCID: PMC11750699.