Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial
ABSTRACT Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD.
We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score.
101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 (-25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group.
Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD.
Clinicaltrials.gov reference: NCT00767091.
- Journal of neurology, neurosurgery, and psychiatry 01/2014; 85(10). DOI:10.1136/jnnp-2013-307224 · 5.58 Impact Factor
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ABSTRACT: Cognitive impairment and dementia pose particular challenges in the management of patients with Parkinson's disease (PD). Decision-making capacity can render patients vulnerable in a way that requires careful ethical considerations by clinicians with respect to medical decision making, research participation, and public safety. Clinicians should discuss how future decisions will be made as early in the disease course as possible. Because of cognitive, visual, and motor impairments, PD may be associated with unsafe driving, leading to early driving cessation in many. DBS of the STN and, to a lesser degree, globus pallidus interna (GPi) has consistently been associated with decreased verbal fluency, but significant global cognitive decline is usually not observed in patients who undergo rigorous selection. There are some observations suggesting lesser cognitive decline in GPi DBS than STN DBS, but further research is required. Management of PD dementia (PDD) patients involves both pharmacological and nonpharmacological measures. Patients with PDD should be offered treatment with a cholinesterase inhibitor taking into account expected benefits and potential risks. Treatment with neuroleptics may be necessary to treat psychosis; classical neuroleptics, as well as risperidone and olanzapine, should be avoided. Quetiapine might be considered first-line treatment because it does not need special monitoring, although the strongest evidence for efficacy exists for clozapine. Evidence from randomized, controlled studies in the PDD population is lacking; selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors may be used to treat depressive features. Clonazepam or melatonin may be useful in the treatment of rapid eye movement behavior disorder. © 2014 International Parkinson and Movement Disorder SocietyMovement Disorders 04/2014; 29(5). DOI:10.1002/mds.25870 · 5.68 Impact Factor
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ABSTRACT: Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease.Current Opinion in Neurology 06/2014; DOI:10.1097/WCO.0000000000000118 · 5.73 Impact Factor