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Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis.
BMC Geriatr. 2020 Jun 16; 20(1):212.BG

Abstract

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.

Authors+Show Affiliations

Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada. jennifer.watt@utoronto.ca. Division of Geriatric Medicine, Department of Medicine, University of Toronto, 190 Elizabeth Street, R. Fraser Elliott Building, 3-805, Toronto, Ontario, M5G 2C4, Canada. jennifer.watt@utoronto.ca.Division of Geriatric Medicine, Department of Medicine, University of Toronto, 6 Queen's Park Cres W, Toronto, Ontario, M5S 3H2, Canada. Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada. O'Brien Institute of Public Health, University of Calgary, 3280 Hospital Dr NW, Calgary, Alberta, T2N 4Z6, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada. Department of Primary Education, School of Education, University of Ioannina, 45110, Ioannina, Greece. Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College, W12 0NN, London, UK.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada. Institute for Health Policy, Management and Evaluation, University of Toronto, 4th floor, 155 College St, Toronto, Ontario, M5T 3M6, Canada.Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1W8, Canada. Division of Geriatric Medicine, Department of Medicine, University of Toronto, 190 Elizabeth Street, R. Fraser Elliott Building, 3-805, Toronto, Ontario, M5G 2C4, Canada. Institute for Health Policy, Management and Evaluation, University of Toronto, 4th floor, 155 College St, Toronto, Ontario, M5T 3M6, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32546202

Citation

Watt, Jennifer A., et al. "Safety of Pharmacologic Interventions for Neuropsychiatric Symptoms in Dementia: a Systematic Review and Network Meta-analysis." BMC Geriatrics, vol. 20, no. 1, 2020, p. 212.
Watt JA, Goodarzi Z, Veroniki AA, et al. Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis. BMC Geriatr. 2020;20(1):212.
Watt, J. A., Goodarzi, Z., Veroniki, A. A., Nincic, V., Khan, P. A., Ghassemi, M., Thompson, Y., Lai, Y., Treister, V., Tricco, A. C., & Straus, S. E. (2020). Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis. BMC Geriatrics, 20(1), 212. https://doi.org/10.1186/s12877-020-01607-7
Watt JA, et al. Safety of Pharmacologic Interventions for Neuropsychiatric Symptoms in Dementia: a Systematic Review and Network Meta-analysis. BMC Geriatr. 2020 Jun 16;20(1):212. PubMed PMID: 32546202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis. AU - Watt,Jennifer A, AU - Goodarzi,Zahra, AU - Veroniki,Areti Angeliki, AU - Nincic,Vera, AU - Khan,Paul A, AU - Ghassemi,Marco, AU - Thompson,Yuan, AU - Lai,Yonda, AU - Treister,Victoria, AU - Tricco,Andrea C, AU - Straus,Sharon E, Y1 - 2020/06/16/ PY - 2020/01/30/received PY - 2020/06/08/accepted PY - 2020/6/18/entrez PY - 2020/6/18/pubmed PY - 2020/6/18/medline KW - Dementia KW - Harm KW - Meta-analysis KW - Network meta-analysis KW - Neuropsychiatric symptoms KW - Systematic review SP - 212 EP - 212 JF - BMC geriatrics JO - BMC Geriatr VL - 20 IS - 1 N2 - 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. SN - 1471-2318 UR - https://www.unboundmedicine.com/medline/citation/32546202/Safety_of_pharmacologic_interventions_for_neuropsychiatric_symptoms_in_dementia:_a_systematic_review_and_network_meta-analysis L2 - https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-020-01607-7 DB - PRIME DP - Unbound Medicine ER -
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