Table 1.

Findings from some notable systematic reviews and meta-analyses comparing risperidone with other atypical antipsychotics or placebo (Schneider et al., 2006; Schneider et al., 2005; Maher et al., 2011; Farlow and Shamliyan, 2017; Jin and Liu, 2019; Yunusa et al., 2019).

Study	Study Type	Study objective	Comparisona	Summary of Findings
				Efficacy	Safetyb
Schneider et al., 2006	SR/MA	Assess the evidence for efficacy and adverse events of atypical antipsychotics for people with dementia.	Risperidone vs Placebo	Behave-AD; risperidone significantly improved Behave-AD compared with placebo (WMD, −1.48; 95% CI, −2.35, −0.61; 4 studies). CMAI; risperidone significantly improved CMAI compared with placebo (WMD, −3.00; 95% CI, −4.22, −1.78; 3 studies) BPRS; risperidone did not significantly improve BPRS compared with placebo (WMD, 0.60; 95% CI, −1.82, 3.02; 1 study). NPI; risperidone did not significantly improve NPI compared with placebo (WMD, 2.60; 95% CI, −2.70, 7.90; 1 study). CGI-S; risperidone did not significantly improve CGI-S compared with placebo (WMD, −0.09; 95% CI, −0.21, 0.02; 3 studies).	CVAE; There was a significant increase in the risk of CVAE for risperidone compared with placebo (OR, 3.43; 95% CI, 1.60, 7.32; 4 studies). Death; There was no significant increase in the risk of death for risperidone compared with placebo (OR, NR; 95% CI, NR; 5 studies).
Schneider et al., 2005	SR/MA	Assess the evidence for increased mortality from atypical antipsychotics for people with dementia.	Risperidone vs Placebo	N/A	CVAE; N/A Death; There was no significant increase in the risk of death for risperidone compared with placebo (OR, 1.30; 95% CI, 0.76, 2.23; 5 studies).
Maher et al., 2011	SR/MA	Assess the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration.	Risperidone vs Placebo	Global scorec; risperidone did not significantly improve global scores compared with placebo (SMD, 0.19; 95% CI, 0, 0.38; 6 studies).	CVAE; There was a significant increase in the risk of CVAE for risperidone compared with placebo (OR, 3.12; 95% CI, 1.32, 8.21; 4 studies). Death; NR
Farlow and Shamliyan, 2017	SR/MA	Assess the efficacy and safety of atypical antipsychotics for people with dementia.	Risperidone vs Placebo	Behave-AD; risperidone did not significantly improve Behave-AD compared with placebo (SMD, −0.20; 95% CI, −0.40, 0.00; 4 studies). BPRS; risperidone did not significantly improve BPRS compared with placebo (SMD, −0.10; 95% CI, −0.60, 0.30; 2 studies). NPI; risperidone did not significantly improve NPI compared with placebo (SMD, −0.10; 95% CI, −0.60, 0.40; 2 studies). CGI; risperidone significantly improved CGI-T compared with placebo (SMD, −0.40; 95% CI, −0.70, −0.10; 4 studies).	CVAE; There was a significant increase in the risk of CVAE for risperidone compared with placebo (OR, 4.53; 95% CI, 1.75, 11.72; 4 studies). Death; There was no significant increase in the risk of death for risperidone compared with placebo (RR, 3.70; 95% CI, 0.20, 88.5; 1 study).
Yunusa et al., 2019	SR/NMA	Assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis.	Risperidone vs Placebo vs Aripiprazole vs Olanzapine vs Quetiapine	CMAI; There was no statistically significant difference between risperidone and other atypical antipsychotics based on CMAI. Risperidone significantly improved CMAI compared with placebo (SMD, −0.30; 95%CI, −0.55, −0.05) BPRS; There was no statistically significant difference between risperidone and other atypical antipsychotics based on BPRS. Risperidone did not significantly improved BPRS compared with placebo (SMD, −0.10; 95% CI, −0.29, 0.09). NPI; There was no statistically significant difference between risperidone and other atypical antipsychotics based on NPI. Risperidone did not significantly improved NPI compared with placebo (SMD, −0.01; 95% CI, −0.19, 0.18).	CVAE; There was no statistically significant difference between risperidone and other atypical antipsychotics based on CVAE.There was a significant increase in the risk of CVAE for risperidone compared with placebo (OR, 3.85; 95% CI, 1.55, 9.55). Death; There was no statistically significant difference between risperidone and other atypical antipsychotics based on mortality. No significant increase in the risk of death for risperidone compared with placebo (RR, 1.32; 95% CI, 0.77, 2.27).
Jin and Liu, 2019	SR/NMA	Assess the comparative efficacy and safety of pharmacological and nonpharmacological therapies for the BPSD.	Risperidone vs Placebo vs Aripiprazole vs Olanzapine vs Quetiapine vs Haloperidol vs Other antipsychotic agents	CMAI; There was no statistically significant difference between risperidone and other atypical antipsychotics based on CMAI. Risperidone significantly improved CMAI compared with placebo (MD, −2.58; 95% CrI, −5.20, −0.60) NPI; There was no statistically significant difference between risperidone and other atypical antipsychotics based on NPI. Risperidone did not significantly improved NPI compared with placebo (MD, −3.20; 95% CrI, −6.08, −0.31).	CVAE; There was no statistically significant difference between risperidone and other atypical antipsychotics based on CVAE. There was a significant increase in the risk of CVAE for risperidone compared with placebo (OR, 3.94; 95% CrI, 1.85, 10.73). Death; NR

BPDS, behavioral and psychological symptoms of dementia; BPRS, Brief Psychiatry Rating Scale; CGI, Clinical Global Impression (total score); CGI-S, Clinical Global Impression – Severity scale; CMAI, Cohen-Mansfield Agitation Inventory; CVAE, cerebrovascular adverse events; CI, confidence interval; CrI, credible interval; MD, mean difference; N/A, not applicable or not available; NMA, network meta-analysis; NR, not reported; NPI, neuropsychiatry inventory; OR, odds ratio; RR, relative risk; SR/MA, systematic review and meta-analysis (pairwise); SR/NMA, systematic review and network meta-analysis; SMD, standardized mean difference; WMD, weighted mean difference.

^aRefers to only comparisons involving risperidone.

^bSafety outcomes limited to death and cerebrovascular adverse events for which there are regulatory warnings across the world.

^cRefers to a total global score that included cumulative psychiatric symptoms of delusions, hallucinations, suspiciousness, dysphoria, anxiety, motor agitation, aggression, hostility, euphoria, disinhibition, irritability, apathy, and other behavioral disturbances.