Moving from continuous dopaminergic stimulation to continuous drug delivery in the treatment of Parkinson's disease

Motor fluctuations and motor complications are a major consequence of the treatment and progression of Parkinson's disease (PD) and they have, in particular, been linked to L-dopa therapy. Using continuous dopaminergic stimulation (CDS) by employing longer acting dopaminergic drugs has been proposed as a means of avoiding or lowering their occurrence. However, both the preclinical and clinical evidence base suggest that this concept does not fully explain the differences between L-dopa and dopamine (DA) agonist drugs and that their pharmacological profiles may also be important. In addition, the way in which drugs are delivered in PD appears to have a marked influence on both efficacy and side-effect profile. As a consequence, the concept of continuous drug delivery (CDD) has arisen to explain the differences between the intermittent and continuous delivery of both L-dopa and DA agonists. This review presents the evidence for using CDD as a working concept for the early and later stages of PD and in the treatment of motor complications and motor fluctuations. CDD as an approach to the treatment of PD may improve the outcome of therapy and explain the differences between drug classes and the delivery systems employed.