Evolution of strategies for selecting dopaminergic therapy in Parkinson’s disease

Over the past five decades, strategies for dopaminergic therapy in Parkinson’s disease (PD) have evolved significantly. Historically treatments aimed to reduce parkinsonism symptoms. Later, the focus shifted to preventing motor fluctuations and dyskinesias, leading clinicians to delay levodopa initiation. As knowledge of the mechanisms underlying motor complications, the clinical relevance of non-motor symptoms, and the efficacy and safety profiles of various dopaminergic drug classes increased, clinicians developed a personalized approach to therapy selection. This article reviews the scientific concepts that informed current approaches to dopaminergic therapy in PD. It evaluates clinical studies comparing levodopa and dopamine receptor agonists as initial therapies, the rationale for revising the strategy of delaying levodopa initiation, and current principles for treatment selection at different disease stages. The analysis addresses patient age and age at PD onset, severity of motor and non-motor symptoms, risk factors for motor fluctuations and dyskinesias, cognitive and psychiatric status, and individual susceptibility to adverse effects from dopaminergic therapy. The article also examines the benefits and limitations of different dopaminergic drug classes. The findings suggest that current strategies prioritize personalized and rational use of dopaminergic agents at various stages of PD, tailored to the patient’s clinical profile.