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

Abstract 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 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 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. Review registration : CRD 42017059946