title: 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.
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, University College London, United Kingdom.
authors.forename: Regina
authors.initials: R
authors.lastname: Katzenschlager
authors.forename: Andrew
authors.initials: A
authors.lastname: Hughes
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Manson
authors.forename: Marion
authors.initials: M
authors.lastname: Hoffman
authors.forename: Lesley
authors.initials: L
authors.lastname: Swinn
authors.forename: Hilary
authors.initials: H
authors.lastname: Watt
authors.forename: Kailash
authors.initials: K
authors.lastname: Bhatia
authors.forename: Niall
authors.initials: N
authors.lastname: Quinn
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001058:Apomorphine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010147:Pain Measurement / Q000379:methods; D010300:Parkinson Disease / Q000150:complications*; D011446:Prospective Studies; D012647:Self-Assessment; D018709:Statistics, Nonparametric
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D001058:Apomorphine