Donepezil for Lewy Body Constipation: A Six-Month Follow-up

Abstract

In a previous case study, four patients at different stages of Parkinson's disease (PD) and Neurocognitive Disorder with Lewy Bodies (NCDLB) disease progression were treated with Donepezil, with the intention of mitigating Lewy body impairment of the cholinergic pathways in the myenteric plexus, increasing bowel motility, and reducing the symptom of constipation. In all four cases, the use of Donepezil was associated with significant reduction of the symptom of constipation. There was no exacerbation or instigation of other symptoms. The symptom status of the four patients was reviewed six months later. In none of the patients has there been exacerbation of the symptom of constipation, nor emergence of new symptoms. The findings suggest that Donepezil might have long-term efficacy for reducing constipation in patients with PD and NCDLB. Further research is recommended using larger numbers of subjects matched for diagnosis, age, gender, and other variables.

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

“…A follow up study indicated that the progression of Lewy body pathology had advanced in some patients, leading to exacerbation of CNS and ANS symptoms including blunted affect, dysphoric mood, generalized anxiety, sleep disturbance (onset, median and terminal waking, REM sleep behavior disorder or RSBD and/or REM sleep without atonia, or RSWA), cognitive interference (short-term memory loss and difficulty with wordfinding), passive suicidal ideation, appetite suppression, and exacerbation of Parkinsonian features (motor retardation, joint and muscle pain, reduced range of motion, diminished strength and coordination, increased tremor, gait disturbances, and difficulties with balance). However, there was no exacerbation of the symptom of constipation, nor emergence of new symptoms in any of the patients in the study, suggesting that Donepezil might have long-term benefit for mitigating cholinergic Lewy pathology in the ENS of patients with PD and NCDLB [40].…”

“…Donepezil has demonstrated efficacy in mitigating Lewy body impairment of the cholinergic pathways in the MP and CSMP of patients diagnosed with PD and NCDLB, increasing bowel motility and reducing the symptom of constipation, without exacerbating or instigating other symptoms [39,40]. One possible conclusion is that the use of the AChEI Donepezil compensates at least in part for Lewy body impairment of cholinergic pathways in the MP and CSMP, reducing the symptom of constipation in patients with PD and NCDLB.…”

“…Lewy body cholinergic impairment in the ENS manifests symptomatically as gastric immotility and constipation [13,[31][32][33][34][35][36][37][38][39][40][41]. Increased colonic transit time and impaired gastric emptying are frequently found in PD patients [35,42].…”

“…LPD and NCDLB patients with significant Parkinsonian motoric/gait features are often prescribed L-dopa agents like Carbidopa-Levodopa (known also by the brand names Sinemet and Stalevo) in order to preserve gait, balance, and other basic motor functions [40,57,58]. Carbidopa-Levodopa's potential side effects include constipation [59].…”

“…Donepezil's dual action has made it a longstanding choice for countering cholinergic impairment [74,95,98]. Donepezil's successful employment in the treatment of constipation in case studies of patients with PD and NCDLB, as well as its demonstrated efficacy in reducing constipation in PD and NCDLB patients using Carbidopa-Levodopa, suggests that the mechanism of boostingACh levels in the MP and CSMP restores motility to the bowel, significantly reducing constipation without increasing Parkinsonian features or other clinically significant symptoms [39,40].…”