Efficacy and tolerability of histamine-2 receptor antagonist adjunction of antipsychotic treatment in schizophrenia: A meta-analysis of randomized placebo-controlled trials

Introduction: No comprehensive meta-analysis has been performed concerning the efficacy and tolerability of adjunctive therapy with histamine-2 receptor antagonists (H₂R-ANTs) in schizophrenia patients who were treated with antipsychotics. Methods: Risk ratios, standardized mean differences (SMD), and 95% confidence intervals were calculated. Results: We included 8 double-blinded, randomized placebo-controlled trials (RCTs) (n=418) that met the inclusion criteria (famotidine: N=3, n=74; nizatidine: N=4, n=292; ranitidine: N=1, n=52). Pooled H₂R-ANTs were not different from placebo with regard to reduction in overall symptoms and body weight. However, pooled H₂R-ANTs resulted in lower body mass index (BMI) than placebo (SMD=-0.68). Moreover, nizatidine was associated with an increase in plasma leptin levels (SMD=-1.14). There were no significant differences in the discontinuation rates due to all-cause, side effects, and inefficacy between pooled H₂R-ANTs and placebo. However, nizatidine produced more depression and dry mouth than placebo. Discussion: H₂R-ANT adjunctive therapy did not improve overall symptoms. To clarify the opposite results between body weight and BMI, future research should investigate long-term efficacy and generate more safety data by using larger samples.