Review of: Weiser M et al, J Clin Psychiatry 2017;78:e758–e765

Since estrogen can affect neurotransmitter functioning, there has been some interest in using estrogen modulators to treat psychiatric conditions, including schizophrenia. Raloxifene is a selective estrogen receptor modulator (SERM) with some preliminary evidence for effectiveness in women with schizophrenia.

In this double-blind, multi-center study, 200 postmenopausal schizophrenic/schizoaffective women were treated for 16 weeks with either raloxifene or placebo augmentation of their antipsychotic drug treatment regimen. The study was conducted at 38 sites in Romania and Moldova, suggesting an average of 5 patients per site. The results were unequivocally negative. Indeed, subjects in the raloxifene treatment group fared significantly worse on the Positive and Negative Syndrome Scale (PANSS) than did the placebo group, an unexpected outcome the authors attribute to chance. There were no significant differences between groups in Clinical Global Impression—Severity or Composite Brief Assessment of Cognition in Schizophrenia scores.

TCPR’s Take
As the authors indicate, their data “does not support the use of raloxifene in severely decompensated schizophrenia patients.” These results are clear, but they may not be definitive. Given the many research sites, the potential for inter-site variability (in diagnosis, conduct of the study, assessments, etc) was quite large. In addition, the postmenopausal schizophrenic women had been ill for an average of over 20 years and had an average of about 20 hospitalizations, suggesting they were refractory to conventional treatments. There is a need for additional studies, with more subjects per site, less-ill women, and perhaps different SERMs.