Donanemab-azbt (Kisunla – Lilly), an IV amyloid beta-directed monoclonal antibody, has been approved by the FDA for treatment of Alzheimer's disease (AD). The label states that the drug should only be started in patients with mild cognitive impairment (MCI) or mild dementia. Donanemab is the third IV amyloid beta-directed monoclonal antibody to be marketed in the US. Lecanemab (Leqembi – Biogen/Eisai) was approved by the FDA in 2023 for the same indication as donanemab. Aducanumab (Aduhelm – Lilly) was granted accelerated approval in 2021, but it was withdrawn from the market earlier this year for commercial reasons.

View the Table: Amyloid-Directed Antibodies for Alzheimer's Disease

AD-Detect (Quest), a blood test to evaluate Alzheimer's disease risk, is being marketed directly to consumers. It has not been cleared or approved by the FDA (laboratory-developed tests like this one currently do not need FDA authorization to be marketed).

Lecanemab-irmb (Leqembi – Eisai/Biogen), the IV amyloid-directed monoclonal antibody that received accelerated approval from the FDA in January 2023 for treatment of early Alzheimer's disease, has now received full approval from the FDA based on a trial showing that it slowed cognitive and functional decline in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease dementia and confirmed presence of brain amyloid. The IV amyloid-directed monoclonal antibody aducanumab (Aduhelm) has received only an accelerated FDA-approval for the same indication.

The FDA has approved the oral second-generation antipsychotic drug brexpiprazole (Rexulti – Otsuka/Lundbeck) for once-daily treatment of agitation associated with dementia due to Alzheimer's disease (AD). Brexpiprazole is the first drug to be approved in the US for this indication. It is also approved for treatment of schizophrenia and as an adjunct to antidepressants for treatment of major depressive disorder.

Lecanemab-irmb (Leqembi – Biogen/Eisai), an IV amyloid beta-directed monoclonal antibody, has received accelerated approval from the FDA for treatment of Alzheimer's disease. The label states that treatment with Leqembi should be initiated in patients with mild cognitive impairment (MCI) or mild dementia, the population in which the drug was initiated in clinical trials. Lecanemab is the second IV amyloid-beta directed monoclonal antibody to be approved for this indication; aducanumab (Aduhelm) was approved in 2021 and has the same restrictions on treatment initiation.

The FDA has approved an extended-release fixed-dose combination of dextromethorphan and bupropion (Auvelity – Axsome) for treatment of major depressive disorder (MDD) in adults.

A reader asked us to review use of the phosphodiesterase-5 (PDE5) inhibitor sildenafil for treatment of Alzheimer's disease (AD).

Alzheimer's disease (AD) is the most common cause of dementia, but cognitive decline is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

View the Comparison Table: Drugs for Alzheimer's Disease

A once-weekly transdermal formulation of the acetylcholinesterase inhibitor donepezil (Adlarity – Corium) has been approved by the FDA for treatment of mild, moderate, and severe Alzheimer's disease (AD) dementia. Donepezil is the second acetylcholinesterase inhibitor to become available in a transdermal formulation; transdermal rivastigmine (Exelon Patch), which is applied once daily, has been available for years for the same indication. Donepezil is also available in oral formulations (Aricept, and generics) for treatment of AD dementia.

In June 2021, the FDA approved the IV amyloid beta-directed monoclonal antibody aducanumab (Aduhelm) for treatment of Alzheimer’s disease. The approval did not restrict use of the drug to patients with mild cognitive impairment or mild dementia, which was the population enrolled in the clinical trials. Now, Biogen, with the permission of the FDA, has made an addition to the labeling of the drug that says: Treatment with Aduhelm should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.

Aducanumab-avwa (Aduhelm – Biogen/Eisai), an IV amyloid beta-directed monoclonal antibody, has received accelerated approval from the FDA for treatment of Alzheimer's disease. The approval was based on the surrogate endpoint of reduction in amyloid beta plaques in the brain. The manufacturer is required to conduct an additional randomized controlled trial to establish that reducing amyloid beta plaques with aducanumab improves clinical outcomes in patients with Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

View the Comparison Table: Drugs for Alzheimer's Disease

The FDA has approved Namzaric (Forest), a fixed-dose combination of extended-release (ER) memantine (Namenda XR), an NMDA-receptor antagonist, and donepezil (Aricept, and generics), an acetylcholinesterase inhibitor, for treatment of moderate to severe Alzheimer's type dementia in patients previously stabilized on both drugs. The patent for Namenda has recently expired and generic formulations of memantine 5- and 10-mg tablets have been approved.

