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.

People with schizophrenia have substantially poorer physical health than the general population1-4, which is often attributed to an interaction between social circumstances, lifestyle factors and treatment effects5. For instance, behavioral research has demonstrated that people with schizophrenia are less physically active and exhibit more sedentary behavior than the general population6, have a higher quantity but lower quality of dietary food intake7, and increased adverse health behaviors, such as smoking8. Additionally, psychiatric treatment with antipsychotics and other commonly prescribed agents, such as mood stabilizers and antidepressants, further increases the risk of physical health conditions9, 10. Consequently, people with schizophrenia more frequently have cardio‐metabolic diseases11-13, respiratory diseases14, chronic pain15, fractures16, and lower physical fitness17, 18 than the general population.

This increased somatic risk is associated with a lower physical health related quality of life19, 20, but, despite this increased risk, access to monitoring, physical health care and intervention for those with schizophrenia are suboptimal compared to the general population21, 22. Resultantly, people with schizophrenia experience a 10‐20 year gap in life expectancy, primarily driven by this poorer physical health13, 23. Furthermore, the physical health inequalities experienced by people with schizophrenia have been observed across the globe24 and have not improved over time25.

Given this gross inequality, there has been a substantial increase in efforts to improve the physical health of this at‐risk population5, 26. To address the physical health disparity, a number of individual meta‐analyses have led to national and international evidence‐based recommendations for or against specific pharmacological and non‐pharmacological intervention options27-34.

Despite this rapid expansion of meta‐analytic evidence on interventions for tackling poor physical health in people with schizophrenia, no summary of this top‐tier of evidence exists, nor is there a direct quantitative comparison of the evidence between all individual and/or combined pharmacological and non‐pharmacological strategies. Moreover, the quality of these meta‐analyses and the included trials has not been comprehen‐sively evaluated, which is an indispensable step before more rigorous treatment recommendations can confidently be made.

In order to address this gap within the literature, we set out to aggregate the existing top‐tier evidence from the most recent/largest published meta‐analyses of randomized trials of physical health interventions, in order to determine the comparative quality of evidence and magnitude of efficacy for pharmacological and non‐pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders.