title: Motor and nonmotor complications in Parkinson's disease: an argument for continuous drug delivery?
abstract: The complications of long-term levodopa therapy for Parkinson's disease (PD) include motor fluctuations, dyskinesias, and also nonmotor fluctuations-at least equally common, but less well appreciated-in autonomic, cognitive/psychiatric, and sensory symptoms. In seeking the pathophysiologic mechanisms, the leading hypothesis is that in the parkinsonian brain, intermittent, nonphysiological stimulation of striatal dopamine receptors destabilizes an already unstable system. Accordingly, a major goal of PD treatment in recent years has been the attainment of continuous dopaminergic stimulation (CDS)-or, less theoretically (and more clinically verifiable), continuous drug delivery (CDD). Improvements in the steadiness of the plasma profiles of various dopaminergic therapies may be a signal of progress. However, improvements in plasma profile do not necessarily translate into CDS, or even into CDD to the brain. Still, it is reassuring that clinical studies of approaches to CDD have generally been positive. Head-to-head comparative trials have often failed to uncover evidence favoring such approaches over an intermittent therapy. Nevertheless, the findings among recipients of subcutaneous apomorphine infusion or intrajejunal levodopa/carbidopa intestinal gel suggest that nonmotor PD symptoms or complications may improve in tandem with motor improvement. In vivo receptor binding studies may help to determine the degree of CDS that a dopaminergic therapy can confer. This may be a necessary first step toward establishing whether CDS is, in fact, an important determinant of clinical efficacy. Certainly, the complexities of optimal PD management, and the rationale for an underlying strategy such as CDS or CDD, have not yet been thoroughly elucidated.
authors: National Parkinson Foundation Centre of Excellence and National RLS, King's College Hospital, 9th Floor Ruskin Wing, Denmark Hill, London, SE5 9RS, UK. ray.chaudhuri@nhs.net
authors: K Ray
authors: KR
authors: Chaudhuri
authors: Alexandra
authors: A
authors: Rizos
authors: Kapil D
authors: KD
authors: Sethi
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D009069:Movement Disorders / Q000188:drug therapy; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D015259:Dopamine Agents