Parkinson’s Disease Psychosis—A Symptom Complex Signaling Risk for Increased Disability and Caregiver Burden

US Neurology, 2015;11(1):23–6 DOI: http://doi.org/10.17925/USN.2015.11.01.23

Abstract:

Parkinson’s disease psychosis (PDP) occurs frequently in patients with Parkinson’s disease (PD) and involves a spectrum of symptoms, from mild hallucinations to those that are more disruptive, as well as delusions, particularly around spousal infidelity and theft of money or possessions. Risk factors for PDP include dopaminergic (and other) medications, cognitive disorders, sleep disorders, and duration of PD. Emerging evidence suggests that PDP also reflects underlying PD pathology. Routine querying of major PDP symptoms can hasten recognition and allow earlier diagnosis of PDP. Mild hallucinations with retained insight are frequent and may be tolerable by patients and caregivers, but symptoms that can be considered as psychosis will typically increase in frequency and severity. Increasing PDP results in patient distress, increased caregiver burden, and is a leading cause of long-term nursing home placement. PDP has also been associated with an increased risk for morbidity and mortality. Ongoing research into the prevalence, risk factors, phenomenology, pathophysiology, and emerging pharmacotherapy for PDP provides hope for improved diagnosis and management of PDP.

Keywords: Parkinson’s disease, psychosis, evaluation, caregiver burden, quality of life
Disclosure: Stuart H Isaacson has received honoraria for consulting and research grants from ACADIA Pharmaceuticals Inc.
Acknowledgments: Editorial assistance was provided by Catherine Amey at Touch Medical Media, London.
Received: February 13, 2015 Accepted March 10, 2015
Correspondence: Stuart H Isaacson, MD, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, US. E: isaacson@ParkinsonsCenter.org

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.
Support: The publication of this article was supported by ACADIA Pharmaceuticals Inc. The views and opinions expressed are those of the author and not necessarily those of ACADIA Pharmaceuticals Inc.

Parkinson’s disease (PD) is a progressive neurodegenerative synucleinopathy. Clinical diagnosis is based on the presence of motor symptoms, including bradykinesia, rigidity, rest tremor, and postural instability.1 Although the cause of PD is still unknown, the severe nigro-striatal dopamine loss provides the basis for dopaminergic treatment of motor symptoms. Nonmotor symptoms are also prominent, probably reflecting more widespread degenerative changes in PD, and include autonomic, enteric, and neuropsychiatric symptoms. Neuropsychiatric symptoms can be prominent, such as anxiety, depression, psychosis, sleep disturbances, and cognitive impairment.2,3 This has suggested to some that PD may be accurately described as a neuropsychiatric disease rather than a pure movement disorder.3

This review aims to characterize Parkinson’s disease psychosis (PDP). “Parkinson’s” and “psychosis” were used as search terms in a MedLine review between the date limits of 1990 and 2014. When selecting papers for inclusion in this review, priority was given to papers of higher relevance (as determined by the MedLine database) and to more recently published papers.

Prevalence and Incidence
The prevalence of hallucinations in PD in cross-sectional prospective studies varies widely, from 16 % to 75 % (see Table 1).4–7 In a Norwegian population-based prevalence cohort study, 230 patients with PD were followed up prospectively for 12 years.8 The point prevalence of PDP was 17.8 % (41/230) at baseline and increased to 48 % (12/25) at the 12-year visit. Over the course of the study nearly two-thirds of patients (60 %, 137 patients) had developed PDP during the course of their disease. The incidence rate of PDP was 79.7 per 1,000 person-years.

The variation in the reported prevalence of PDP may be due to differences in study design and patient selection, as well as inconsistencies in screening and patient or caregiver under-reporting.7,9

  • Patients may conceal their psychosis symptoms because of stigma associated with psychiatric disease, and fear of psychiatric hospitalization or long-term care placement.
  • Caregivers may be unaware of mild symptoms.
  • Physicians and other providers may be hesitant to query symptoms of psychosis.
  • Retained insight can make PDP symptoms seem mild and nontroublesome.
  • Cognitive impairment may impede evaluation of psychosis symptoms.6

For all of these reasons, PDP is probably under-recognized.7 Overall, this delay in recognizing PDP can lead to symptoms becoming severe before a diagnosis of PDP is made.7,10,11

Risk Factors and Emergence of Parkinson’s Disease Psychosis
The risk for developing PDP can be influenced by both endogenous and exogenous factors. Endogenous risk factors implicated in PDP include advanced age, severity of PD, duration of PD, depression, cognitive impairment, and sleep disturbances.7,8,12,13 Exogenous factors may trigger PDP to emerge, or may worsen mild or subclinical PDP. These can include systemic disorders, including urinary tract (or other) infections, dehydration, fever, and medications. Both dopaminergic and anticholinergic medications increase the risk for PDP. Indeed, medications used to treat the motor systems of PD may also trigger and/or increase PDP symptoms, including levodopa:8 as PD advances levodopa dosage tends to increase, with an increased risk for PDP. Other medications commonly used to treat PD motor systems may also increase PDP, especially dopamine agonists, selegiline, amantadine, and anticholinergics.13

PDP is often thought of as a side effect of dopaminergic therapy.14 Increasing evidence, however, suggests that PDP is a manifestation of the underlying neurodegeneration of PD and is related to progression of the underlying disease.12,14 Dosage and duration of dopamine replacement therapy have not been consistently correlated with PDP.12,15,16 In an evaluation of 422 patients with PD and hallucinations, drug treatment was not identified as a risk factor for emergence of hallucinations in PD.15 In addition, in a community-based study of 245 patients with PD, anti-parkinsonian drug therapy was not shown to be associated with psychosis.4 In a study evaluating intravenous levodopa in patients with PDP, visual hallucinations did not appear to correlate with higher plasma levodopa nor to sudden changes in plasma levodopa levels.17 A proposed pathophysiologic diagram of hallucinations in PD is provided (see Figure 1).

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Keywords: Parkinson’s disease, psychosis, evaluation, caregiver burden, quality of life