Hallucinations and delusions associated with Parkinson’s disease psychosis: safety of current treatments and future directions

Isaacson, Stuart; Citrome, Leslie

doi:10.1080/14740338.2022.2069240

Cited by 10 publications

(7 citation statements)

References 60 publications

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“…A recent study reported a twofold increased risk of dementia after more than 3 months of antipsychotic treatment with second‐generation antipsychotics 55 . In the United States, pimavanserin is already approved by the Food and Drug Administration for PD patients and has been shown to have a better cognitive side effect profile than second‐generation antipsychotics 56 . Although we only looked at prescriptions 1 year before the current observation, the overall relationship between psychosis onset (and treatment threshold) and cognitive impairment remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

Fink,

Dodel,

Georges

et al. 2023

Movement Disorders

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ObjectiveThe aim of our study is to analyze sex‐specific patterns of Parkinson's disease dementia (PDD) incidence. We are investigating the extent to which sex differences in survival after initial Parkinson's disease (PD) diagnosis influence differences in PDD risk among PD patients.MethodsWe used a random sample of German longitudinal health claims data of persons ages 50+ (2004–2019; n = 250,000) and identified new PD cases ages 65+ who were followed‐up for a PDD diagnosis or death between 2006 and 2017. We performed Cox and competing‐risk regression models, with death as competing event, to calculate PDD hazard ratios (HR) adjusted for age at PD onset, PD severity as measured by the modified Hoehn and Yahr (HY) scale, comorbidities, and medications.ResultsOf 2195 new PD cases, 602 people died before PDD and 750 people developed PDD by the end of 2017. The adjusted risk of PDD differs by sex, with men having a higher PDD risk than women. When accounting for death, men and women do not differ in their PDD risk (HR = 1.02, P = 0.770). Sex‐specific analyses showed significant age and severity effects in women (age: HR = 1.05, P < 0.001; HY 3–5 vs. 0–2.5: HR = 1.46, P = 0.011), but not in men.ConclusionOlder age at first PD diagnosis and higher disease severity increase PDD risk, but this association is attenuated for PD men when controlling for death. This implies that the most frail PD men die rapidly before receiving a dementia diagnosis, whereas women with PD survive at higher rates, regardless of their age at onset and disease severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 99%

“…55 In the United States, pimavanserin is already approved by the Food and Drug Administration for PD patients and has been shown to have a better cognitive side effect profile than second-generation antipsychotics. 56…”

Section: Discussionmentioning

confidence: 99%

The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

Fink,

Dodel,

Georges

et al. 2023

Movement Disorders

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“…Several studies have shown an increased mortality rate associated with psychotic symptoms in PD 38 and have also shown a significant increase in mortality with the use of risperidone, quetiapine, and olanzapine, all second-generation neuroleptics, and conflicting results with pimavanserin. 38,39 The numbers of patients with PD treated with clozapine has been too small to be analyzed even in large databases. In addition, there are caveats in comparing mortality in second-generation neuroleptic treated versus untreated because of the limited ability to control for confounds.…”

Section: Mortality and The Black Box Warningmentioning

confidence: 99%

“…No death was attributed to clozapine. Several studies have shown an increased mortality rate associated with psychotic symptoms in PD 38 and have also shown a significant increase in mortality with the use of risperidone, quetiapine, and olanzapine, all second-generation neuroleptics, and conflicting results with pimavanserin. 38,39 The numbers of patients with PD treated with clozapine has been too small to be analyzed even in large databases.…”

Section: Mortality and The Black Box Warningmentioning

confidence: 99%

Clozapine Is Severely Underused in Parkinson's Disease Patients

Friedman

2022

Movement Disord Clin Pract

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“…The hallucinations related to PD are mainly visual, which can occur with other minor hallucinations such as a false sense of presence, a false sense of a passage, and illusions [ 9 ]. Interestingly, delusions are usually related to spouse infidelity, but they are less prevalent than hallucinations [ 10 ]. Some subjects can develop paranoia, but it does not present with unusual thoughts content as seen in individuals with schizophrenia [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Pimavanserin and Parkinson’s Disease Psychosis: A Narrative Review

et al. 2022

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Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson’s disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin’s history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD.

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Hallucinations and delusions associated with Parkinson’s disease psychosis: safety of current treatments and future directions

Cited by 10 publications

References 60 publications

The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

The Impact of Sex‐Specific Survival on the Incidence of Dementia in Parkinson's Disease

Clozapine Is Severely Underused in Parkinson's Disease Patients

Pimavanserin and Parkinson’s Disease Psychosis: A Narrative Review

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