MODEST Trial Finds No Delirium Benefit With tES

Postoperative transcranial electrical stimulation (tES) did not reduce postoperative delirium (POD) in adults aged 65 years or older undergoing elective major surgery, according to results from the double-blind, sham-controlled MODEST randomized clinical trial published in JAMA Network Open.

Investigators randomly assigned 225 patients to α-transcranial alternating current stimulation (tACS), transcranial direct current stimulation (tDCS), or sham stimulation. Earlier in the study, a device malfunction prevented 172 participants from receiving their intended stimulation; those participants were excluded, and additional patients were recruited to complete the planned sample. Among the subsequently randomized cohort, 45 patients dropped out for reasons including canceled surgery and withdrawal of consent, leaving 180 participants in the full analysis set. POD was assessed with the 3-Minute Diagnostic Interview for Confusion Assessment Method.

Ward delirium occurred in 11.5% of the tACS group, 14.3% of the tDCS group, and 9.2% of the sham group. Neither active intervention significantly reduced POD compared with sham. For tACS versus sham, the odds ratio (OR) was 1.60 (95% CI, 0.47-5.46; P=0.45). For tDCS versus sham, the OR was 1.51 (95% CI, 0.49-4.68; P=0.47).

A prespecified exploratory subgroup analysis suggested that tACS might reduce delirium in the postanesthesia care unit among patients undergoing longer operations. The surgery-duration interaction OR was 0.15 (95% CI, 0.02-0.97; P=.046). No adjustment for multiple testing was applied, and the finding requires confirmation. No serious adverse events were reported.

The findings do not demonstrate a uniform preventive benefit from single-session postoperative tES in the studied population. The authors noted that the single-center design, heterogeneous surgical procedures, and lower-than-anticipated delirium incidence may have limited the study’s ability to detect clinically meaningful differences. They called for further research into potentially responsive patient groups, treatment timing, and individualized stimulation parameters.

Source:  Antonenko D, Bublitz V, Leroy S, et al. Transcranial electrical stimulation and delirium among postoperative patients: a randomized clinical trial. JAMA Netw Open. 2026;9(8):e2628284. doi:10.1001/jamanetworkopen.2026.28284