Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: A prospective study using single‐dose challenges

Abstract

Continuous subcutaneous (SC) infusion of the dopamine agonist apomorphine was shown in retrospective studies to improve drug-induced dyskinesias in Parkinson's disease (PD). We prospectively assessed the antidyskinetic effect of continuous SC apomorphine therapy using subjective and objective measures, and sought to determine whether any observed dyskinesia reduction could be corroborated using single-dose dopaminergic challenges. Twelve PD patients with on-off fluctuations and disabling dyskinesias who were scheduled to start apomorphine pump treatment underwent acute levodopa and apomorphine challenges at baseline and 6 months later. Video recordings involving motor tasks were rated blindly by two independent raters using modified AIMS and Goetz dyskinesia scales. At 6 months, mean apomorphine dose was 75.2 mg per day and the mean L-dopa dose had been reduced by 55%. Daily off time in patients' diaries was reduced by 38% (2.4 hours). The L-dopa challenges showed a reduction of 44% in AIMS and 40% in Goetz scores (both P < 0.01). Apomorphine challenges showed a reduction of 39% in AIMS and 36% in Goetz scores (both P < 0.01). Patients' self-assessment scores reflected these significant changes. Dyskinesia improvement correlated with reduction in oral medication and with the final apomorphine dose (P < 0.05). This prospective study confirms marked dyskinesia reduction on continuous subcutaneous apomorphine therapy, paralleled by reduced dyskinesias during dopaminergic challenge tests. Our findings support the concept that replacement of short-acting oral antiparkinsonian medication with continuous dopamine receptor stimulation may reverse, at least partially, the sensitization process believed to mediate the development of drug-induced dyskinesias in PD.

Levodopa in the treatment of Parkinson&rsquo;s disease: an old drug still going strong

“…[58][59][60] The same differences have also been observed in studies comparing pulsatile versus continuous delivery of the same dopaminergic agent. 61,62 Such results are consistent with clinical studies of continuous infusions of DAs, such as apomorphine 63,64 or lisuride, 65 which were found to downregulate pre-existing LD-induced dyskinesia. Indeed, when given as continuous intraduodenal infusions, marked reductions in dyskinesia have been reported for LD itself 49,53,66,67 and the gel preparation of LD (Duodopa ® , Solvay Pharmaceuticals GmbH).…”

Algorithms for the treatment of motor problems in Parkinson's disease

“…Long‐term data are sparse, and it appears that the dropout rate is often higher than for the other advanced therapies 68. However, also this method is safe and effective in patients with bothersome motor complications,69, 70, 71 reducing off‐time and improving dyskinesias. Skin complications at the infusion site are among the most common adverse reactions, as are dopamine agonist side effects like neuropsychiatric changes, somnolence and orthostatic hypotension.…”

Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

“…Apomorphine infusion has also been shown to improve drug-induced dyskinesias, allowing a reduction in the oral levodopa dose. 5 Nowadays, apomorphine is recognised by clinicians as an established therapy, backed by many patient-years of experience, which still has considerable value in helping to manage the complex problems they face in treating PD patients in their daily clinical practice.…”