The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials.

We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta-analyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=-0.98) and exercise interventions (SMD=-0.96), followed by psychoeducation (SMD=-0.77), aripiprazole augmentation (SMD=-0.73), topiramate (SMD=-0.72), d-fenfluramine (SMD=-0.54) and metformin (SMD=-0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=-1.10) and topiramate (SMD=-0.69) demonstrated the best evidence, followed by dietary interventions (SMD=-0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=-0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=-0.71) and metformin (SMD=-0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=-0.39), dietary interventions (SMD=-0.37) and aripiprazole augmentation (SMD=-0.34), whereas insulin resistance improved the most with metformin (SMD=-0.75) and rosiglitazone (SMD=-0.44). Topiramate had the greatest efficacy for triglycerides (SMD=-0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=-0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=-0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=-0.35 to -0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.