Brexpiprazole for the treatment of agitation in Alzheimer Dementia

Brexpiprazole is an atypical antipsychotic that acts on noradrenergic, serotonergic, and dopaminergic neurotransmitter systems, which are implicated in the neurochemistry of agitation in Alzheimer disease (1)

• brexpiprazole has less intrinsic activity (ie, is less of a partial agonist and more of an antagonist) at D2 receptors than aripiprazole - brexpiprazole also has much more potent actions at 5HT2A, 5HT1A, and alpha 1B receptors than aripiprazole

Brexpiprazole in Alzheimer dementia (1):

• randomized clinical trial with 345 patients, brexpiprazole, 2 mg/d or 3 mg/d, demonstrated a statistically significant reduction in agitation (Cohen-Mansfield Agitation Inventory score) vs placebo over 12 weeks. No treatment-emergent adverse events had an incidence of 5% or greater with brexpiprazole and greater than placebo, and the discontinuation rates due to adverse events were similar across the groups
  
  
• brexpiprazole, 2 or 3 mg, reduced agitation in Alzheimer dementia and was generally well tolerated over 12 weeks

Study authors concluded that "..Overall, brexpiprazole, 2 or 3 mg, appears to have a favorable benefit/risk profile in the treatment of agitation in Alzheimer dementia. Based on the results of this trial, together with a previous trial, brexpiprazole was approved in the United States for the treatment of agitation associated with dementia due to Alzheimer disease.."

Reference:

1. Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. Published online November 06, 2023. doi:10.1001/jamaneurol.2023.3810