CATATOnia treatment with transcranial direct current ElectroStimulation: protocol of a randomised, double-blind, placebo-controlled bicentric superiority study (CATATOES)

Background Catatonia is a severe psychomotor syndrome with high morbidity and mortality. Lorazepam and electroconvulsive therapy (ECT) are the main recommended treatments. Lorazepam-resistant catatonia accounts for about 30% of cases, particularly in neurodevelopmental disorders. ECT is crucial in these situations but faces challenges of tolerability and accessibility. Transcranial direct current stimulation (tDCS), a promising intervention, is emerging as a non-invasive, cost-effective neurostimulation tool and has demonstrated efficacy and safety in case reports and small series of catatonic patients (N < 10). The CATATOES study aims to assess the efficacy and safety of tDCS using a randomised, double-blind, placebo-controlled, bicentric superiority trial involving 70 patients with catatonia. Secondary objectives aim to highlight the mechanism of action of tDCS and to explore the pathophysiology of catatonia. Methods Seventy participants with lorazepam-resistant catatonia will undergo 20 sessions of active or sham tDCS, administered twice daily at two mA for 20 minutes, with anodal stimulation in the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation in the left temporoparietal junction (TPJ). In addition to daily clinical assessment, patients will undergo (i) structural, functional and diffusion magnetic resonance imaging (MRI), (ii) 64-channel resting state electroencephalogram (EEG), and (iii) blood test with inflammatory, neurogenesis and genetic markers, before, during and after the treatment course. Discussion Catatonia is in critical need of therapeutic improvement. We anticipate that this study will pave the way for the routine use of tDCS in the treatment of lorazepam-resistant catatonia, ultimately contributing to a reduction of morbidity, mortality, and associated costs of catatonia. ClinicalTrials.gov Identifier NCT06139432; Registration date 11/24/2023