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

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.


Eligibility Criteria:
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

OR

* 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