TY - JOUR
T1 - Motor and nonmotor complications in Parkinson's disease
T2 - An argument for continuous drug delivery?
AU - Chaudhuri, K. Ray
AU - Rizos, Alexandra
AU - Sethi, Kapil D.
N1 - Funding Information:
The authors would like to thank Michael Feirtag for his editorial assistance in the preparation of this manuscript and The Curry Rockefeller Group, LLC, Tarrytown, NY, for providing editorial support. Funding for this support was provided by Abbott. Abbott provided a medical accuracy review of the final manuscript but had no input on the development of the manuscript or presentation of the content. The authors are solely responsible for the content of the manuscript and also had final responsibility for the decision to submit for publication.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Continuous drug delivery
KW - Motor complications
KW - Nonmotor fluctuations
KW - Parkinson's disease
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U2 - 10.1007/s00702-013-0981-5
DO - 10.1007/s00702-013-0981-5
M3 - Article
C2 - 23456290
AN - SCOPUS:84883455518
SN - 0300-9564
VL - 120
SP - 1305
EP - 1320
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 9
ER -