Effects of Erythropoietin on Depressive Symptoms and Neurocognitive Deficits in Depression and Bipolar Disorder

Lars Vedel Kessing, professor, MD, DMSc.

Status and phase

Completed

Phase 2

Conditions

Mood Disorders

Treatments

Drug: Erythropoietin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00916552

EPO1

Details and patient eligibility

About

Depression and bipolar disorder (mania and depression) may be related to problems with nerve cells not being regenerated as fast as normal and are accompanied by cognitive difficulties including memory, attention and planning problems. There is thus a need for better, more efficient treatments with effects on cognitive function. Erythropoietin (Epo) is involved in brain repair and may be a candidate for future treatment strategies. The investigators have demonstrated that a single dose of Epo improves mood and reduces the processing of negative emotional information in healthy volunteers similar to effects seen with antidepressants. With the current study the investigators aim to build upon this discovery by investigating whether repeated Epo administration has antidepressant effects and is able to reverse cognitive difficulties in patients with depression or bipolar disorder. It is hypothesized that Epo will improve mood in treatment-resistant depression and improve cognitive function in this group and in patients with bipolar disorder in remission. If the study reveals beneficial effects of Epo, this would highlight Epo as a candidate compound for future treatment of depression and bipolar disorder, with the potential to directly promote brain repair mechanisms.

Enrollment

83 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Treatment-resistant depression (defined as failure to respond to at least 2 different types of antidepressants) and an HDRS score of at least 17

Bipolar disorder in remission (HDRS score of max 14 and Young Mania Scale score of max 14) and subjective complaints of moderate to severe cognitive problems on the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) (Fava et al 2006) (score at least 4 on at least 2 domains)
Unchanged antidepressant or mood stabilizing treatment for at least 2 weeks prior to and during the study

Exclusion criteria

Schizophrenia/ schizoaffective disorder
Dependence on or abuse of drugs (including alcohol and benzodiazepines corresponding to more than 22.5 mg Oxazepam daily)
Diabetes
Renal failure
Smoking
Major surgery within 4 weeks prior to inclusion
Previous Epo-treatment
Known allergy or antibodies against Epo
Present or past malignancies
Epilepsy or epilepsy in first degree family Diagnosis (past or present) of a cardiovascular or cerebrovascular disease
Untreated or not sufficiently treated arterial hypertension ("therapy-resistant hypertension")
Initial hematocrit > 50% (males) or > 48% (females)
Initial platelet count above normal range of laboratory
Initial reticulocyte count below norma range of laboratory
Past thromboembolic events or thromboembolic events in first degree family (increased thromboembolic risk)
Contraindications against prophylactic thrombosis treatment
Myeloproliferative disorder, polycythemia
Present immunosuppressive treatment with cyclosporin
Overweight (BMI > 30) or body weight of less than 45 kg or over 95 kg
Acute suicidal risk, present or previous suicide attempts in the past 2 years
Pregnancy or breast feeding
Women who presently use contraceptive pills
Sexually active women with child bearing potential who refuse to use double barrier anticonception methods
Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol
Present illness which in investigator's opinion could affect the patient's participation in the study