Background: Psychotic symptoms are a frequent and debilitating non-motor manifestation of Parkinson’s disease (PD), typically arising from the disease’s progression, the use of dopaminergic agents, or the development of Parkinson’s disease dementia (PDD). The therapeutic approach is often complex, as conventional antipsychotics may exacerbate parkinsonian motor symptoms due to their dopaminergic antagonism. 

Case Presentation: We report the case of a 71-year-old woman with a longstanding diagnosis of idiopathic PD, under continuous neurological follow-up since 1997. In 2013, the patient developed progressive cognitive impairment with spatial and temporal disorientation, meeting criteria for PD-related dementia. From 2017 onwards, she began experiencing recurrent episodes of paranoid delusional ideation and complex auditory and visual hallucinations. Partial symptom control was achieved after the withdrawal of amantadine and pramipexole, and the introduction of low-dose quetiapine (50 mg/day). Despite its dose optimization, the psychotic episodes persisted. In October 2022, the patient presented to the psychiatric emergency service with an acute psychotic decompensation, characterized by pronounced psychomotor agitation, disorganized behavior, paranoid delusional speech, auditory hallucinations, and frangophilic content. That same day, clozapine was initiated at 25 mg/day and carefully titrated to 100 mg/day, under weekly hematological monitoring. The patient exhibited a marked and sustained clinical improvement, with complete remission of psychotic symptoms and a concurrent reduction in choreiform motor phenomena. 

Discussion: Psychosis in PD is multifactorial and often requires a delicate balance between managing neuropsychiatric symptoms and preserving motor function. While quetiapine is commonly used due to its relatively favorable motor safety profile, evidence supporting its efficacy remains limited. Clozapine is the antipsychotic with most robust evidence of efficacy in PD-related psychosis, particularly in refractory cases, although its use is restricted by the need for regular blood monitoring due to the risk of agranulocytosis. This case illustrates the successful use of clozapine in a complex clinical scenario, with improvement across both psychiatric and motor domains. 

Conclusion: Clozapine represents a highly effective treatment option for refractory psychosis in patients with Parkinson’s disease, provided that hematological monitoring is feasible. Its dual benefit on psychotic symptoms and motor function underscores its value in selected clinical contexts.

TBA