Alzheimer’s disease is a progressive neurodegenerative disorder characterized by the formation of protein plaques or clumps in the brain. Although memory loss and cognitive function decline are well-known symptoms of Alzheimer’s disease, patients also often experience neuropsychiatric symptoms such as agitation.
Managing symptoms of agitation
Agitation is reported in about 50% of patients with Alzheimer’s disease. Aggressive behavior, irritability, disinhibition, and emotional distress are some of the features of agitation. The cause of agitation in Alzheimer’s disease patients is unclear, but the imbalance in neurotransmitter levels (cell signaling molecules in the nervous system) and their impact on brain cell communication may play a role.
The patient’s healthcare team, along with a trained therapist or psychiatrist, can help them and their caregivers cope with agitation. Coping strategies include:
- Developing a routine for daily activities such as bathing, dressing, and eating.
- Reducing clutter and noise.
- Speaking calmly.
- Scheduling daily quiet times.
- Incorporating daily relaxation techniques such as breathing exercises, soothing music, or walks.
Treating agitation
In severe cases, patients may require medications to manage their agitation. Currently, no anti-agitation treatments are approved specifically for Alzheimer’s disease. However, the doctor may prescribe antipsychotics or antidepressants.
A few experimental treatments are being evaluated to manage agitation in Alzheimer’s disease patients, including:
AXS-05
AXS-05 is an investigational therapy being developed by Axsome Therapeutics. AXS-05 is a combination of two medications, bupropion and dextromethorphan, both of which function to improve the activity of neurotransmitters in the brain. A Phase 2/3 trial (NCT03226522) called ADVANCE-1 is underway to evaluate the safety and efficacy of AXS-05 in Alzheimer’s patients. This multicenter study plans to recruit 435 Alzheimer’s patients from 65 to 90 years old at 62 study locations across the U.S.
AVP-786
Avanir Pharmaceuticals’ AVP-786 is an experimental therapy to treat agitation in Alzheimer’s disease patients. It is a combination of dextromethorphan, quinidine, and deuterium. Quinidine and deuterium prolong dextromethorphan’s activity by preventing its breakdown in the body. Several clinical studies are evaluating the safety and efficacy of AVP-786 in Alzheimer’s patients.
Brexpiprazole
Brexpiprazole, co-developed by Otsuka Pharmaceutical and Lundbeck, is a potential anti-agitation therapeutic for patients with Alzheimer’s disease and associated dementia. Brexpiprazole’s mechanism of action is unclear, but it is thought to function by modulating the levels of the two neurotransmitters, serotonin and dopamine. Approved by the U.S. Food and Drug Administration to treat schizophrenia, brexpiprazole is being evaluated in Alzheimer’s patients in multiple clinical trials.
Prazosin
Prazosin functions by blocking the activation of signaling molecules that increase agitation. This alpha-blocker is approved for the treatment of high blood pressure. Two clinical trials (NCT00161473 and NCT01126099) showed that prazosin significantly lowered agitation and aggression in patients with Alzheimer’s disease. An ongoing Phase 2 study (NCT03710642) is now evaluating the safety and efficacy of prazosin compared with a placebo in Alzheimer’s patients.
Last updated: Oct. 14, 2019
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