Adjunctive raloxifene for postmenopausal women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials

Objective: Raloxifene, a selective estrogen receptor modulator, has been used in treating postmenopausal women with schizophrenia with inconsistent results. This meta-analysis of randomized, double-blind, placebo-controlled trials (RCTs) examined its efficacy and safety for postmenopausal women with schizophrenia. Method: Standardized mean differences (SMDs) and risk ratio (RR) together with their 95% confidence intervals (CIs) were calculated using the random effects model. Results: The meta-analysis included 5 RCTs (n-240) comparing raloxifene (n-125, 60 or 120 mg/day) with placebo (n= 115). Adjunctive raloxifene outperformed placebo with regard to the Positive and Negative Syndrome Scale (PANSS) total psychopathology [n= 240, SMD:-0.64 (95% CI:-0.90, -0.37), P < 0.00001; I-2= 0%], positive symptoms [n= 240, SMD:-0.49 (95% CI:-0.81, -0.16), P= 0.003; I-2= 29%], negative symptoms [n= 240, SMD:-0.43 (95% CI:-0.68, -0.17), P = 0.001; I-2 = 0%], and general psychopathology scores [n = 240, SMD:-0.66 (95% CI:-0.92,-0.39), P b 0.00001; I-2= 0%]. Both groups had similar rates of adverse events and discontinuation (n= 159, RR: 1.32 (95% CI: 0.65, 2.70), P= 0.44, I-2= 0%). Conclusion: Adjunctive raloxifene appears to be effective and safe in improving psychotic symptoms for postmenopausal women with schizophrenia.