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Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression

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Authors:
  • Miskowiak, Kamilla W ;
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    Orcid logo0000-0003-2572-1384
    Section of Occupational and Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet
  • Vinberg, Maj ;
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    Orcid logo0000-0002-5982-1335
    Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Christensen, Ellen M ;
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    unknown
  • Bukh, Jens Otto Drachmann ;
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    unknown
  • Harmer, Catherine J ;
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    unknown
  • Ehrenreich, Hannelore ;
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    unknown
  • Kessing, Lars V
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    Orcid logo0000-0001-9377-9436
    Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Subtitle:
A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial
DOI:
10.1038/npp.2013.335
Abstract:
Pharmacological treatments for depression have insufficient efficacy in 30-40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel-group design. Patients were assessed at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17 score. Global assessment of function (GAF) was reported in addition. Secondary outcome was remission rate, and tertiary outcomes were changes in Rey Auditory Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were depression and cognition composite scores. HDRS-17, GAF, and remission rates showed no effects of EPO over saline at week 9 (P-value ≥ 0.09). However, EPO improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow-up week 14 (P-values ≤ 0.04). EPO enhanced verbal recall (P=0.02) and recognition (P=0.03), which was sustained at follow-up (P-values ≤ 0.04). Exploratory analysis in patients fulfilling depression severity criteria at trial start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which was sustained at week 14 (P-values ≤ 0.05). Exploratory analysis in the complete cohort showed that EPO reduced depression composite at weeks 9 and 14 (P-values=0.02). The findings of this exploratory study highlight EPO as an interesting compound for treatment-resistant depression, which deserves further investigation.
Type:
Journal article
Language:
English
Published in:
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 2014, Vol 39, Issue 6, p. 1399-1408
Keywords:
Adult; Affect; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Double-Blind Method; Erythropoietin; Female; Follow-Up Studies; Humans; Male; Memory; Middle Aged; Psychiatric Status Rating Scales; Recombinant Proteins; Remission Induction; Time Factors; Treatment Outcome; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2014
Scientific Level:
Scientific
ID:
256386781

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