How prazosin works
Alzheimer’s disease is a neurodegenerative disorder that results in a slow decline in memory and reasoning abilities as it progresses. One of the symptoms associated with the disease is an increase in agitated and aggressive behaviors. These symptoms are treated with antipsychotic medications, but in many cases, these are ineffective or can have harmful side effects.
Nerve cells normally communicate with each other using chemical messengers called neurotransmitters. Neurotransmitter levels are tightly regulated, and only certain cells can pick up these messages as neurotransmitters can only interact with specific receptors found on the outside of these cells, like a key only fitting a particular lock.
Norepinephrine, a neurotransmitter that frequently malfunctions in Alzheimer’s patients, is involved in many functions in the brain including inflammation, immune response, and memory. Norepinephrine normally interacts with the alpha-1 adrenoreceptor (AR). It is thought that an increase in the activation of AR might cause the increased aggression and agitation seen in Alzheimer’s patients.
Prazosin is part of a class of drugs called alpha-blockers. It competes with norepinephrine to bind to the AR, resulting in its reduced activation. This could potentially lead to less aggression in Alzheimer’s patients.
Prazosin in clinical trials
The effectiveness of prazosin in patients with moderate Alzheimer’s disease has been assessed in several clinical trials.
A randomized, placebo-controlled study (NCT00161473) in 24 patients took place over nine weeks in a Seattle nursing home. The patients were assessed in the first, second, fourth, sixth, and eighth weeks for changes in behavior using a number of psychiatric assessment scales. The results, published in The American Journal of Geriatric Psychiatry, suggested that prazosin significantly reduced the level of agitation and aggression in Alzheimer’s disease patients, compared with the placebo-treated group.
A second clinical trial (NCT01126099) assessing prazosin over a 12-week period compared with placebo has also been completed. Results of this trial also showed an improvement in the behavior of patients treated with prazosin. The results of the two studies have been summarized in an article published in the journal Alzheimer’s & Dementia.
A case study published in the Journal of Clinical Gerontology and Geriatrics described an elderly man with dementia who was given prazosin after all other options were tried. He showed a significant reduction in agitation, aggression, and physical violence following treatment, and the medication was well-tolerated. The authors emphasized, however, that current data is limited and that there is a need for larger clinical trials to verify these findings.
A double-blind, randomized, placebo-controlled Phase 2 study (NCT03710642) called PEACE-AD aims to recruit 186 participants in the U.S. as part of the Alzheimer’s disease cooperative study (ACDS). Two-thirds of the participants will receive prazosin and the other third will receive a placebo for 12 weeks during which they will be monitored for any changes in disruptive behaviors using the ADAS-clinical global impression of change in agitation.
Last updated: Sept. 9, 2019
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