End-of-dose deterioration in non ergolinic dopamine agonist monotherapy of Parkinson’s disease

Abstract

The study was designed to investigate the possible occurrence of "wearing-off" (WO) during dopamine agonist (DA) monotherapy. Sixty patients with "de novo" idiopathic PD were randomised into one of two DA monotherapy branches to receive oral ropinirole at 15 mg per day, or pramipexole at 2.1 mg per day. DA doses could be increased in the following two years but levodopa could not be added until the study ended. WO was assessed by self-evaluation charts confirmed by a blinded observation of a 30% or greater deterioration in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Proc Mixed and Kaplan-Meier curves evaluated treatment variables as a function of time. T-tests were used to compare post-hoc variables reclassified according to WO occurrence. Thirty patients received ropinirole, and 30 pramipexole monotherapy. Eighteen patients (30%) experienced "wearing-off" 15-21 months after beginning monotherapy. No differences were observed between treatments. WO phenomena was observed 3.4+/-0.3 hours after intake of the morning or afternoon dose and consisted of UPDRS score worsening by 11.1+/-2.1 points (69-111% more than "on" score). Statistical evaluation gave evidence of differences between patients who experienced WO and those who did not: UPDRS motor scores obtained at admission to the study were higher (by 3.4+/-0.2 points, p=0.01 t-test) and DA doses at 6-12 months were higher in fluctuating patients. UPDRS motor scores deteriorated, however. similarly and there were no differences, in UPDRS scores recorded in ON conditions, between fluctuating and non-fluctuating patients at the end of the study. Our findings provide evidence of WO phenomena in patients with early PD receiving non-ergolinic DA monotherapy.

The scientific and clinical basis for the treatment of Parkinson disease (2009)

“…Although less prominent, wearing-off has also been reported with dopamine agonists. 485 The particular treatment will depend on the severity of the wearing-off problem, whether it is complicated by dyskinesia, and on how dopaminergic therapy was initially started. Treatment options are similar to those for suboptimal motor response and include the following:…”

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

“…Indeed, wearing-off effects have also been reported with dopamine agonists that are not retained in the presynaptic compartment. 62 With disease progression there is a tendency for fluctuations to become increasingly less predictable and as the wearing-off phenomenon becomes more complicated, dosing responses vary and patients may report a 'delayed-on' effect or dose failures. The delayed-on effect refers to a significant delay between the intake of a dose of levodopa and the commencement of its effects.…”

Clinical neuroprotection in Parkinson's disease — Still waiting for the breakthrough

“…In a five year study comparing the incidence of dyskinesia in patients with early PD treated with the dopamine D2-receptor agonist ropinirole or levodopa, 66% of patients randomized to ropinirole treatment needed supplementary treatment with levodopa in order to adequately control symptoms [17]. This observation has been confirmed in a trial that studied the incidence of wearing-off in denovo PD patients subjected to monotherapy with the non-ergolinic dopamine agonists pramipexole and ropinirole [20]. In this study, 30% of patients experienced wearing-off 15-21 months after the onset of dopamine agonist monotherapy.…”