The Effects of Rivastigmine on Neuropsychiatric Symptoms in the Early Stages of Parkinson's Disease: A Systematic Review.

BACKGROUND AND PURPOSE:Neuropsychiatric symptoms including depression, apathy and psychosis occur frequently in patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia, but whether the use of rivastigmine is effective earlier in the disease course is unclear. The aim of this systematic review was to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia. METHODS:Embase, Medline, PsychINFO, Cochrane CENTRAL, NGLC, National Institute for Health and Care Excellence Evidence and medRxiv.org were searched for studies with terms relating to population (Parkinson's disease) and intervention (rivastigmine). Of 1922 references identified, 358 were duplications. Following title and abstract review, 1331 articles were excluded. After full-text review, nine articles remained. RESULTS:Outcomes were heterogenous, therefore, the results are presented in narrative form. The articles included six randomized controlled trials, two open-label trials and one case series. Outcome measures included: time to develop psychosis; frequency of rapid eye movement sleep behaviour disorder (RBD) episodes; apathy; gait variability; falls; cognitive ability; Neuropsychiatric Inventory score; and regional spontaneous brain activity. CONCLUSIONS:There is evidence that rivastigmine is beneficial for RBD and apathy in Parkinson's disease patients without dementia. There is high level evidence that rivastigmine reduces falls, which may be due to improved attention. The impact of rivastigmine on psychotic symptoms is less clear, but is supported by current theoretical models which involve acetylcholine dysfunction in the generation of visual hallucinations in Parkinson's disease.