Non-oral Continuous Drug Delivery Techniques in Parkinson's Disease: For Whom, When, and How?

Continuous dopaminergic stimulation (CDS) has become one of the main concepts in present Parkinson's disease (PD) research. This is based on the assumption that CDS, or rather near CDS, is the normal striatal setting in a healthy individual. In PD, the degeneration of dopaminergic neurons leads to a reduced capacity to buffer dopamine, which could increase the vulnerability to a pulsatile administration of drugs. The term continuous drug delivery (CDD) describes the process of delivering drugs continuously with the aim of achieving CDS. There are three principal techniques for non-oral CDD: continuous subcutaneous apomorphine infusion CSAi), levodopa-carbidopa intestinal gel infusion (LCIGi), and transdermal rotigotine therapy. CDD has repeatedly been shown effective in the day-to-day treatment of PD patients. Although this review does not replace local guidelines regarding the use of the included non-oral CDD-based therapies, we have compiled the current base of evidence or consensus view with the intention of facilitating both the selection and the use in a clinical setting. The indications for CSAi and LCIGi are very similar and are centered around motor complications in advanced PD, whereas rotigotine has been proven effective both as a monotherapy in early PD and as an add-on to levodopa in advanced PD. Deep-brain stimulation is a relevant option for many of the patients with advanced PD, and we therefore also discuss its use in relation to the CDD-based techniques. Blinded and controlled trials have shown that non-oral CDD is an effective approach for the treatment of PD.