Abstract
Levodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson’s disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia. Clinical, demographic, dyskinesia rating scales were evaluated. Daytime dyskinesia was reduced in 75% (9/12) patients following treatment with 24-h therapy, including 7 who were compared with 16-h therapy and 2 that were transitioned from oral dopaminergic therapy to 24-h LCIG. Combining the data from all 12 subjects, troublesome dyskinesias were reduced during 24-h LCIG; UPDRS 4.1 (time spent with dyskinesias) mean change was −1.5 ± 0.75, p = 0.010 (Wilcoxon signed-rank test) and UPDRS 4.2 (functional impact of dyskinesias) mean change was −1.7 ± 0.90, p = 0.016, without changing their UPDRS part 3 “ON” scores (p = 0.138) or H&Y (p = 0.157). In 5 patients, improvement in dyskinesia occurred despite an overall increase in the total daily levodopa dose. None of the patients had worsening of dyskinesia after a median follow-up of 28 months. 24-h per day infusion of LCIG may be a useful strategy in the management of troublesome dyskinesias in PD patients with disabling dyskinesias resistant to attempts to optimise 16-hours per day therapy. We postulate that this may be due to a pharmacodynamic as opposed to pharmacokinetic mechanism.
Highlights
Evidence derived from randomised and open-label clinical studies support that levodopa-carbidopa intestinal gel (LCIG) 16-h infusion is efficacious in the treatment of levodopa induced dyskinesias (LID) despite an overall increase in mean daily levodopa dose, a benefit thought to be related to a change in levodopa pharmacokinetics with continuous drug delivery.[6,7]
The study was a retrospective analysis of all patients on 24-h LCIG therapy for whom pre-24-h and post-24-h UPDRS part 4.1 and 4.2 scores were available for analysis
Of the 12 patients whose data were available for analysis, the indications for 24-h LCIG treatment were as follows: troublesome dyskinesias alone unresponsive to 16-h therapy (n = 4); troublesome dyskinesias and levodopa-unresponsive freezing of gait (n = 2), levodopa-unresponsive freezing of gait with nontroublesome dyskinesias (n = 3) or troublesome dyskinesia and nocturnal akinesia (n = 2), self-initiated (n = 1, index patient)
Summary
Evidence derived from randomised and open-label clinical studies support that LCIG 16-h infusion is efficacious in the treatment of levodopa induced dyskinesias (LID) despite an overall increase in mean daily levodopa dose, a benefit thought to be related to a change in levodopa pharmacokinetics with continuous drug delivery.[6,7] The pathophysiology of LID is complex,[8] and treatment of these disabling complications currently represents an unmet need in the treatment of patients with PD. Current treatment options for LID include amantadine, 24-h apomorphine infusion and deep brain stimulation, these therapies are not uniformly available or suitable for all patients. We describe the experience of our movement disorder unit in the use of 24-h LCIG infusion in the treatment of dyskinesias
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