What is Agitation in Alzheimer’s?
New drug trial tests medication that could provide relief
Charter Research’s clinic trial center in Orlando is seeking candidates for a drug trial aimed at one of the most common and vexing symptoms: agitation in Alzheimer’s. The medication, ITI-1284 from Intra-Cellular Therapies, holds promise of relieving agitation, which appears in 40%-60% of Alzheimer patients and in 75% of moderate to severe dementia sufferers.
What is agitation in Alzheimer’s?
Agitation in all its forms—from finger tapping, nail biting and restlessness to excessive motor activity, verbal aggression, and physical aggression—is particularly challenging because there are currently no effective treatments for it, said Dr. Edgardo Rivera, Charter’s medical director in Orlando.
“It may be very difficult to deal with some of these patients,” he said. “They encounter problems with daily living earlier than patients who are not agitated. These patients tend to be moved to nursing homes earlier.”
This can have an added emotional toll on both the patient and caregiver. “Making the decision to move the patient into a care facility takes an increased toll on the patient, but also on the caregiver because they may want to continue caring for their loved one,” Rivera said. “But they don’t have the physical stamina, the knowledge, or the tools to do that.”
In addition, myriad conditions associated with the Alzheimer’s may cause agitation—from sleep disorders to depression to delusions. Doctors and caregivers often turn to non-pharmacological maneuvering or distractions to get patients out of their agitated states.
Current Agitation Treatments
When drug treatments are used to control the issues, doctors prescribe medication to treat the underlying cause of the agitation—if it is known. For example, sedatives can help address sleeping disorders, Rivera said. However, Alzheimer patients often cannot articulate a cause for their apprehension or agitation. Neuroleptics, a class of drugs used to treat and manage symptoms associated with various psychiatric disorders, can be prescribed, but there are disadvantages to those as well.
“Those medications may work on some people, but may increase mortality in others,” Rivera said. “You may have to decide whether the increased mortality is a risk that you want to take versus the benefit that the medicine may give you from a quality-of-life perspective. So, it is a difficult conundrum.”
This is why the ITI-1284 trial should be of interest to anyone affected by Alzheimer’s. An effective agitation treatment could shift the caregiver paradigm immensely.
“If we had something that would be effective and be able to care for patients without the added stress of having to deal with an agitated person, it would be much, much better for the caregivers.”
The Trial Process
The trial at Charter’s Orlando facility—one of 70 research centers around the world participating in the study—aims to establish the efficacy, safety, and tolerability of ITI-1284 in Alzheimer’s patients with agitation. There will be approximately 320 patients across all testing centers.
A four-week screening period to assess patient eligibility includes diagnostic and physical examinations. Patients whose agitation is attributable to medications, substance abuse, or active medical or psychiatric conditions in the investigator’s judgement will not be eligible to participate.
The trial, double-blinded and placebo-controlled, means doctors and patients won’t know if the group they are assigned to is receiving the medication or a placebo. Participants take a daily quick dissolving tablet placed under the tongue (sub-lingual). They check in weekly for 12 weeks, alternating between phone check ins or clinic visits beginning three weeks after the initial dose.
Under the trial protocol, dosing will begin with 10 mg daily and increase to 20 mg daily after the first or second week of treatment. Patients who have tolerability reactions are kept on the lower dosage for the entire 12-week treatment period.
A 30-day safety period follows the treatment period, which includes an in-person visit. The maximum duration of the study will be approximately 21 weeks.
Caregiver Candor
Rivera adds one of the key characteristics of the screening process will involve assessing the candor of a patient’s caregiver and getting them to relate objectively what they observe.
“We depend on caregivers to provide the information we’re looking for,” he said. “We need them to be extra vigilant in this.”
But it is common for caregivers to try to explain or downplay patient behavior, Rivera said. “They will say something like, ‘Well, he’s like that today because he ate something yesterday that didn’t agree with him.’”
This misguided mindset, even if well intentioned, could lead to potentially significant changes in patient behavior being missed, overlooked, or explained away.
“The person who is taking care of them on a regular basis will know exactly the symptoms we’re looking for, and we rely on them to provide that information to us,” he said. “So, we need an honest assessment from the caregiver. We don’t want them to be under or over reporting, just provide the raw information, and we will process that information accordingly.”
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