FDA Approves First Non-Antipsychotic Drug to Treat Agitation Associated with Dementia

The U.S. Food and Drug Administration has approved an expanded use for Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets to treat agitation associated with dementia due to Alzheimer’s disease in adults. The drug is the first FDA-approved treatment for this condition that is not an antipsychotic. FDA initially approved Auvelity in 2022 to treat major depressive disorder in adults.

Bupropion

Dextromethorphan

"This approval represents a significant advancement in our ability to help patients and families dealing with one of the most challenging aspects of Alzheimer's disease," said FDA Commissioner Marty Makary, M.D., M.P.H. "With today’s action, patients and their families have access to an additional important treatment for complications of this devastating disease."

Agitation is a common and distressing symptom in patients with Alzheimer's disease dementia, characterized by excessive motor activity, or verbal or physical aggression. It can significantly impact quality of life for patients and caregivers. 

"Auvelity was found to be efficacious for treating agitation in Alzheimer’s disease in two randomized trials and now represents an additional option to address one of the most difficult sequelae of the disease, especially as it progresses,” said Tracy Beth Hoeg, M.D., Ph.D., Acting Director of the FDA’s Center for Drug Evaluation and Research. "We hope this approval will provide meaningful benefit to patients, their families, and caregivers."

The first randomized study (NCT 03226522) was a five-week trial in which participants received either Auvelity or a placebo.  The primary endpoint was the change from baseline to week five in the total score of the Cohen-Mansfield Agitation Inventory (CMAI), a survey that assesses the frequency of manifestations of agitated behaviors in elderly patients, based on caregiver reports. Auvelity was significantly superior to placebo in The Cohen-Mansfield Agitation Inventory score improvements.

The second randomized study (NCT 04947553) was a withdrawal study in participants who responded to Auvelity. Upon reaching a sustained clinical response to Auvelity, patients were randomly assigned to continue treatment with Auvelity or switch to placebo. The primary endpoint was time to relapse. Participants who continued Auvelity treatment had a significantly longer time to relapse of agitation symptoms compared to patients receiving the placebo. 

The most common side effects include dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating. Auvelity has a Boxed Warning about increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants. Health care providers should monitor patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during initial treatment. The medicine can cause seizures, with risk increasing with dose. It can also cause elevated blood pressure and hypertension, and may activate mania or hypomania (irritable mood) in susceptible patients.

Before starting Auvelity, health care providers should assess blood pressure, screen for personal or family history of bipolar disorder, and determine if patients are taking other medications containing bupropion or dextromethorphan. 

The FDA granted breakthrough therapy designation and priority review designation for this action. The approval of Auvelity for agitation associated with dementia due to Alzheimer's disease was granted to Axsome Therapeutics.

https://en.wikipedia.org/wiki/Bupropion

https://en.wikipedia.org/wiki/Dextromethorphan

Caffeine can prevent memory loss in diabetes

Caffeine can prevent memory loss in diabetes: Badly controlled diabetes are known to affect the brain causing memory and learning problems and even increased incidence of dementia, although how this occurs is not clear. But now a study in mice with type 2 diabetes has discovered how diabetes affects a brain area called hippocampus causing memory loss, and also how caffeine can prevent this. 

Protective properties of green tea uncovered

In continuation of my up date on the benefits of green tea...

Protective properties of green tea uncovered

Ref : doi:10.1016/j.phymed.2010.11.004

Donepezil hydrochloride for Dementia Related to Alzheimer's Disease...

We know that, ARICEPT® [donepezil hydrochloride, see structure  (source-chemSpider) ] is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2,3-dihydro-5,6-dimethoxy-2 -[[1-(phenylmethyl)-4-piperidinyl]- methyl]-1H-inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020.

Acetylcholinesterase is the target of many Alzheimer's Dementia drugs , nerve gases, particularly the organophosphates (e.g. Sarin) and insecticides (e.g. carbaryl). These agents — known as cholinesterase inhibitors — block the function of acetylcholinesterase and thus cause excessive acetylcholine to accumulate in the synaptic cleft. The excess acetylcholine causes neuromuscular paralysis (i.e. interminable muscle contractions) throughout the entire body, leading to death by asphyxiation.

The U.S. Food and Drug Administration approved the first generic versions of Aricept (donepezil hydrochloride) orally disintegrating tablets on Dec. 11. Donepezil hydrochloride is indicated for the treatment of dementia related to Alzheimer's disease. Orally disintegrating tablets dissolve on the tongue, without having to be swallowed whole. This may make it easier to take the medication for older or disabled patients who have difficulty swallowing.

Alzheimer's disease :

Alzheimer's disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks of daily living. In most people with Alzheimer's disease, symptoms first appear after age 60. Alzheimer's disease is the most common cause of dementia among older people, but it is not a normal part of aging...

Ref : http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm