What is the medication first used to treat Alzheimer's disease?

From the Guidelines

The first medication approved specifically for Alzheimer's disease was tacrine (brand name Cognex), which received FDA approval in 1993. Tacrine is an acetylcholinesterase inhibitor that works by preventing the breakdown of acetylcholine, a neurotransmitter important for memory and thinking. The typical starting dose was 10 mg four times daily, which could be gradually increased to a maximum of 40 mg four times daily, as stated in the guidelines for managing Alzheimer's disease 1. However, tacrine is no longer used in clinical practice due to its significant side effects, particularly liver toxicity that required frequent blood monitoring, and a challenging dosing schedule requiring four daily doses.

After tacrine, second-generation cholinesterase inhibitors like donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) were developed with better safety profiles and more convenient dosing schedules, as discussed in the effectiveness of cholinesterase inhibitors and memantine for treating dementia 1. These medications became the standard first-line treatments for Alzheimer's disease, though they primarily provide symptomatic relief rather than altering the underlying disease progression. Key points to consider when prescribing these medications include:

• Donepezil's initial dosage is 5 mg once daily, which can be increased to 10 mg once daily after 4 to 6 weeks, with mild side effects including nausea, vomiting, and diarrhea 1.
• Rivastigmine's initial dosage is 1.5 mg twice daily, which can be increased as tolerated but no more quickly than by 1.5 mg twice daily every 4 weeks to a maximum of 6 mg twice daily, with side effects including nausea, vomiting, diarrhea, headaches, and dizziness 1.
• Galantamine's initial dosage is 4 mg twice daily, which is then increased to 8 mg twice daily for at least 4 weeks, with mild side effects including nausea, vomiting, and diarrhea, and is contraindicated for use in patients with hepatic or renal impairment 1.

Given the potential side effects and the need for careful patient monitoring, tacrine is no longer considered a first-line treatment for Alzheimer's disease, and its use has been largely replaced by the second-generation cholinesterase inhibitors.

From the FDA Drug Label

The effectiveness of donepezil hydrochloride in the treatment of patients with moderate to severe Alzheimer’s disease was established in studies employing doses of 10 mg/day and 23 mg/day The effectiveness of donepezil hydrochloride as a treatment for severe Alzheimer's disease is demonstrated by the results of a randomized, double-blind, placebo-controlled clinical study conducted in Sweden (6 month study) in patients with probable or possible Alzheimer's disease diagnosed by NINCDS-ADRDA and DSM-IV criteria, MMSE: range of 1 to 10

The medication Donepezil was used to treat Alzheimer's disease.

• Donepezil is used for the treatment of moderate to severe Alzheimer’s disease.
• The effective doses of Donepezil for this treatment are 10 mg/day and 23 mg/day 2

From the Research

Medication for Alzheimer's Disease

• The first medication licensed for the symptomatic treatment of Alzheimer's disease was tacrine, a cholinesterase inhibitor 3, 4, 5, 6.
• Tacrine was initially widely marketed for the treatment of Alzheimer's disease, but its use was later restricted due to side effects such as hepatotoxicity and gastrointestinal problems 3, 4, 5.
• Despite its limited use, tacrine remains a significant drug in the history of Alzheimer's disease treatment, and its structure has been used as a basis for the design of new drugs with potentially fewer side effects 6.
• Current pharmacological treatment of Alzheimer's disease includes cholinergic replacement therapy, which has shown modest but significant benefits for people diagnosed with the disease 7.
• Researchers continue to explore new strategies for the treatment of Alzheimer's disease, including disease modification and primary prevention 7.

Key Findings

• Tacrine was the first drug approved by the FDA for the treatment of Alzheimer's disease 6.
• The efficacy of tacrine for symptoms of dementia remains controversial due to difficulties in interpreting clinical trial results 4, 5.
• Tacrine's use is associated with adverse events, including raised serum liver enzymes and gastrointestinal side effects 4, 5.