Transcranial alternating current stimulation as treatment for delirium: A multicenter randomized double-blind...

Delirium is an acute neuropsychiatric syndrome with currently no effective treatment. The acute encephalopathy underlying delirium is characterized by diffuse oscillatory slowing on electroencephalography (EEG). Based on its capacity to modulate oscillatory activity, 10 Hz transcranial alternating current stimulation (tACS) is a potential hypothesis-driven intervention for delirium. Before investigating potential neurophysiological or clinical effects, it is necessary to establish whether tACS is feasible and safe in delirious patients. This pilot study investigated the feasibility and safety of tACS in 30 hospitalized patients aged ≥50 years with delirium. Participants were randomized double-blind to receive either daily 10 Hz frontal-occipital tACS or sham stimulation for up to 14 days. The first-session completion rate was 94% (active) and 92% (sham). Participants had a median of 3 eligible treatment days (interquartile range [IQR]:2-4). The active group completed a median of 2 tACS sessions (IQR:2-3) and the sham group a median of 3 (IQR:2-4), corresponding to treatment adherence rates of 69% (95% confidence interval [CI]:57-79) and 73% (95% CI:59-83), respectively. The intervention was well-tolerated with no stimulation-related serious adverse events (AEs). AE frequency did not differ between active (35%) and sham (31%) groups. Side effects were mild, transient cutaneous sensations. In conclusion, short-course exposure to 10 Hz tACS can be safely initiated in hospitalized older adults with delirium, with a high first-session completion rate while delivery of repeated daily sessions remained challenging. These findings support further investigation of tACS in delirium, including studies specifically designed to evaluate neurophysiological and clinical effects. Trial Registration: NCT06285721, registered on 2024-02-19.