The findings of a meta-analysis published in Schizophrenia Research indicated that raloxifene, commonly used to aid the prevention of osteoporosis, was effective as an adjunctive treatment in postmenopausal patients with schizophrenia.

The lowered estrogen levels experienced during and after menopause have been associated with worse psychotic symptoms in women with schizophrenia. However, long-term estrogen augmentation can pose serious health risks to breast and uterine tissue. The advantage of selective estrogen receptor modulators, including raloxifene, is that they do not stimulate those tissues.

The investigators identified 5 double-blind, randomized controlled trials across several Chinese and English language databases that compared adjunctive raloxifene with placebo. The trials comprised 240 patients with a mean age of 58.2 years and an average onset age of illness of 28.3 years.

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Each trial lasted between 8 and 24 weeks, with 125 patients in raloxifene groups (60 mg/d or 120 mg/d) and 115 in placebo groups. The primary outcome measure was total psychopathology as graded by the Positive and Negative Syndrome Scale, with individual positive and negative symptom severity as secondary outcomes.

The results of several previous raloxifene trials from 2010 onward have been inconsistent. However, the meta-analysis showed raloxifene to be effective for positive symptoms, negative symptoms, and general psychopathology, with greatly homogeneous results.

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Although the trials themselves were all graded as high quality by the Jadad scale (mean 4.6, with scores <3 considered low quality), the investigators encouraged caution when interpreting results because of the small sample size of each trial and the limited number of trials available for analysis. They also noted that other studies have suggested that the efficacy of raloxifene may not generalize to other patient groups, including men or young to middle-aged patients with schizophrenia.


Zhu XM, Zheng W, Li X-H, et al. Adjunctive raloxifene for postmenopausal women with schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials [published online February 5, 2018]. Schizophr Res. doi:10.1016/j.schres.2018.01.017