Management of Psychosis in Parkinson's Disease

Psychosis in Parkinson’s disease represents a prevalent and distressing non-motor complication characterised by visual hallucinations, illusions and delusional beliefs. Its pathogenesis is multifactorial, encompassing dopaminergic therapy effects, serotonergic and cholinergic dysregulation, and underlying neurodegenerative changes. Management demands a careful balance between alleviating psychotic symptoms and preserving motor function. Non-pharmacological strategies include environmental optimisation, structured routines and caregiver education to reduce sensory overload and anxiety. Pharmacotherapy principally relies on antipsychotic agents with minimal dopaminergic antagonism. Clozapine remains the gold-standard in refractory cases, given its efficacy at low doses but constrained by haematological monitoring burdens. Pimavanserin, a selective serotonin 5-HT₂A receptor inverse agonist, has emerged as a targeted alternative that mitigates psychosis without exacerbating motor impairment. Other off-label atypical antipsychotics, such as quetiapine, are used for their favourable tolerability, albeit with mixed efficacy. Recent efforts focus on novel serotonergic inverse agonists, optimisation of drug delivery to reduce systemic exposure, and individualised de-escalation of dopaminomimetics. Integrated care pathways emphasise early detection, systematic assessment of risk factors for falls and cognitive decline, and coordinated multidisciplinary input to improve quality of life and reduce institutionalisation.

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Management of Psychosis in Parkinson's Disease publication trend

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Technical terms

Parkinson’s disease psychosis: Psychotic symptoms arising in the context of Parkinson’s disease, including hallucinations and delusions.

Atypical antipsychotic: Second-generation antipsychotic agent with lower propensity for motor side effects due to reduced D₂ receptor blockade.

5-HT₂A receptor inverse agonist: Compound that binds to serotonin 2A receptors and decreases their basal activity below resting levels.

Pharmacokinetics: Study of the absorption, distribution, metabolism and excretion of a drug.

Dopaminergic therapy: Treatment strategies that augment dopamine signalling, commonly using levodopa or dopamine agonists.

References

1. Phase I clinical trial of NH130 and the prediction of its pharmacokinetics using physiologically based pharmacokinetic modeling. Frontiers in Pharmacology (2024).
2. Metabolism, Disposition, Excretion, and Potential Transporter Inhibition of 7–16, an Improving 5-HT2A Receptor Antagonist and Inverse Agonist for Parkinson’s Disease. Molecules (2024).
3. Treatment of Parkinson’s Disease Psychosis—A Systematic Review and Multi-Methods Approach. Biomedicines (2024).