Key Takeaways
Extended Takeaways
- The prespecified intent-to-treat primary end point was narrowly missed at 2 weeks despite improvement in both groups: BDI-II change was 16.65 with active treatment and 14.36 with sham, for a between-group difference of 2.04 (1-sided P = .056, 95% CI, −0.476 to 4.549).
- Adherence appears clinically important for home-based tACS: among participants with 100% compliance in the first 14 days, active treatment showed greater BDI-II improvement than sham at 2 weeks (difference: 3.72, P = .005, 95% CI, 1.103 to 6.340), with significant effects also seen at 1 week (difference: 3.10, P = .022) and 4 weeks (difference: 4.10, P = .018).
- A signal for sex-specific benefit emerged, with females showing greater improvement at week 2 in both intent-to-treat analysis (17.9 vs 14.2, respectively; nominal subgroup P=.020) and per-protocol analysis (18.3 vs 13.76; nominal subgroup P=.008), while no nominally significant difference was seen in males.
- By week 4, active tACS was associated with a higher BDI-II responder rate than sham, reaching 65.08% vs 52.71% (P = .045), suggesting that symptomatic separation may become more evident over several weeks even when early between-group differences are modest.
- The safety profile was favorable in this remote trial: 19 subjects (15.1%) in the active group reported 34 events and 10 subjects (7.8%) in the control group reported 13 events, with no serious AEs and only 1 AE (skin discomfort) leading to device discontinuation.
- This protocol tested a pragmatic at-home regimen of 20 minutes twice daily using a 2 mA (±10% tolerance) device, and concurrent antidepressant use did not appear to alter the week 2 outcome within the active group (P = .543).
