“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.
He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions.
“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained.
The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist.
“These medications can help reduce the risk of agitation,” Dr. Finney said.
“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added.
Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication.
The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.
“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association.
Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”
The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.
A version of this article appeared on Medscape.com.