End-of-dose motor fluctuations are regarded as one of the core troublesome symptoms by patients with Parkinson’s disease (PD). Treatment of levodopa (l-dopa)-induced motor fluctuations is still an unmet medical need. l-dopa is the gold standard in the treatment of motor PD symptoms; notwithstanding, a wide range of adjunct therapies are currently available for the treatment of end-of-dose motor fluctuations. Additionally, device-aided therapies, such as deep brain stimulation, l-dopa-carbidopa intestinal gel infusion, and on-demand injection or continuous apomorphine infusion, may be considered when oral treatments are not sufficient to control motor fluctuations. In spite of the several evidence-based reviews and guidelines available, there is no agreement on which add-on therapy should be started first or its optimal timing. Equally challenging is the choice and timing between device-aided therapies. Herein, we propose a general overview of oral and device-aided treatments for PD patients with end-of-dose motor fluctuations, offering two possible algorithms that can guide clinicians during the therapeutic decision process.
