TY - JOUR

T1 - Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression

T2 - A randomized, double-blind, placebo-controlled trial: Effects of EPO on cognitive side-effects of ECT

AU - Miskowiak, Kamilla W.

AU - Petersen, Jeff Z.

AU - Macoveanu, Julian

AU - Ysbæk-Nielsen, Alexander T.

AU - Lindegaard, Ida A.

AU - Cramer, Katrine

AU - Mogensen, Madel B.

AU - Hammershøj, Lisa G.

AU - Stougaard, Marie E.

AU - Jørgensen, Josefine L.

AU - Schmidt, Lejla Sjanic

AU - Vinberg, Maj

AU - Ehrenreich, Hannelore

AU - Hageman, Ida

AU - Videbech, Poul

AU - Gbyl, Krzysztof

AU - Kellner, Charles H.

AU - Kessing, Lars V.

AU - Jørgensen, Martin B.

N1 - Publisher Copyright: © 2023

PY - 2024

Y1 - 2024

N2 - 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. Trial registrations: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

AB - 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. Trial registrations: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

KW - Cognition

KW - ECT

KW - Erythropoietin

KW - Randomized controlled trial

KW - Treatment

U2 - 10.1016/j.euroneuro.2023.12.004

DO - 10.1016/j.euroneuro.2023.12.004

M3 - Journal article

C2 - 38128460

AN - SCOPUS:85180585805

VL - 79

SP - 38

EP - 48

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -