Cholinesterase Inhibitors

The Parkinson's-Reversing Breakthrough

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In multiple AD trials, cholinesterase inhibitors had mild-to-moderate benefits in both cognition and psychosis (101,102). Cholinesterase inhibitors are also effective for psychosis in DLB patients and are a potential alternative to the atypical antipsy-chotics for PD psychosis. An early open-label study with tacrine showed that five of seven demented PD patients had complete resolution of psychotic symptoms (103); however, the use of this drug has been limited because of hepatic toxicity.

Fabbrini et al. (104) administered donepezil (5 mg qhs) to eight nondemented PD patients with visual hallucinations, with or without delusions. At the end of two months, subjects had decreased PPRS scores with hallucinations and paranoid ideation, being the most responsive. However, two patients experienced clinically significant motor decline. Another small open-label study enrolled six patients with PD, dementia, and psychotic symptoms and treated them with 10 mg/d of donepezil (105). Five patients showed moderate-to-significant improvement in psychosis and one showed minimal improvement. None had worsening of motor symptoms. Finally, Kurita et al. (106) reported three PD patients who had improvement of visual hallucinations with 5 mg/d of donepezil without worsening of motor function, but one patient had treatment emergent delusions that resolved, after donepezil was discontinued. Only one placebo-controlled trial of donepezil has been reported for PD psychosis (107). This was a randomized, crossover trial in 22 subjects with PD and dementia. There was no difference in BPRS scores between patients on donepezil and patients on placebo; however, the trial excluded patients with severe psychosis.

Rivastigmine can also improve hallucinations in PD patients (108,109). In a 24-week, double-blind, placebo-controlled, randomized trial of 541 PD patients with dementia (110), patients on rivastigmine showed a mean improvement of 2.0 on the NPI, from a baseline mean score of 12.7.

There is one open-label study of galantamine on psychosis in PD (111). Seven of the nine patients in this study with hallucinations improved, three of whom had complete amelioration of psychosis. However, three patients experienced increased tremor.

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