Parkinson's disease (PD) is a chronic, progressive condition affecting around 1% of the population older than 60 years. Upon long-term treatment with
levodopa, the mainstay of treatment in PD, most patients, especially younger ones exposed to higher doses, will experience symptoms related to end-of-dose deterioration, peak-dose
dyskinesias, and other motor fluctuations. Therapeutic strategies are grounded on modification of oral
levodopa pharmacokinetics to extend
levodopa benefit and development of new routes of
drug delivery (e.g.,
levodopa/
carbidopa intestinal gel infusion) or long-acting formulations of existing
dopaminergic drugs to prolong the duration of striatal
dopamine receptors stimulation. As our understanding of the pathophysiology of motor complications evolves, our therapeutic armamentarium is actively expanding and the focus of research is now actively pointing to the new non-
dopaminergic agents acting both within the basal ganglia and in other brain regions (e.g., drugs acting on
glutamate,
GABA,
serotonin, and
calcium channels). Despite the fact that trials comparing the different therapeutic strategies are lacking, we aimed at devising practical evidence- and experience-guided suggestions for the clinical management of motor complications, emphasizing that this should always be an individualized endeavor. This review summarizes the pharmacological management of motor complications in PD, including new formulations and routes of delivery, and the newer released drugs such as
istradefylline,
opicapone,
safinamide, and
zonisamide. Advanced therapeutic strategies for selected cases such as treatment with
apomorphine and surgical techniques (
deep brain stimulation) are also discussed. A comprehensive knowledge of the available options and evidence is fundamental for the successful management of these challenging complications.