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Trials. 2018 Apr 19;19(1):234. doi: 10.1186/s13063-018-2627-2.

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial.

Author information

1
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
2
Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
3
Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark.
4
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
6
Department of Neuroanaesthesia, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
7
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk.
8
Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk.
9
Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. kamilla.miskowiak@regionh.dk.

Abstract

BACKGROUND:

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity.

METHODS/DESIGN:

The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library.

DISCUSSION:

If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

KEYWORDS:

Bipolar disorder; Cognition; Cognitive side effects; Depression; Electroconvulsive therapy; Erythropoietin; Functional magnetic resonance imaging; Unipolar disorder

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