Ehrenreich H et al. (2006) Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry [doi:10.1038/sj.mp.4001907]

Growing evidence of the neurodegenerative mechanisms involved in schizophrenia, including progressive loss of cortical gray matter, has extended therapeutic possibilities beyond the currently used antipsychotic drugs. Recombinant human erythropoietin (rhEPO), a drug that exerts neurotrophic and synaptogenic effects, has shown some success in the disorder and could provide the long-term improvement in cognitive function not offered by other drugs. Ehrenreich et al. initiated a proof-of-principle investigation into whether adding rhEPO to existing antipsychotic medication was an effective treatment strategy.

The double-blind, multicenter study focused on 39 chronically ill schizophrenic men with cognitive impairment but no clear signs of ongoing disease possession. On top of their stable antipsychotic regimen, 20 patients were randomized to 3 months of 40,000 IU weekly intravenous rhEPO, and 19 to placebo. Cognitive functions that are severely impaired in patients with chronic schizophrenia (delayed memory, language–semantic fluency, attention and performance on the Wisconsin Card Sorting Test) all improved steadily during the 12-week evaluation period, in both sets of patients. Improvement was greatest in patients on rhEPO, however, with a 16% improvement in cognitive performance over baseline, and a 7% improvement over placebo. rhEPO did not significantly improve psychopathology and social functioning measures or brain volume, but the drug did produce a marked reduction in serum levels of S100B, a marker of glial damage.

The selective and lasting benefit of rhEPO on cognition should, say the authors, encourage new treatment strategies for schizophrenia.