OBJECTIVES:

In agitated older adults with dementia who are threatening to harm themselves or others, pharmacological treatments are recommended when first-line non-pharmacological strategies are ineffective. However, with newer clinical trials available, there is a need to provide current evidence of these pharmacological agents' relative efficacy. To determine the most efficacious pharmacological treatment for agitation and aggression in patients with dementia.

METHODS:

A systematic search was performed on MEDLINE®/PubMed, Ovid EMBASE®, and Cochrane Library (CENTRAL, Cochrane DSR) to identify relevant articles published from the inception of each database to August 2022. We included randomized controlled trials (RCTs) of patients with dementia who are agitated and/or aggressive and require pharmacological treatment. Two independent reviewers screened titles, abstracts, and full texts of all identified articles to determine eligibility for inclusion in the systematic review and network meta-analysis (NMA). We conducted a random-effects NMA to estimate pooled relative standardized mean differences in agitation and/or aggression measures (based on Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI]-agitation and aggression sub scores) and their 95% confidence intervals (CI).

RESULTS:

Thirty-two RCTs consisting of 13264 patients (66% female; mean age, 79.75 (8.74) were included in the NMA. Aripiprazole (SMD: -0.707; 95% CI: -1.314 to -0.100) and risperidone (SMD: -0.487 95% CI: -0.924 to -0.049) were found to be significantly more efficacious than placebo. In addition, although not significant, point estimates suggest that there could be an improvement in agitation and/or aggression across all drugs compared to the placebo except for quetiapine, memantine, donepezil, and haloperidol.

CONCLUSIONS:

Aripiprazole and risperidone demonstrated significant improvement in agitation in patients with dementia. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this NMA.