Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

TY - JOUR

T1 - Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

AU - Miskowiak, Kamilla W

AU - Vinberg, Maj

AU - Harmer, Catherine J

AU - Ehrenreich, Hannelore

AU - Knudsen, Gitte M

AU - Macoveanu, Julian

AU - Hansen, Allan R

AU - Paulson, Olaf B

AU - Siebner, Hartwig R

AU - Kessing, Lars V

PY - 2010/10/13

Y1 - 2010/10/13

N2 - BACKGROUND: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. METHODS/DESIGN: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) 1 in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) 23. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes. TRIAL REGISTRATION: The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.

AB - BACKGROUND: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. METHODS/DESIGN: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) 1 in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) 23. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes. TRIAL REGISTRATION: The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.

KW - Affect

KW - Antidepressive Agents

KW - Attention

KW - Bipolar Disorder

KW - Clinical Protocols

KW - Cognition

KW - Denmark

KW - Depressive Disorder, Major

KW - Double-Blind Method

KW - Erythropoietin

KW - Executive Function

KW - Humans

KW - Memory

KW - Neuronal Plasticity

KW - Neuropsychological Tests

KW - Placebo Effect

KW - Psychiatric Status Rating Scales

KW - Questionnaires

KW - Research Design

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1186/1745-6215-11-97

DO - 10.1186/1745-6215-11-97

M3 - Journal article

C2 - 20942940

SN - 1745-6215

VL - 11

SP - 97

JO - Trials

JF - Trials

ER -