Keypoint: Brexpiprazole is safe and effective for reducing agitation associated with dementia due to Alzheimer Disease.
Treatment with brexpiprazole was associated with significant reductions in agitation among patients with dementia due to Alzheimer Disease (AD), according to study results presented at the American Association of Geriatric Psychiatry (AAGP) 2024 Annual Meeting, held in Atlanta, Georgia, from March 15 to 18, 2024.
For both patients and caregivers, the manifestation of agitation can be one of the most difficult symptoms to manage in dementia due to AD. Agitation often co-presents with psychosis symptoms and is typically an indication of accelerated disease progression. Consequently, there has been increased attention to potential pharmacological treatments for agitation and/or aggression in this patient population. To this aim, researchers are evaluating the efficacy and safety of brexpiprazole as a potential treatment option.
The researchers conducted a post hoc analysis of data from 2 separate 12-week, phase 3, randomized placebo-controlled trials to evaluate the use of brexpiprazole in patients with agitation associated with dementia due to AD. The primary outcome of interest was the change in Cohen-Mansfield Agitation Inventory (CMAI) Total score from baseline to week 12, and the researchers also assessed baseline psychosis using the Neuropsychiatric Inventory (NPI) delusion item and/or hallucination item score.
A total of 610 patients were evaluated, of which 363 patients received brexpiprazole (2 or 3 mg/day) and 247 received a placebo.1 The researchers reported that 142 patients had baseline psychosis while 465 were categorized into the patient subgroup without baseline psychosis.
At week 12, the mean change in CMAI score was greater among the patient group receiving brexpiprazole relative to the placebo group.1 Among patients with baseline psychosis, the researchers found that the mean change in CMAI score with use of brexpiprazole was significantly higher than placebo (-25.1 vs -19.1; P =.043).2 Treatment with brexpiprazole was similarly efficacious among the patient subgroup without baseline psychosis (-20.5) relative to placebo (-16.3; P =.0021).2 Additionally, brexpiprazole demonstrated greater reduction across all NPI outcome scores at week 12, compared with placebo.
Across each patient subgroup, the incidence of treatment-emergent adverse effects (TEAEs), serious TEAEs, and severe TEAEs were similar.2 The incidence of deaths was highest among patients with baseline psychosis taking brexpiprazole (1.3%) compared with placebo (0.0%) and relative to those without baseline psychosis (brexpiprazole:, 0.8%; placebo, 0.3%). All other adverse outcomes including sedation, incidence of falls, somnolence, TEAEs for cerebrovascular events, and TEAEs for cardiovascular events were less than 5% in both patient subgroups.
Investigators also conducted a systematic review and network meta-analysis to determine the most efficacious and safe pharmacological treatment for agitation in patients with dementia.4 Data were extracted from a total of 28 RCTs, 19 of which analyzed patients with dementia due to AD.
The investigators found that agitation/aggression was significantly lower among the groups taking brexpiprazole (mean difference [MD], -3.86; 95% CI, -6.03 to -1.12) and risperidone (mean difference [MD], -2.55; 95% CI, -4.70 to -0.57) relative to placebo. Brexpiprazole and risperidone were also more efficacious than memantine (MD, -7.65; 95% CI, -13.1 to -1.69 and MD, -6.37; 95% CI, -11.91 to -0.81) and haloperidol (MD, -5.6; 95% CI, -9.3 to -1.16 and MD, -4.28; 95% CI, -7.58 to -1.02) in improving agitation/aggression.
These study findings indicate that brexpiprazole is efficacious in reducing agitation and baseline psychosis across AD-related dementia patient subgroups. The abstract authors concluded, “Brexpiprazole showed larger improvement than placebo, and higher response rates based on a meaningful within-patient change threshold, regardless of dementia severity, presence or absence of co-occurring neuropsychiatric symptoms, use of concomitant treatments for dementia or psychiatric conditions, and care setting.”1
Study limitations include small sample sizes for certain subgroups and a lack of research on the long-term effects of these medications.
This article originally appeared on Psychiatry Advisor
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