FDA Approves Rexulti for Agitation Associated With Dementia Due to Alzheimer’s Disease

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Back to table of contents Next article Clinical & ResearchFull AccessFDA Approves Rexulti for Agitation Associated With Dementia Due to Alzheimer’s DiseaseMark MoranMark MoranSearch for more papers by this authorPublished Online:12 May 2023https://doi.org/10.1176/appi.pn.2023.07.7.17AbstractOne expert called the approval a “positive step” for the treatment of agitation associated with dementia in Alzheimer’s but cautioned against using the drug as a panacea for all behavioral symptoms of dementia.The U.S. Food and Drug Administration (FDA) this week approved the expanded use of Rexulti (brexpiprazole) for the treatment of agitation associated with dementia due to Alzheimer’s disease (AD).“Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric symptom that is reported in approximately half of all patients with Alzheimer’s dementia,” wrote Otsuka Pharmaceutical Co. Ltd. and Lundbeck LLC, makers of the medication, in a press release. The symptoms cover “a large group of behaviors occurring in patients with Alzheimer’s disease, such as pacing, gesturing, profanity, shouting, shoving, and hitting.”Brexpiprazole was first approved by the FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder and as a treatment for adults with schizophrenia. In 2021, the FDA expanded the use of the medication for the treatment of adolescents over the age of 13 with schizophrenia. Earlier this year, Otsuka and Lundbeck announced that the FDA would review the companies’ supplemental New Drug Application for brexpiprazole for the treatment of agitation associated with AD.In a hearing last month, the FDA’s Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee voted 9-1 in favor of the approval of brexpiprazole for the new indication, noting the data presented by Otsuka and Lundbeck suggested that the benefits of the medication outweighed the risks for patients with these symptoms.A briefing document released prior to the April FDA hearing describes some of the data presented by the manufacturers, including several phase 3, 12-week, randomized, placebo-controlled studies. “Results from Studies 331-12-283 and 331-14-213 suggest that brexpiprazole exhibited a statistically significant treatment effect in the reduction of agitation over a 12-week treatment period, while also showing a similar safety profile relative to its use in adults with schizophrenia and major depressive disorder,” the document stated. “[B]rexpiprazole’s effect on mortality appears to be consistent with the known risk with other antipsychotics in elderly patients with dementia.”Rajesh Tampi, M.D., M.S., said it is important that physicians determine the cause of agitation in patients with Alzheimer’s disease before prescribing Rexulti.The approval of Rexulti “is a positive step for the treatment of agitation associated with dementia related to Alzheimer’s Disease,” said Rajesh Tampi, M.D., M.S., a professor and chair of the Department of Psychiatry at Creighton University and a past president of the American Association for Geriatric Psychiatry. “This is the first drug to be approved for agitation. The manufacturers were persistent and had solid data to support efficacy,” he told Psychiatric News.Tampi cautioned that agitation is just one of many noncognitive behavioral symptoms of dementia that patients may experience. “Brexpiprazole should absolutely not be assumed to treat all of those symptoms,” he said. “For instance, the most important behavioral symptom of dementia is apathy, and brexpiprazole should not be used to treat apathy.”He noted that only a minority of patients with dementia are treated by geriatric psychiatrists; most see their primary care physician (or other physicians who are not psychiatrists) for care. “My worry is that some will use the medication as a panacea for every behavioral symptom,” he said.According to the updated medication label, Rexulti is to be taken daily. The medication is not approved for the treatment of Alzheimer’s patients with dementia-related psychosis without agitation.“Physicians need to make a good assessment of whether the agitation is a result of dementia related to AD or due to other causes—for example, a medical condition or a psychiatric condition like bipolar disorder or schizophrenia,” Tampi said.Inappropriate use of brexpiprazole “will only raise the risk of adverse events associated with antipsychotic treatments—sedation, risk of falls, stroke and death,” he said.The most common side effects of Rexulti reported during the clinical trials by patients with agitation associated with dementia due to Alzheimer’s disease include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances, according to an FDA release. “Rexulti will retain the Boxed Warning for medications in this class that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death,” the agency noted. ■ResourcesFDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer’s DiseaseFDA Briefing Document ISSUES NewArchived