Unexpected Findings During Double-blind Discontinuation of Acetylcholinesterase Inhibitor Medications

Abstract Purpose The long-term effects of acetylcholinesterase inhibitors (AChEIs) used in the treatment of patients with various types of dementia remain unclear, largely due to challenges in the study of their discontinuation. We present several unexpected results from a discontinuation trial that might merit further investigation. Methods This double-blind, placebo-controlled study of the discontinuation of AChEI medications was conducted in 62 US veterans. Participants were randomized to receive continued treatment with their medication (sham-taper group) or to treatment discontinuation via tapering (real-taper group), over a period of 6 weeks. The primary end point was the patient's/family caregiver's decision to discontinue the study medication. Findings The study was underpowered to detect a significant between-group difference in the primary end point, but examination of the discontinuation process generated several unexpected results: (1) recruitment proved extremely challenging for a variety of reasons, with Implications These findings argue for the use of caution in discontinuing AChEIs in patients with Parkinson disease–associated dementia, although there may be potential benefits of a "drug holiday." The findings also urge the consideration of distress on the part of the caregiver while making medication treatment decisions in dementia. Future research must address challenges with recruitment and symptom fluctuations.