Idalopirdine Plus Cholinesterase Inhibitors Doesn’t Help Alzheimer’s Patients, Study Finds

Idalopirdine Plus Cholinesterase Inhibitors Doesn’t Help Alzheimer’s Patients, Study Finds
Three Phase 3 clinical studies have failed to reproduce previously reported benefits of adding investigational idalopirdine to a background therapy of cholinesterase inhibitors. The three randomized trials detected no improvements in cognition among mild to moderate Alzheimer's disease patients treated this way. The study, “Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease,” appeared in JAMA. To date, the U.S. Food and Drug Administration (FDA) has approved only two classes of medications for Alzheimer's: cholinesterase inhibitors such as Aricept (donepezil), Exelon (rivastigmine) and Razadyne (galantamine), and the NMDA receptor antagonist Namenda (memantine). The brains of Alzheimer's patients have lower levels of a neurotransmitter called acetylcholine. Cholinesterase inhibitors prevent an enzyme, called acetylcholinesterase, from breaking down acetylcholine. That increases acetylcholine levels and maintains communications between nerve cells. Patients with advanced Alzheimer’s may require higher doses of cholinesterase inhibitors, but this causes side effects such as nausea, vomiting and diarrhea. This means researchers must find ways of increasing acetylcholine without unwanted consequences. Previous Phase 2 studies suggested that idalopirdine — an antagonist of the serotonin 6 (5-HT6) receptor — added to cholinesterase inhibitor therapy could improve cognition in Alzheimer’s patients. In one of these studies, 90 mg/d of idalopirdine added to a stable dose of donepezil boosted
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