Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson's disease: current evidence and future perspectives

Introduction: Non-motor symptoms (NMS) affect patients with Parkinson's disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients' and caregivers' quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need. Areas covered: The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies. Expert opinion: The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer's disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers.