Efficacy and safety of intravenously applied caffeine augmentation in electroconvulsive therapy

Electroconvulsive therapy (ECT) is a neuromodulation procedure that uses short electrical pulses causing a brief generalized seizure to treat depression, mania, schizophrenia, and catatonia. Achieving sufficient seizure length is crucial for maintaining therapeutic efficacy, as it influences treatment response. However, over successive sessions, seizure length becomes shorter requiring an increased energy set to generate a sufficient seizure, potentially causing more side effects. Caffeine augmentation offers a promising tool by enhancing neuronal excitability via adenosine receptor modulation. This retrospective study assessed the effects of intravenous caffeine citrate (200 mg) on seizure quality during ECT. Data from 276 ECT sessions across 69 patients at the University Psychiatric Clinics Basel were analyzed. We examined seizure indicators-EEG seizure length, peak heart rate, and energy set- by comparing the last two ECT sessions before caffeine administration with the first two sessions after, controlling for anesthetic effects and their interactions. Caffeine augmentation significantly increased EEG seizure length (t (67) = 8.20, p < 0.001, d = 1.23) and significantly reduced the required energy (t (67) = 4.42, p < 0.001, d = 0.65). There was no significant change in peak heart rate (t (45) = 1.66, p = 0.17, d = 0.17) or other seizure quality metrics or side effects. Type of anesthesia did not affect outcomes, except for energy set where we observed a significant interaction-etomidate combined with caffeine resulted in a smaller energy increase compared to propofol (F (198) = 0.04, η ²  = 0.04). Our findings suggest that intravenous caffeine augmentation safely enhances seizure length and slows energy set increases in ECT without affecting cardiovascular markers, supporting its use as an effective augmentation strategy to improve ECT efficacy.