Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy 
in depression: A randomized, double-blind, placebo-controlled trial

Miskowiak, Kamilla W.; Petersen, Jeff Z.; Macoveanu, Julian; Ysbaek-Nielsen, Alexander T.; Lindegaard, Ida A.; Cramer, Katrine; Mogensen, Madel B.; Hammershoj, Lisa G.; Stougaard, Marie E.; Jorgensen, Josefine L.; Schmidt, Lejla Sjanic; Vinberg, Maj; Ehrenreich, Hannelore; Hageman, Ida; Videbech, Poul; Gbyl, Krzysztof; Kellner, Charles H.; Kessing, Lars V.; Jorgensen, Martin B.

doi:10.1016/j.euroneuro.2023.12.004

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Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial

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Ehrenreich, Hannelore
Research Group of Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Citation

Miskowiak, K. W., Petersen, J. Z., Macoveanu, J., Ysbaek-Nielsen, A. T., Lindegaard, I. A., Cramer, K., et al. (2024). Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial. European Neuropsychopharmacology, 79, 38-48. doi:10.1016/j.euroneuro.2023.12.004.

Cite as: https://hdl.handle.net/21.11116/0000-000E-66D6-E

Abstract

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a ‘speed of complex cognitive processing’ composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT.