LONDON, UK – For years, common treatments — levodopa and dopamine agonists (dopamine replacement therapy [DRT]) – have been implicated in Parkinson’s disease psychosis. A report published in Movement Disorder Clinical Practice pointed out that the relationship between DRT and neurotransmitter dysfunction inherent to PD remains unclear, however.1

A study team led by researchers from Kings College London and including the Parkinson’s Disease and Mental Illness Research Education and Clinical Centers at the Philadelphia VAMC sought to, examine the relationship between baseline striatal dopamine transporter (DAT) binding in drug-naïve idiopathic PD, introduction of DRT, or dose change and incident early-onset Parkinson’s disease psychosis.

For the study, baseline DAT binding was compared between patients with and without incident psychosis, which was defined as hallucinations or delusions. The researchers controlled for age, sex, baseline cognition, and prospective DRT in the Parkinson’s Progression Markers Initiative cohort, and incident illusions were not considered psychosis symptoms.

Results indicated that, of 386 patients, 30 (8%) developed PDP (predominantly hallucinations, mean onset 42 months) and 355 (92%) had either no PDP symptoms (mean follow-up 64 months) or reported illusions only (111/355, 31%).

The authors noted that incident PDP was associated with reduced baseline striatal DAT binding, controlling for confounders (F 1,377 = 10.9; P = 0.001), but not with a specific DRT regime.

At the same time, six patients developed PDP when DRT free.

“There was no suggestion that PDP onset was coincident with starting levodopa or levodopa dose increase,” according to researchers, who added, “Incident illusions were not associated with reduced DAT binding.”

While the study said the interactions are not yet completely understood for dopamine mechanisms, medication, and other neurotransmitter systems implicated in PDP, “The findings highlight the role of disease-related dopamine mechanisms in the pathophysiology of hallucinations in Parkinson’s disease alongside medication.”


  1. Dave S, Weintraub D, Aarsland D, Ffytche DH. Drug and Disease Effects in Parkinson’s Psychosis: Revisiting the Role of Dopamine. Mov Disord Clin Pract. 2019;7(1):32–36. Published 2019 Nov 11. doi:10.1002/mdc3.12851