Abstract
BackgroundDepression 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/designThe 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) [2,3]. 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 registrationThe 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.
Highlights
Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function
Symptoms and quality of life are measured at baseline and weeks 5, 9 and 14 using a variety of rating scales including the Hamilton Depression Rating Scale 17 items (HDRS-17) [1], Young Mania Rating Scale (YMRS) [40], Beck Depression Inventory (BDI) [41], Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) [42], and the EuroQol visual analogue scale (VAS) for quality of life (EQ-5D) [43]
The present EPO study is the first clinical trial investigating whether repeated administration of Epo is able to improve mood and reverse neurocognitive dysfunction in patients with treatment resistant depression or bipolar illness in remission
Summary
Depression and bipolar disorder are associated with neurodegenerative processes, reduced neuroplasticity and neuropsychological dysfunction, which often persist even after clinical remission. Serotonergic and noradrenergic antidepressants increase the neural and cognitive processing of positive emotional information and down-regulate the processing of negative threat-relevant information after acute and 7 days administration and in the absence of changes in mood in healthy volunteers [28,29] and in depressed patients [30]. Such actions contrast with heightened recognition and neural responses to threatening information in depression [31,32] and may be an important mechanism of antidepressant drug treatment. Together with its known effects on neuroplasticity in animal models, these findings highlight Epo as a new candidate treatment for affective disorders
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