Alzheimer's disease (AD) is the most common cause of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, and vascular dementia. Mild cognitive impairment (MCI) is generally defined as cognitive decline greater than expected for an individual's age and educational level, but not interfering with activities of daily living; it may be a transitional state between the cognitive changes of normal aging and dementia.

The FDA has approved florbetapir F18 (flor bay´ ta pir; Amyvid – Lilly), an intravenous radioactive diagnostic agent used with positron emission tomography (PET) scans, to estimate β-amyloid neuritic plaque density in adults being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.

The FDA has approved Nuedexta (Avanir), a fixed-dose combination of the cough suppressant dextromethorphan hydrobromide and the antiarrhythmic quinidine sulfate, for oral treatment of pseudobulbar affect. The combination is the first treatment approved by the FDA for this indication. Studies to support the effectiveness of Nuedexta were performed in patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS); the drug has not been shown to be safe or effective in other types of emotional lability.

Chelation therapy involves oral administration, intravenous infusion or intramuscular injection of drugs that increase excretion of heavy metals. The Medical Letter’s last article on this subject found no evidence that it was effective for treatment of cardiovascular disease. Since then, off-label use of chelation therapy has expanded to include treating children with autism and adults with Alzheimer’s disease, cancer and other chronic diseases.

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Alzheimer’s disease (AD) is the most common form of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson’s disease, dementia with Lewy bodies or vascular dementia. Mild cognitive impairment (MCI) has been defined as cognitive decline greater than expected for an individual’s age and educational level, but not interfering with activities of daily living; it may be a transitional state between the cognitive changes of normal aging and dementia.

Cholinesterase inhibitors are now used routinely in patients with dementia. Rivastigmine transdermal system (Exelon Patch - Novartis), a patch formulation of the cholinesterase inhibitor rivastigmine tartrate, has been approved by the FDA for treatment of mild to moderate dementia associated with Alzheimer's or Parkinson's disease. An oral formulation of rivastigmine tartrate has been available in the US since 2000,2 but gastrointestinal adverse effects possibly related to rapidly rising serum concentrations have limited its use.

Alzheimer's disease (AD) is the most common form of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, or vascular dementia. Mild cognitive impairment (MCI) has been defined as cognitive decline greater than expected for an individual's age and educational level, but not interfering with activities of daily living; it may be a transitional state between the cognitive changes of normal aging and the earliest stages of dementia.1 In longitudinal studies, the rate of progression from MCI to clinically diagnosable AD is 10-15% per year.

Dehydroepiandrosterone (DHEA), an endogenous adrenal steroid, is marketed as a dietary supplement in the US. It is widely promoted to reverse the effects of aging (loss of muscle, memory and libido) and has been used by athletes as a substitute for anabolic steroids. DHEA is banned by the International Olympic Committee, National Collegiate Athletic Association, National Football League and other sports organizations, but it was specifically exempted from becoming a controlled substance in the Anabolic Steroid Control Act of 2004.

Solifenacin succinate (VESIcare - Yamanouchi and GlaxoSmithKline) and darifenacin hydrobromide (Enablex - Novartis) have been approved by the FDA for oral treatment of overactive bladder.

Memantine hydrochloride, which has been used to treat dementia in Germany (Axura Merz) since 1982, has become the latest word-of-mouth miracle drug for Alzheimer's disease in the US (G Kolata, NY Times, June 15, 2003). Forest Laboratories has submitted a New Drug Application to the FDA for memantine. This review describes the standard treatment for Alzheimer's Disease, mechanism of action, clinical studies, adverse effects and dosage. Also included are sections on availability of the drug and how some people are obtaining memantine from abroad.

Tacrine hydrochloride (Cognex - Parke-Davis), an acridinamine derivative, will soon be available for treatment of cognitive deficits associated with Alzheimer's disease.