Benefits and harms of atypical antipsychotics for agitation in adults with dementia.
We evaluated the most current evidence regarding the benefits and harms of atypical antipsychotics in adults with dementia. In June 2016, following a protocol developed a priori, we systematically searched several databases for published and unpublished data from randomized controlled trials (RCT), observational studies, and meta-analyses; conducted direct meta-analyses using a random effects model; and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. One high-quality meta-analysis and published and unpublished data from 8 RCTs and 12 large observational studies met inclusion criteria. When compared with placebo, aripiprazole, risperidone, and olanzapine but not quetiapine result in modest (standardized mean difference <0.5 standard deviations) improvement in neuropsychiatric symptoms. Aripiprazole, risperidone, quetiapine, and olanzapine are associated with increased odds of acute myocardial infraction, and risperidone and olanzapine are associated with increased odds of hip fracture. Observational studies suggest no differences in all-cause mortality between atypical antipsychotics. Observational studies suggest that atypical antipsychotics are associated with lower risk of all-cause mortality and extrapyramidal symptoms but higher risk of stroke when compared with conventional antipsychotics. To manage agitation in adults with progressive dementia, clinicians may recommend atypical antipsychotics with continuous monitoring of behavioral symptoms, informing patients and their families or caregivers of the significant risk of adverse effects and baseline risk of acute myocardial infraction and bone fractures.