Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.
OBJECTIVE
There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo.


METHODS
We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels.


RESULTS
We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06).


CONCLUSIONS
Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder.


BACKGROUND
ClinicalTrials.gov identifier: NCT00916552.
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. kamilla@miskowiak.dk.|Copenhagen Psychiatric Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Kamilla Woznica
KW
Miskowiak
Duke Graduate Medical School, Durham, North Carolina, and the National University of Singapore.
A John
AJ
Rush
Department of Biostatistics, University of Copenhagen, Denmark.
Thomas A
TA
Gerds
Copenhagen Psychiatric Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Maj
M
Vinberg
Copenhagen Psychiatric Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Lars V
LV
Kessing
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D019964:Mood Disorders / Q000150:complications*; D017063:Outcome Assessment, Health Care; D055815:Young Adult
D004921:Erythropoietin