Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial

Eur Neuropsychopharmacol. 2014 Feb;24(2):223-31. doi: 10.1016/j.euroneuro.2013.11.012. Epub 2013 Dec 1.


Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60 mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms.

Trial registration: ClinicalTrials.gov NCT01041092.

Keywords: Cognitive function; Postmenopausal women; Raloxifene; Schizophrenia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / therapeutic use
  • Attention / drug effects*
  • Double-Blind Method
  • Executive Function / drug effects*
  • Female
  • Humans
  • Memory / drug effects*
  • Middle Aged
  • Neuropsychological Tests
  • Postmenopause
  • Raloxifene Hydrochloride / therapeutic use*
  • Schizophrenia / drug therapy*
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Socioeconomic Factors
  • Time Factors
  • Treatment Outcome


  • Antipsychotic Agents
  • Selective Estrogen Receptor Modulators
  • Raloxifene Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT01041092