A Parkinson’s treatment designed to smooth out the disease’s most disruptive motor fluctuations is now drawing attention to a different clinical challenge: psychotic complications that may emerge during therapy. A retrospective observational study of 198 patients has examined the real-world use of subcutaneous foslevodopa/foscarbidopa infusions, focusing on episodes involving hallucinations, delusions and other disturbances in the patient’s perception of reality. Published in npj Parkinson’s Disease, the report adds to a growing discussion about how advanced dopaminergic treatments can improve movement while potentially complicating cognition, behavior and psychiatric stability.
Parkinson’s disease is best known for tremor, slowed movement and muscle rigidity, but its biology extends far beyond the motor system. As dopamine-producing neurons degenerate, patients may also experience sleep disruption, depression, anxiety, impaired attention and cognitive decline. In advanced disease, oral medication can become increasingly difficult to manage because levodopa levels rise and fall rapidly. Patients may move well for a period and then suddenly become stiff or unable to walk as the drug effect fades. These “off” episodes can alternate with involuntary movements, creating a narrow therapeutic window in which clinicians must continuously balance mobility against adverse effects.
Foslevodopa/foscarbidopa is intended to address that instability through continuous delivery. Foslevodopa is a prodrug of levodopa, meaning it is converted in the body into the dopamine precursor that crosses the blood–brain barrier. Foscarbidopa serves as a prodrug of carbidopa, which inhibits the peripheral breakdown of levodopa before it reaches the brain. Delivered through a subcutaneous infusion system, the combination can provide a more consistent supply than multiple tablets taken throughout the day. The pharmacological aim is to reduce abrupt fluctuations in levodopa exposure and extend useful motor control in people whose symptoms are no longer adequately managed by conventional schedules.
The same dopaminergic system that supports movement is also deeply involved in motivation, reward, attention and the brain’s interpretation of sensory information. Increasing dopamine activity can therefore have effects that are not limited to the motor circuits affected by Parkinson’s disease. Psychosis in this setting may involve visual or auditory hallucinations, fixed false beliefs, suspiciousness or severe misinterpretation of ordinary events. Some patients recognize that an experience is unusual, while others may be convinced that it is real. Delirium, infection, sleep deprivation, dementia and other medications can produce similar symptoms, making clinical evaluation essential before a reaction is attributed to an infusion.
The new study, led by J.S. Siuda, J. Malkiewicz, M. Toś and colleagues, uses retrospective real-world data from 198 people treated with subcutaneous foslevodopa/foscarbidopa. Unlike a randomized clinical trial, a retrospective observational investigation looks back at medical records and treatment histories that were generated during routine care. This approach can reveal how a therapy behaves outside carefully selected trial populations, including patients with older age, multiple illnesses, cognitive vulnerability or complex medication regimens. It can also identify uncommon or clinically important complications that may not be fully visible in shorter controlled studies.
The central question is not simply whether psychosis can occur during treatment, but how clinicians should understand its timing, presentation and possible relationship to therapy. A psychotic episode may arise after a change in dopaminergic exposure, but it can also reflect the natural progression of Parkinson’s disease or a separate medical problem. Physicians typically consider recent medication adjustments, renal and metabolic health, infections, dehydration, sleep disturbance and pre-existing cognitive impairment. Other Parkinson’s medicines, including dopamine agonists and drugs used to treat motor symptoms, may contribute to hallucinations or delusions. In practice, identifying the responsible factor often requires reviewing the entire treatment plan rather than focusing on a single infusion.
The study’s real-world design is particularly relevant because continuous subcutaneous infusion is used by patients managing advanced disease in everyday settings, not only in specialist clinics. An infusion device can reduce the burden of repeated oral dosing, but it also introduces practical demands, including pump management, site care and monitoring for changes in symptoms. Any alteration in cognition or perception may affect a patient’s ability to operate the system safely or may place additional responsibilities on caregivers. Recognizing emerging psychosis early is therefore important not only for psychiatric well-being but also for medication adherence, fall prevention and the safe continuation of advanced therapy.
At the same time, the report should not be interpreted as proof that foslevodopa/foscarbidopa directly causes psychosis in every affected patient. Retrospective studies can identify patterns and associations, but they cannot control all the factors that influence why a treatment was started, why its dose was changed or why a patient developed hallucinations. The 198 participants may also represent the practices and patient population of particular treatment centers rather than every person receiving the therapy worldwide. The strength of such research lies in its clinical realism, while its limitations require cautious interpretation and, ideally, comparison with prospective registries and controlled studies.
For patients and families, the findings underline the importance of reporting new hallucinations, paranoia, confusion or abrupt behavioral changes rather than dismissing them as an unavoidable part of Parkinson’s disease. Clinicians may respond by searching for reversible triggers, adjusting dopaminergic medication, reviewing other drugs and evaluating cognition. In some cases, treatment for psychosis may be considered, but medication choices must be made carefully because several antipsychotic agents can worsen movement or sedation. The correct response is individualized: preserving mobility matters, but so do judgment, sleep, safety and the patient’s ability to distinguish internal experiences from external events.
As infusion-based therapies become more prominent in advanced Parkinson’s care, psychiatric monitoring is likely to become an increasingly important part of treatment design. The study of 198 real-world patients brings attention to a complication that can be overshadowed by the visible benefits of improved movement. Its broader message is that neurological treatment cannot be judged solely by walking speed, tremor reduction or time spent in an “on” state. The most successful therapy must also protect cognition, perception and independence. By examining psychotic complications in routine practice, the researchers provide a foundation for more precise risk assessment and for future guidance on delivering continuous dopaminergic therapy without losing sight of the brain’s wider vulnerability.
Subject of Research: Psychotic complications associated with subcutaneous foslevodopa/foscarbidopa infusions in patients with Parkinson’s disease.
Article Title: The psychotic complications of subcutaneous foslevodopa/foscarbidopa infusions – retrospective observational real-world data study including 198 patients.
Article References: Siuda, J.S., Malkiewicz, J., Toś, M. et al. “The psychotic complications of subcutaneous foslevodopa/foscarbidopa infusions – retrospective observational real-world data study including 198 patients.” npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01546-x
Image Credits: AI Generated
DOI: 10.1038/s41531-026-01546-x
Keywords: Parkinson’s disease, foslevodopa, foscarbidopa, subcutaneous infusion, psychosis, hallucinations, dopaminergic therapy, real-world study, neurological complications, advanced Parkinson’s treatment
Tags: advanced Parkinson’s medicationcognitive and behavioral effects of dopamine therapycontinuous drug delivery for Parkinson’sdopaminergic therapy side effectshallucinations and delusions in Parkinson’smanaging “off” episodes in Parkinson’smotor fluctuations managementParkinson’s disease treatmentpsychiatric stability in Parkinson’spsychotic complications in Parkinson’sreal-world Parkinson’s treatment studysubcutaneous foslevodopa/foscarbidopa infusions
