The Treatment of Older Patients with Parkinson's Disease

Abstract

Background: There are approximately 150 000 persons over age 80 in Germany who suffer from Parkinson's disease. Eighty percent of patients develop dementia during the course of this disease. Older patients with Parkinson's disease often suffer from the multimorbidity typically seen in this age group. Comorbidities affect the options for treating Parkinson's disease. Older patients are markedly underrepresented in most trials of antiparkinsonian drugs.

Methods: In this narrative review, we propose practical ways to simplify the treatment regimen of older patients with Parkinson's disease to lessen side effects and make treatment more manageable for these patients and the persons caring for them.

Results: The mainstay of treatment is levodopa in combination with a dopa decarboxylase inhibitor, taken during the day as a standardrelease or dispersible formulation and at night in extended-release form; along with a catechol-O-methyltransferase inhibitor if neces - sary. Antiparkinsonian drugs with other mechanisms of action should be used sparingly, if at all. Treatment options for patients with severe fluctuations in efficacy and long "off" (akinetic) phases include a jejunal levodopa pump and the subcutaneous administration of foslevodopa. Parkinson's disease dementia should be treated with rivastigmine, a cholinergic anti-dementia drug (approved in capsule form for this indication). Otherwise intractable psychosis should be treated with quetiapine (off-label) or clozapine (evidence-based; weekly blood tests required). Other neuroleptic drugs should not be given to patients with Parkinson's disease. Physiotherapy and speech therapy are evidencebased components of therapy with proven efficacy in every stage of the disease.

Conclusion: Further randomized controlled trials tailored to this patient population are needed to provide a better evidence base for the treatment of older patients with Parkinson's disease.

Figure

Effect/side effect ratio of various groups of anti-Parkinson’s medications This ratio is most favorable for levodopa, followed by catechol-O-methyltransferase inhibitors. We would like to thank Prof. Martin Wehling for his permission to modify the Figure depicted in his book (6).

eFigure

Plasma concentrations of levodopa and carbidopa (27) (licensed under CC BY-NC) (Othman AA et al., 2015) (mean value ± standard deviations) after oral administration of levodopa–carbidopa tablets (10 : 1 levodopa/carbidopa ratio; a, c) and intrajejunal infusion of levodopa–carbidopa intestinal gel (4 : 1 levodopa/carbidopa ratio after insertion of a PEJ tube; b, d) in Japanese patients with advanced Parkinson’s disease (n = 5). LCIG = levodopa-carbidopa intestinal gel In a long-term observational study involving 324 patients (duration 54 weeks, patient age 64.1 ± 9.1 years, disease duration 12.5 ± 5.5 years, median jejunal levodopa daily dose 1547 mg; 272 completed the trial), the most common side effects were complications associated with insertion of the jejunal tube. They mainly occurred shortly after insertion of the tube (34.9%). The daily off-time decreased by a mean of 4.4 h/65.6%, on-time without troublesome dyskinesia increased by 4.8 h/62.9%, the on-time with troublesome dyskinesia decreased by 0.4 h/22.5 % (e44). The advantages of levodopa administration via a jejunal tube in older patients are good symptom control and avoidance of levodopa peak levels. Pump treatment avoids the need for multiple single drug doses. Nursing staff can irrigate the pump and switch it on in the morning and switch it off in the evening. If necessary, the pump can continue to run during the night at a low dose. There is also the option of bolus administration as needed. Possible complications include dislocation or obstruction of the tube and inflammation around the insertion site. Patients with dementia and severe fine motor impairments are unable to operate the pump. Continuous levodopa administration is therefore reserved for patients who can operate the system themselves or who are very well cared for by relatives and/or nursing staff (e21).