Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder: a double-blind, randomized, placebo-controlled phase 2 trial

TY - JOUR

T1 - Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder

T2 - a double-blind, randomized, placebo-controlled phase 2 trial

AU - Miskowiak, Kamilla Woznica

AU - Ehrenreich, Hannelore

AU - Christensen, Ellen M

AU - Kessing, Lars Vedel

AU - Vinberg, Maj

N1 - © Copyright 2014 Physicians Postgraduate Press, Inc.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Objective: Available drug treatments for bipolar disorder fail to reverse patients' cognitive deficits. Erythropoietin has neurotrophic actions and aids neurocognitive function. The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar disorder. Method: Patients with an ICD-10 diagnosis of bipolar disorder in remission were randomized, with stratification by age and gender, to receive 8 weekly erythropoietin (40,000 IU) or saline (sodium chloride [NaCl], 0.9%) infusions in a doubleblind, parallel-group design. The first patient was randomized in September 2009 and last assessment was completed in October 2012. Patients were assessed at baseline and at weeks 9 and 14. The primary outcome was change in verbal memory indexed by the total words recalled across Rey Auditory Verbal Learning Test learning trials (I-V) from baseline to week 9; secondary outcomes were sustained attention and facial expression recognition; and tertiary outcomes were attention, executive function, subjective cognitive function, and mood. Analysis was by intention to treat, using repeated-measures analysis of covariance adjusted for stratification variables and mood. The statistical threshold for which results were considered significant was P ≤ .05 (2-tailed). Results: 44 patients were randomized; given 1 dropout after baseline, results were analyzed for 43 patients (erythropoietin: n = 23; saline: n = 20). There was no significant improvement of verbal memory in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple reaction times or mood (P values > .16) and were maintained after red blood cell normalization. Conclusions: This is the first trial investigating erythropoietin to treat cognitive dysfunction in bipolar disorder. The findings highlight erythropoietin as a candidate treatment for deficits in attention and executive function in bipolar disorder. Trial Registration: ClinicalTrials.gov

AB - Objective: Available drug treatments for bipolar disorder fail to reverse patients' cognitive deficits. Erythropoietin has neurotrophic actions and aids neurocognitive function. The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar disorder. Method: Patients with an ICD-10 diagnosis of bipolar disorder in remission were randomized, with stratification by age and gender, to receive 8 weekly erythropoietin (40,000 IU) or saline (sodium chloride [NaCl], 0.9%) infusions in a doubleblind, parallel-group design. The first patient was randomized in September 2009 and last assessment was completed in October 2012. Patients were assessed at baseline and at weeks 9 and 14. The primary outcome was change in verbal memory indexed by the total words recalled across Rey Auditory Verbal Learning Test learning trials (I-V) from baseline to week 9; secondary outcomes were sustained attention and facial expression recognition; and tertiary outcomes were attention, executive function, subjective cognitive function, and mood. Analysis was by intention to treat, using repeated-measures analysis of covariance adjusted for stratification variables and mood. The statistical threshold for which results were considered significant was P ≤ .05 (2-tailed). Results: 44 patients were randomized; given 1 dropout after baseline, results were analyzed for 43 patients (erythropoietin: n = 23; saline: n = 20). There was no significant improvement of verbal memory in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple reaction times or mood (P values > .16) and were maintained after red blood cell normalization. Conclusions: This is the first trial investigating erythropoietin to treat cognitive dysfunction in bipolar disorder. The findings highlight erythropoietin as a candidate treatment for deficits in attention and executive function in bipolar disorder. Trial Registration: ClinicalTrials.gov

KW - Adolescent

KW - Adult

KW - Aged

KW - Attention

KW - Bipolar Disorder

KW - Cognition Disorders

KW - Double-Blind Method

KW - Erythropoietin

KW - Executive Function

KW - Female

KW - Humans

KW - Learning

KW - Male

KW - Mental Recall

KW - Middle Aged

KW - Reaction Time

KW - Recognition (Psychology)

KW - Recombinant Proteins

KW - Young Adult

U2 - 10.4088/JCP.13m08839

DO - 10.4088/JCP.13m08839

M3 - Journal article

C2 - 25099079

SN - 0160-6689

VL - 75

SP - 1347

EP - 1355

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

IS - 12

ER -