Successful Use of Donepezil for the Treatment of Psychotic Symptoms in Patients With Parkinson's Disease

Abstract

The risk of psychosis among patients with Parkinson's disease (PD) is high, and the management of these patients remains a substantial problem for physicians. Atypical antipsychotics, despite their advantages over conventional antipsychotics, can cause different side effects and deterioration of PD. Several reports have suggested that donepezil can be helpful in the treatment of psychotic conditions in patients with dementia with Lewy bodies and Alzheimer's disease. This report presents the results of preliminary study of six patients (four women, two men; age range, 60-75 years) with PD (range of duration, 3-7 years) and dementia complicated by psychosis. All patients were treated with antiparkinsonian therapy, and donepezil was added to their regular treatment. The severity of the psychotic symptoms was assessed using the Scale for the Assessment of Positive Symptoms, and extrapyramidal symptoms were assessed using the Simpson-Angus Scale. With the addition of donepezil (as much as 10 mg/day) to their constant antiparkinsonian treatment, five patients had clinically significant (more than 53%) improvement on the assessment scale, and one patient had minimal (24%) improvement after 6 weeks of the treatment. None of the patients had side effects or deterioration of parkinsonian symptoms. The results suggest that donepezil may ameliorate psychotic symptoms in patients with PD, but this will need to be tested further in controlled, double-blind trials.

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

“…Donepezil has been shown to improve cognition for up to 52 weeks in longterm treatment of NCDLB patients, without increasing the risk of Parkinsonian features or other clinically significant safety events [76,77]. Donepezil has also been shown to reduce Lewy pathology cholinergic impairment including hallucinations and delusions and psychotic symptoms in PD patients, without apparent side effects or exacerbation of Parkinsonian symptoms [78][79]. Although an early study suggested that treatment of NCDLB with Donepezil was sometimes associated with an increase in Parkinsonian features, a Cochrane database systematic review of previous research using cholinergic agonists to treat PD & NCDLB found that Donepezil produced consistent reduction in neurocognitive symptoms without exacerbation of Parkinsonian features or other side effects [87,88].…”

“…Based on researchdemonstrating Donepezil's efficacy in treating cholinergic impairment in patients with PD and NCDLB, and its effectiveness in reducing constipation and increasing bowel motility in non geriatric patients [73][74][75][76][77][78][79][88][89][90]93,94]. Donepezil has been used specifically to treatconstipation in PD and NCDLB patients, with consequent significant reduction of the symptom of constipation, without exacerbation or instigation of other symptoms [39].…”

A New Perspective in the Treatment of Parkinson’s Disease Psychosis

“…Cholinesterase inhibitors, including donepezil [53][54][55] and rivastigmine, 56 have been shown to improve symptoms of PDP in case reports and small openlabel studies; however, larger controlled studies are necessary to determine if these agents may be beneficial for PDP. A case report has suggested a potential benefit of mirtazapine for PDP; 57 however, antidepressants have been shown to induce or exacerbate psychotic symptoms, [58][59] so further research is necessary to determine if this is a reasonable treatment option for PDP.…”

Parkinson Disease Psychosis: Update

“…Since the clinical manifestations of DLB and PDP seem very close, if not identical, other than the obvious difference that many of the PDP patients are not demented, it would seem reasonable that they may also be helpful in PDP. The effects of CEI in PDP have been the subject of only a few open label trials [105][106][107][108][109], showing good tolerance and some benefit. One problem with such an approach is the long lag time between drug initiation and clinical response.…”