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Family Practice News

If you’re stumped about which cholinesterase inhibitor to prescribe for your patients with newly diagnosed Alzheimer’s disease, rest assured that the clinical effects are similar with all such agents.

"There is no substantive scientific evidence that says one of the cholinesterase inhibitors is better than another, so get comfortable with one or two of them," Dr. Jeffrey L. Cummings advised during a psychopharmacology conference sponsored by the Nevada Psychiatric Association. "The effect is demonstrable late in the disease, so if you take patients with Mini-Mental State Exam scores of less than 10, you still get the same response that you do in somebody whose Mini-Mental State Exam score is 20. There’s no proven effect on the underlying disease state."

Clinical evidence from nearly 20 years of cholinesterase inhibitor use suggests that 25% of patients who take them will experience modest cognitive improvements, defined as a 2-4 point increase on the Alzheimer’s Disease Assessment Scale-cognitive subscale or a 1-2 point increase on the Mini-Mental State Exam. This "makes it very difficult to see a response if it’s not on the upper end of that [response]," Dr. Cummings said. "But about 80% of patients on cholinesterase inhibitors have a delay in decline of 6-9 months. That’s worthwhile, because patients are usually only on therapy for about 5 or 6 years over the course of their disease. So if you can delay almost 20% of that, that’s fantastic."

Dr. Cummings, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health, lets convenience drive the choice of which cholinesterase inhibitor to prescribe. "I sit with the patient and the caregiver and I ask: ‘Do you want a pill or a transdermal patch?’ If they say, ‘I want a pill,’ I give them donepezil. If they say, ‘I want a patch,’ I give them the rivastigmine transdermal patch," he said.

"I’m trying to respond to the perceived convenience of the caregiver. That’s the question I pose, and those are the two drugs I use."

He went on to note that donepezil "is more likely to give you diarrhea than rivastigmine is, and the rivastigmine patch will give you a rash in 5-10% of patients. Bradycardia is a contraindication for all cholinesterase inhibitors."

Donepezil is available in 5-mg, 10-mg, and 23-mg formulations. The 23-mg form is approved only for patients with moderate to severe disease. "There is more diarrhea with the 23-mg dose; maybe 15% of patients will get diarrhea with that higher dose," he said. "To ameliorate this, for 1 month I have patients go from 10 mg to 15 mg before jumping to the 23-mg dose. I think that helps rather than going directly from 10 mg to 23 mg."

Rivastigmine is approved for mild to moderate Alzheimer’s and for patients with mild to moderate Parkinson’s disease dementia. It’s available in 1.5-mg, 3-mg, 4.5-mg, and 6-mg capsules, or as a 4.6-mg or 9.5-mg transdermal patch.

Galantamine is another cholinesterase inhibitor approved for patients with mild to moderate Alzheimer’s disease, and it has dosing options of 6 mg, 8 mg, or 12 mg b.i.d. Extended formulations are available in 12-mg and 24-mg doses.