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The FDA has for agitation associated with Alzheimer's disease dementia, the agency announced on Thursday.

The new indication for brexpiprazole will make it the first FDA-approved treatment for this condition. The atypical antipsychotic was previously approved for treating major depressive disorder and schizophrenia.

"Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer's disease. 'Agitation' can include symptoms ranging from pacing or restlessness to verbal and physical aggression," said Tiffany Farchione, MD, director of the division of psychiatry in the FDA's Center for Drug Evaluation and Research, in a press release. "These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression."

In April, an advisory committee voted 9-1 in favor of the expanded indication. Advisors noted that the data presented at the meeting were sufficient to identify a population in whom the benefits of treatment outweighed its risks. While committee members largely agreed that this indication would benefit elderly patients, they did express concerns over the relatively limited safety data for the treatment.

Approval for the new indication was supported by efficacy demonstrated in two phase III studies, which evaluated fixed doses of brexpiprazole in patients with a probable diagnosis of Alzheimer's dementia. For eligibility, patients were required to have a score of 5 to 22 on the Mini-Mental State Examination.

Researchers found that treatment achieved a statistically significant reduction in agitation over a 12-week treatment period, based on the Cohen Mansfield Agitation Inventory (CMAI). Patients on either a 2-mg or 3-mg daily dose of brexpiprazole had improved CMAI scores versus placebo (treatment difference of -5.32, 95% CI -8.77 to -1.87, P=0.0026).

Another phase III study found that flexible dosing of brexpiprazole did not achieve statistical significance in reducing agitation scores at 12 weeks.

The trials also showed that brexpiprazole had a similar safety profile compared with the treatment's use in adults with schizophrenia and major depressive disorder. But notably, nine deaths occurred across the three phase III studies, with a disproportionate number in the brexpiprazole-treated groups.

will continue to carry a boxed warning about the risk of increased mortality in elderly patients with dementia-related psychosis treated with antipsychotic drugs. The warning further stipulates that the drug is not approved for patients with dementia-related psychosis who are not experiencing agitation associated with Alzheimer's dementia.

The drug is also not indicated as an "as-needed" therapy. The oral atypical antipsychotic is administered at a daily starting dose of 0.5 mg on days 1 to 7, increasing to 1 mg the following week and to the recommended target dose of 2 mg the week after (maximum 3 mg per day based on clinical response and tolerability).

While brexpiprazole's mechanism of action is unknown, efficacy "may be mediated through a combination of partial agonist activity at serotonin 5-HT_1A and dopamine D₂ receptors and antagonist activity at serotonin 5-HT_2A receptors," , Lundbeck and Otsuka.

The most common side effects with brexpiprazole among patients with agitation associated with dementia due to Alzheimer's disease include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances.

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