Psychosis with continuous delivery of subcutaneous levodopa: importance of the correct patient profile

Continuous 24-h subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp), a soluble formulation of levodopa prodrugs delivered through a minimally invasive subcutaneous infusion system, is currently available for the management of advanced Parkinson’s disease (APD) in many countries. Pivotal licensing studies and open-label studies confirm the efficacy of this first subcutaneous 24-h levodopa delivery option in APD in terms of motor effects, early-morning off periods, and sleep benefits. However, in addition to reports of skin reactions, there are also case report series and case-based concerns regarding neuropsychiatric side effects such as psychosis and hallucinations in some centres. The pattern appears to be either an early or late occurrence of psychosis, often in older patients with significant comorbidities. A critical review of such reports shows that the selected cases might have been vulnerable to psychosis, and potential corrective adjustments to the dosing of LDp/CDp were not evident; in some cases, there were unusual initiation processes. We review the entire published literature on clinical case reports of psychosis and the use of LDp/CDp and provide expert opinion-based tips on correct patient profiling and selection and on avoiding discontinuation of LDp/CDp therapy.