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Treatment modifiers and predictors of risperidone response in dementia: An individual participant data meta-analysis
Hieu T Le1, Edward C Y Lau1, Christine Y Lu1,2,3
1School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Camperdown, Sydney, New South Wales, Australia.
Introduction:
Risperidone is approved for behaviors and psychological symptoms of dementia (BPSD), despite modest efficacy and known risks. Identifying responsive symptoms, treatment modifiers, and predictors is crucial for personalized treatment.
Method:
A one-stage individual participant data meta-analysis of six randomized controlled trials (risperidone: n = 1009; placebo: N = 712) was conducted. Mixed-effects models assessed treatment effects, modifiers, and predictors, with BPSD measured via the Behavioral Pathology in Alzheimer's Disease scale.
Results:
Risperidone showed modest 8 week benefits for aggression (standardized mean difference [SMD]: -0.22; p < 0.001), psychosis (SMD: -0.23; p = 0.001), and anxiety/phobias (SMD: -0.19; p = 0.014), but not for activity, affective, or sleep disturbances. Pharmacokinetic/pharmacodynamic-related factors (e.g., body mass index, endocrine disease, race/ethnicity) potentially modified treatment effects. Week 2 response predicted week 8 improvement (odds ratio: 4.46; p < 0.001).
Discussion:
Risperidone provided symptom-specific benefits in reducing aggression, psychosis, and anxiety/phobias. Week 2 response predicted treatment outcomes, while certain patient characteristics may modify treatment response. Further research is needed to optimize the benefit-risk balance and individualize treatment.
Highlights:
Risperidone modestly reduces symptoms of psychosis, aggression, and anxiety/phobias. Risperidone shows no effect on activity, affective, or sleep disturbances. Patient factors (body mass index, endocrine disease, race/ethnicity) may affect response. Positive response by week 2 predicts significant improvement later.
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