¹Paracelsus Medizinische Universität, Salzburg, Austria
²Department of Neurology, Christian Doppler University Hospital, Centre for Cognitive Neuroscience, Member of the European Reference Network EpiCARE, Paracelsus Medical University of Salzburg, Salzburg, Austria
³Department of Geriatric Medicine, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
⁴Institute of Pharmacy, Pharmaceutical Biology and Clinical Pharmacy, Paracelsus Medical University, Salzburg, Austria

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Background: Psychosis is a common and debilitating non-motor complication in Parkinson’s disease (PD) that significantly impairs quality of life for patients and caregivers. Clozapine has demonstrated efficacy in treating Parkinson’s disease psychosis (PDP), effectively reducing hallucinations and delusions without worsening motor symptoms. However, its use is limited by the need for regular hematological monitoring due to the risk of agranulocytosis. Contrastingly, quetiapine is widely prescribed as a more convenient alternative, despite inconsistent and limited evidence for its efficacy in PDP. This divergence raises questions about real-world treatment experiences and prescribing practices.

Materials and Methods: This mixed-methods study integrated semi-structured interviews with patients hospitalized for PDP at a university center and a structured survey of neurologists and geriatricians involved in their care. Patient interviews explored perceptions of treatment effectiveness, adverse effects, quality of life, and autonomy. Physician surveys assessed prescribing preferences, attitudes towards clozapine monitoring burden, and perceptions of treatment challenges. The data were analyzed thematically and quantitatively to compare patient experiences with clinical practice.

Results: Eleven patients (mean age 81 years; 9 on quetiapine, 2 on clozapine) reported markedly different treatment experiences. Most patients treated with quetiapine described persistent hallucinations, sedation, dizziness, increased fall risk, and reduced independence. In contrast, clozapine-treated patients experienced significant symptom resolution and functional improvement. Fourteen physicians completed the survey, with a strong majority preferring quetiapine due to perceived ease of use and difficulties associated with clozapine blood monitoring. While acknowledging quetiapine’s limited effectiveness, physicians prioritized safety, feasibility, and logistical considerations over optimal symptom control.

Conclusion: The study reveals a critical misalignment between patient-reported outcomes and physician prescribing practices in PDP management. Patients prioritize symptom control and restoration of autonomy, whereas physicians often emphasize treatment feasibility and patient safety. These findings underscore the need for structural reforms to facilitate integration of clozapine monitoring into outpatient care and for systematic inclusion of patient-reported outcomes into routine clinical decision-making. Addressing these gaps is essential to achieve truly patient-centered pharmacotherapy for Parkinson’s disease psychosis.

References

[1] Burchill E, Watson CJ, Fanshawe JB, Badenoch JB, Rengasamy E, Ghanem DA, Holle C, Conti I, Sadeq MA, Saini A, Lahmar A, Cross B, McGuigan G, Nandrha A, Kane EJ, Wozniak J, Farouk Ghorab RM, Song J, Sommerlad A, Lees A, Zandi MS, David AS, Lewis G, Carter B, Rogers JP. The impact of psychiatric comorbidity on Parkinson’s disease outcomes: a systematic review and meta-analysis. The Lancet regional health. 2024 Feb 9;39:100870. DOI: 10.1016/j.lanepe.2024.100870
[2] Iketani R, Furushima D, Imai S, Yamada H. Efficacy and safety of atypical antipsychotics for psychosis in Parkinson’s disease: A systematic review and Bayesian network meta-analysis. Parkinsonism & related disorders. 2020 Sep;78:82-90. DOI: 10.1016/j.parkreldis.2020.07.021
[3] Rose O, Huber S, Trinka E, Pachmayr J, Clemens S. Treatment of Parkinson’s Disease Psychosis – A Systematic Review and Multi-Methods Approach. Biomedicines. 2024 Oct 11;12(10):2317. DOI: 10.3390/biomedicines12102317
[4] Shotbolt P, Samuel M, David A. Quetiapine in the treatment of psychosis in Parkinson’s disease. Therapeutic advances in neurological disorders. 2010 Nov;3(6):339-50. DOI: 10.1177/1756285610389656
[5] Siskind D, Northwood K, Pillinger T, Chan S, Correll C, Cotes RO, Every-Palmer S, Hahn M, Howes OD, Kane JM, Kelly D, Korman N, Lappin J, Mena C, Myles N, McCutcheon RA; Clozapine Delphi Expert Panel. Absolute neutrophil count and adverse drug reaction monitoring during clozapine treatment: consensus guidelines from a global Delphi panel. The Lancet psychiatry. 2025 Jul 1:S2215-0366(25)00098-7. DOI: 10.1016/S2215-0366(25)00098-7
[6] Del Miller D. Atypical antipsychotics: sleep, sedation, and efficacy. Primary care companion to the Journal of clinical psychiatry. 2004;6(Suppl 2):3-7.
[7] Kasper S. Sedation is not the opposite of agitation. European Psychiatry. 2007;22:S89. DOI: 10.1016/j.eurpsy.2007.01.1167
[8] Rose O. Parkinson-Krankheit: Basiswissen. Medizinische Monatsschrift fur Pharmazeuten. 2016;39(7):277-81.