A drug called brexpiprazole that’s normally used to treat symptoms of schizophrenia and major depressive disorders has been found to reduce agitation in older adults with Alzheimer’s disease.
A phase III clinical study led by Otsuka Pharmaceutical and H. Lundbeck A/S specifically discovered that patients who received two fixed doses of brexpiprazole (2 mg/day or 3 mg/day) had a significantly greater reduction in agitation compared to a placebo.
“There are no Food and Drug Administration (FDA) approved medications, not just for agitation, but for any of the symptoms of Alzheimer’s disease,” said George Grossberg, MD, professor of geriatric psychiatry at Saint Louis University. “So, this has the potential to become the first FDA-approved treatment for agitation in patients with Alzheimer’s disease.”
…this has the potential to become the first FDA-approved treatment for agitation in patients with Alzheimer’s disease.
According to a news release from Otsuka, the 12-week trial included 345 male and female patients, aged 55 to 90, with a diagnosis of probable Alzheimer’s disease and also met the criteria for agitation as defined by the International Psychogeriatric Association.
While the full study results are not yet available, the trial established there was a change in the Cohen-Mansfield Agitation Inventory score – a 29-item scale used to systematically assess agitation – at week 12 for all patients treated with brexpiprazole compared to those treated with placebo.
In addition, the study found that brexpiprazole was generally well tolerated and “no new safety signals were observed.” The only adverse reaction was a headache, experienced in 6.6% of participants who received brexpiprazole.
What else you need to know about brexpiprazole
Brexpiprazole, also sold under the brand name Rexulti, is an FDA-approved medication meant to treat two conditions—the first being for people who are depressed or have major depressive disorders.
“People who are depressed are maybe on an antidepressant or a mood elevator. Perhaps they’re a little bit better, but not as well as we’d like,” Grossberg explained. “We can add brexpiprazole as an augmenting agent as something that can work together with the mood elevator or the antidepressant to help improve their quality of response relative to their depression.”
The second FDA-approved use is to treat symptoms of psychosis including hallucinations and delusions in schizophrenia.
“Patients with schizophrenia who are hearing voices, seeing things or imagining things that you may not see, brexpiprazole is considered an effective and safe antipsychotic,” he added.
According to Amber Dixon, a dietitian, geriatric nurse and CEO of Elderly Assist Inc., brexpiprazole works by binding to dopamine and serotonin receptors in the brain, which helps to decrease abnormal activity in the brain. Common side effects include weight gain, headache, dizziness and nausea.
“Brexpiprazole can also cause raised prolactin levels, which can lead to sexual side effects such as decreased libido and erectile dysfunction,” she said. “In rare cases, it may also cause movement disorders such as tardive dyskinesia.”
She added that brexpiprazole should be used with caution in people with a history of stroke or heart disease.
What this means for people with Alzheimer’s
For people who have Alzheimer’s, agitation is one of the leading causes of institutionalization, such as placement in nursing homes or assisted living facilities, Grossberg said.
“It’s one of the leading causes of why families who are very dedicated to their loved one with Alzheimer’s disease kind of throw in the towel and say, ‘I just can’t do it anymore,’” he said.
While brexpiprazole is not a treatment for the disease, it’s meant for the most common difficult symptom, which Grossberg said affects 60% to 80% of Alzheimer’s patients at some point.
“When we talk about agitation, it’s a spectrum,” he explained. “We go from mild irritability to more agitated behavior to overtly aggressive behavior. They cause tremendous distress, not just for the patient, but also for the family and for the caregivers.”
Because there’s no FDA-approved medication for symptoms of agitation in those with Alzheimer’s, brexpiprazole has the potential to give patients and families optimism that something in the future may be able to help.
“It provides patients and families hope,” Grossberg said. “It provides the hope that they can continue to manage that individual with Alzheimer’s disease and continue to take care of them at home longer, and try to prevent institutionalization as long as possible.”
He added if brexpiprazole received FDA approval, it may enable assisted living facilities or nursing homes to keep the patient and treat them in place for agitation, rather than sending them to the hospital.
“We know that hospitalization is not a good outcome for this older, kind of frail population with Alzheimer’s disease, who often have a variety of comorbid medical problems that kind of come with the territory of being in your 80s or 90s,” he said.
What comes next
Before brexpiprazole can be used to treat agitation, officials from Otsuka and Lundbeck noted it will need FDA approval.
“Brexpiprazole is currently in the clinical trial, and we do not expect the full data to be released until next year,” a spokesperson from Otsuka said in an email response.
Grossberg said the next step is for both pharmaceutical companies to gather data from two large placebo-controlled trials and submit that together with safety and tolerability data to the FDA. Otsuka stated they’re planning a regulatory filing to the FDA later in 2022.
“They appear to have all their ducks in order, but whether it’s gonna be approved or not is not my decision,” Grossberg said. “However, if they meet all the criteria and if the FDA agrees, then I imagine this drug will be approved sometime next year.”