Transcranial alternating current stimulation for major depressive disorder: An updated systematic review and meta-analysis of randomized trials with GRADE assessment
In brief
Transcranial stimulation more than doubled depression response odds, but symptom scores showed no clear benefit
Across nine randomized trials, transcranial alternating current stimulation was linked to more than twice the odds of treatment response and nearly five times the odds of remission. It did not significantly lower average symptom scores, and participants were more likely to report at least one adverse event. Heterogeneous protocols and low-to-moderate evidence certainty mean routine use is not supported.
- Journal
- Journal of affective disorders (Q1)
- Published
- 15 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Yehia Nabil, Khaled Abdalla Moghib, Zeyad Tarek, Zeinab Helmy, Nourhan Hatem, Abd El-Hai Ahmed Mansour, et al.
- PMID
- 42880603
- DOI
- 10.1016/j.jad.2026.122606
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (paper of the day, 16 October 2026): tACS for major depressive disorder, systematic review
Abstract
PURPOSE: Transcranial alternating current stimulation (tACS) may modulate neural oscillations implicated in major depressive disorder (MDD). This systematic review and meta-analysis assessed the efficacy, follow-up effects, tolerability, and safety of tACS in adults with MDD. METHODS: PubMed/MEDLINE, CENTRAL, Scopus, Web of Science Core Collection, and Embase were searched from inception to March 29, 2026, for randomized controlled trials of active tACS in adults with MDD. Primary analyses compared active tACS with sham or inactive control, while active-protocol comparisons were analyzed separately. Random-effects models were used to calculate pooled mean differences (MDs) or odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2, and certainty of evidence was evaluated using the GRADE approach. RESULTS: Eleven reports from nine randomized trials were included. Active tACS did not significantly reduce clinician-rated depressive symptom severity compared with control (8 studies, 471 participants; MD -1.80, 95% CI -4.80 to 1.20; I2 = 89.8%), indicating substantial heterogeneity. However, tACS was associated with higher odds of treatment response (8 studies, 680 participants; OR 2.41, 95% CI 1.28-4.56; I2 = 62.1%) and remission (4 studies, 270 participants; OR 4.69, 95% CI 2.37-9.28; I2 = 30.1%). A significant effect was also observed for response at the latest reported assessment (7 studies, 608 participants; OR 2.70, 95% CI 1.62-4.49; I2 = 20.3%). Regarding safety, active tACS increased the likelihood of at least one adverse event (3 studies, 475 participants; OR 1.95, 95% CI 1.12-3.41), while estimates for headache and cutaneous symptoms were imprecise and not significantly different between groups. Overall certainty of evidence ranged from very low to moderate. CONCLUSION: tACS may improve response and remission rates in MDD, but its effect on mean symptom severity remains uncertain. High heterogeneity and limited data for protocol-specific subgroup analyses reduce interpretability, as pooled estimates reflect heterogeneous stimulation parameters rather than specific regimens. Given the small evidence base and limited certainty, routine clinical use cannot be recommended. Well-powered, standardized, and independently conducted trials with longer follow-up are required.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.