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Background Prescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia. Methods We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies. Results Our systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47). Conclusion Although antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms. PROSPERO registration CRD42017050130.

Osteoporosis is affecting over 200 million people worldwide. Despite available guidelines, care for these patients remains sub-optimal. We developed an osteoporosis tool to address the multiple dimensions of chronic disease management. Findings from its evaluation showed a significant increase from baseline in osteoporosis investigations and treatment, so we are revising this tool to include multiple chronic conditions including an update of evidence about osteoporosis. Our objectives were to conduct a systematic review of osteoporosis interventions in adults at risk for osteoporosis. We searched bibliometric databases for randomized controlled trials (RCTs) in any language evaluating osteoporosis disease management interventions in adults at risk for osteoporosis. Reviewer pairs independently screened citations and full-text articles, extracted data, and assessed risk of bias. Analysis included random effects meta-analysis. Primary outcomes were osteoporosis investigations and treatment, and fragility fractures. Fifty-five RCTs and one companion report were included in the analysis representing 165,703 patients. Our findings from 55 RCTs and 18 sub-group meta-analyses showed that complex implementation interventions with multiple components consisting of at least education + feedback + follow-up significantly increased the initiation of osteoporosis medications, and interventions with at least education + follow-up significantly increased the initiation of osteoporosis investigations. No significant impact was found for any type of intervention to reduce fracture. Complex interventions that include at least education + follow-up or feedback have the most potential for increasing osteoporosis investigations and treatment. Patient education appears to be an important component in osteoporosis disease management.