Further improving the cognitive effect profile of electroconvulsive therapy (ECT): The case for studying carbamylated erythropoietin

Kellner, Charles H.; Adams, DM; Benferhat, A.

doi:10.1016/j.mehy.2015.01.007

Cited by 14 publications

(6 citation statements)

References 54 publications

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“…carbamylation of EPO [451,452]. This strategy takes advantage of differences between the brain-specific and hematopoietic EPO receptors [452][453][454]. Interestingly, the beneficial effects of EPO on cognition might also extend to cognitive deficits induced by electroconvulsive therapy (ECT).…”

Section: Erythropoietinmentioning

confidence: 99%

Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

Bittner¹,

Barnes-Scheufler²,

Hettwer³

et al. 2021

Preprint

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Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

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Section: Erythropoietinmentioning

confidence: 99%

Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

Bittner¹,

Barnes-Scheufler²,

Hettwer³

et al. 2021

Preprint

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“…With the development of studying, recently, CEPO has been extended to other areas about the protective effects in addition to nervous system, kidney and heart as discussed above. In these studies, CEPO was supposed to be highly effective of wound healing (37), improving breathing during hypoxia (38), and attenuating cognitive effects of electroconvulsive therapy (39).…”

Section: Cepo-mediated Protection In Other Organs and Tissuesmentioning

confidence: 99%

Carbamylated Erythropoietin and Its Role of Tissue Protection

Li¹,

Diao²,

Ma³

et al. 2017

J Anesth Perioper Med

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Aim of review:We reviewed the study of carbamylated erythropoietin (CEPO) and its probable mechanism involved in the regulation of tissue-protection. Methods: Recent published literatures in this area were inclusive and reviewed. Recent findings: CEPO has equivalent tissue-protective properties as recombinant human erythropoietin (rhEPO) but with non-erythropoietic effects. It shows protective properties on nervous system, heart, kidney and some other organs, which are associated with inhibition of apoptosis, restoration of vascular autoregulation and attenuation of inflammatory responses. However, the underlying mechanism of CEPO responsible for its beneficial effects is still not well-known. Summary: CEPO gradually turned into a promising drug candidate at least for many diseases caused by ischemia reperfusion injury. The safety and efficacy of CEPO in clinical are warranted in the future.

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“…Therefore, novel treatments that counteract these side effects have the potential to improve current treatment strategies by allowing a greater number of severely ill patients to get earlier and more effective treatment with fewer cognitive side effects. However, research efforts into identification of methods to attenuate the cognitive side effects of ECT treatment without hampering its clinical efficacy have thus far been unsuccessful [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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

Schmidt

Petersen

Vinberg

et al. 2018

Trials

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BackgroundElectroconvulsive 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/designThe 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.DiscussionIf 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 registrationClinicalTrials.gov, NCT03339596. Registered on 10 November 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2627-2) contains supplementary material, which is available to authorized users.

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Further improving the cognitive effect profile of electroconvulsive therapy (ECT): The case for studying carbamylated erythropoietin

Cited by 14 publications

References 54 publications

Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

Carbamylated Erythropoietin and Its Role of Tissue Protection

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

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