Watt JA, Goodarzi Z, Veroniki AA, et al. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2019 Oct 15. pii: 2753018. doi: 10.7326/M19-0993. (Systematic review)

Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia.

Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia.

Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews.

Study Selection: Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia.

Data Extraction: Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias.

Data Synthesis: After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95% credible interval {CrI}, -0.99 to -0.01]), massage and touch therapy (SMD, -0.75 [CrI, -1.12 to -0.38]), and music combined with massage and touch therapy (SMD, -0.91 [CrI, -1.75 to -0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, -0.29 [CrI, -0.57 to -0.01]) was statistically but not clinically more efficacious than usual care.

Limitations: Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated.

Conclusion: Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia.

Primary Funding Source: Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130).

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Neurology 6 / 7
Internal Medicine 6 / 7
Geriatrics 6 / 7
Physical Medicine and Rehabilitation Coming Soon...
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

Article is most relevant to hospitalists and SNFists; less relevant to primary care physicians who don`t provide care in these settings. A network diagram is used that is not a familiar tool nor really explained.

General Internal Medicine-Primary Care(US) rater

Interesting interventions for aggressive and agitated behavior in persons with dementia. It mirrors my anecdotal and clinical experience and should inform a "less is more" approach when it comes to using psychoactive drugs in folks who suffer from dementia.

Geriatrics rater

These results confirm that non-pharmacologic approaches should become standard of practice.

Geriatrics rater

This is a complex and ambitious network meta-analysis (NMA) of 163 studies comparing the efficacy of non-pharmacologic and pharmacologic interventions for physical and verbal aggression and physical and verbal agitation in 23,143 patients with dementia. The sample size was large enough to compare the efficacy of a variety of non-pharmacologic and pharmacologic interventions, using consensus-developed criteria for minimal improvement. The results (summarized in Figure 3) suggest that antipsychotics, which in the US have a black box warning for increasing the risk for mortality of older dementia patients and are associated with falls, sedation, and extra-pyramidal side-effects, should not be first-line therapy for dementia-related agitation and aggression. The one area in which pharmacotherapy (anticonvulsants) proved superior was in the realm of verbal agitation. Of note, typical antipsychotics showed overall low benefits, and atypical antipsychotics emerged as poorly effective except for verbal agitation, for which they were less effective than anticonvulsants. The take-home message is that there is little role for antipsychotics in the management of agitation and aggression despite the high prevalence of use for these indications. The studies, however, were at high risk for bias due to missing data on the dominant outcome variable, subsets of the Cohen-Mansfield Agitation Inventory, as well as representing mostly women in nursing homes = age 80. This bias substantially decreases the generalizability of the results, but they nonetheless underscore that non-pharmacologic approaches that involve physical activities (outdoor activities in particular) and massage and touch therapy may be relatively the most successful. Because it is a meta-analysis, the study does not attempt to evaluate efficacy by whether agitation (and also aggression) appear driven by hallucinations, delusions, or anxiety/depression. Another limitation is that the study does not include antidepressants among the pharmacologic agents studied despite the positive effect of citalopram in reducing the severity of agitation in dementia patients.
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