Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Trial

Objective: The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, 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. In this study, we assess the utility of raloxifene as an adjunctive treatment for negative symptoms and other psychotic symptoms in postmenopausal women with schizophrenia.

Method: This was a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Barcelona, Spain, and Corporació Sanitària Parc Taulí, Sabadell, Spain. Thirty-three postmenopausal women with schizophrenia (DSM-IV criteria) who exhibited prominent negative symptoms were randomized to either adjunctive raloxifene (16 women; mean age = 60.14 years, SD = 6.41 years) or adjunctive placebo (17 women; mean age = 62.66 years, SD = 4.54 years) for 12 weeks. The period of recruitment lasted from January 2005 through June 2009. Psychopathological symptoms were assessed at baseline and weeks 4, 8, and 12 by means of the Positive and Negative Syndrome Scale.

Results: The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .044), positive (P = .031), and general psychopathological (P = .045) symptoms during the 12-week trial as compared with women receiving placebo.

Conclusions: Raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia who exhibit prominent negative symptoms appears to be useful in improving negative, positive, and general psychopathological symptoms. If more extensive and longer-term studies confirm and expand upon these positive results, the use of raloxifene could be recommended in postmenopausal patients with schizophrenia.

Trial Registration: clinicaltrials.gov Identifier: NCT01041092

J Clin Psychiatry

Submitted: October 1, 2010; accepted November 8, 2010.

Online ahead of print: August 23, 2011 (doi:10.4088/JCP.10m06610).

Corresponding author: Judith Usall, MD, PhD, Parc Sanitari Sant Joan de Déu C/Antoni Pujadas, 42 Sant Boi de Llobregat 08830, Barcelona, Spain (jusall@pssjd.org).

J Clin Psychiatry 2011;72(11):1552-1557

https://doi.org/10.4088/JCP.10m06610