Published online by Cambridge University Press: 19 January 2024
In 1993, the first acetylcholinesterase inhibitor (AChEI), tacrine, was approved by the FDA for treatment of dementia. This class of medication is thought to work by raising levels of acetylcholine, an important neurotransmitter in the brain. There was a lot of excitement about the approval of tacrine, but almost immediately severe side effects including serious liver damage were encountered, and the use of the drug dwindled and disappeared almost overnight. I don’t think I ever wrote a prescription for tacrine. Three years later the first relatively safe AChEI, donepezil (trade name Aricept), was approved and it is still going strong. Within a few years, two similar drugs, rivastigmine and galantamine, were approved. They were all about equally effective. They all had similar side effects, but sometimes a person could tolerate one better than another. For an individual patient, it was hard to tell for sure if they were effective or not. A few of my patients had remarkable improvement and others didn’t seem to change much at all. For others, the side effects were intolerable. Most common were nausea, cramps, and diarrhea as well as nightmares and insomnia. I found that starting my patients at a very low dose, lower than recommended, and very slowly increasing the dose over several months would usually avoid the side effects.
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