Brexpiprazole improves agitation in patients with Alzheimer’s dementia over 12 weeks
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Key takeaways:
- Adults with agitation in Alzheimer’s dementia were randomized to brexpiprazole or placebo for 12 weeks.
- Patients on brexpiprazole had greater reduction in agitation from baseline to week 12 vs. those on placebo.
Treatment with brexpiprazole 2 mg or 3 mg resulted in significant reduction in agitation over 12 weeks compared with placebo in adults with Alzheimer’s dementia, according to research published in JAMA Neurology.
“One of the most challenging aspects of caring for someone with Alzheimer’s dementia, whether by a health care provider or a loved one, is when the patient develops agitation symptoms that become increasingly difficult to manage,” George T. Grossberg, MD, senior study author and Samuel W. Fordyce Professor and director of geriatric psychiatry at Saint Louis University School of Medicine, told Healio in an email. “Agitation associated with dementia due to Alzheimer’s disease affects nearly 50% of patients.”
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Grossberg and colleagues aimed to confirm the safety, efficacy and tolerability of brexpiprazole in adults aged 55 to 90 years with agitation in Alzheimer’s dementia.
Their phase 3 multicenter, randomized, double-blind, fixed-dose, parallel-arm study was conducted from May 2018 to June 2022 at 123 sites in Europe and the United States. A total of 345 individuals (mean age, 74 years; 56.5% women) were randomized 2:1 to receive brexpiprazole (n = 228) or placebo (n = 117) for 12 weeks, with those in the treatment cohort further randomized to receive fixed doses of either 2 mg per day or 3 mg per day in a 1:2 ratio.
The primary study endpoint was change in Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline to week 12 for brexpiprazole, 2 mg or 3 mg, compared with placebo, with safety assessments made by standard measures including treatment-emergent adverse events.
According to results, completion rates were 86.8% for brexpiprazole and 88.9% for placebo. Researchers reported statistically significant improvement in the brexpiprazole group compared with those given placebo in CMAI total score (brexpiprazole baseline, 80.6, mean change, −22.6; placebo baseline, 79.2, mean change, −17.3; least-squares mean difference = −5.32; 95% CI, −8.77 to −1.87).
Data further showed that the incidence of treatment-emergent adverse events was no greater than 5% with brexpiprazole nor greater than placebo. The percentage of participants who discontinued the study because of adverse events was 5.3% for brexpiprazole and 4.3% for placebo.
“[This publication] is the first to report the efficacy of brexpiprazole to significantly improve each of three classifications of agitation symptoms: aggressive behaviors, physically nonaggressive behavior and verbally agitated behavior,” Grossberg told Healio. “This evidence will help clinicians, families and caregivers make informed decisions about what is best for their patient or loved one who lives with this complex condition.”
In a related editorial, Clive Ballard, MD, PhD, professor of age-related diseases at University of Exeter Medical School in the United Kingdom, cited the timeliness of the study, as treatment for agitation continues to be a high priority yet pharmacological solutions are few.
“Treatment of agitation and aggression is challenging,” he wrote in JAMA Neurology. “Evidence-based best practice guidelines recommend that nonpharmacological interventions are often effective and should be considered and attempted prior to pharmacological treatments.”