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Parkinson's Disease and Parkinson's Disease Psychosis: A Perspective on the Challenges,Treatments, and Economic Burden
Doral Fredericks, PharmD, MBA; James C. Norton, PhD; Carolyn Atchison, MSc; Robert Schoenhaus, PharmD; and Michael W. Pill, PharmD

Parkinson's Disease and Parkinson's Disease Psychosis: A Perspective on the Challenges,Treatments, and Economic Burden

Doral Fredericks, PharmD, MBA; James C. Norton, PhD; Carolyn Atchison, MSc; Robert Schoenhaus, PharmD; and Michael W. Pill, PharmD

Parkinson’s disease (PD) is a progressive neurodegenerative disease associated with a decrease in the neurotransmitter dopamine and characterized by the cardinal motor hallmarks of resting tremor, rigidity, bradykinesia/akinesia, and postural instability. Lesser-known features of PD revolve around nonmotor concerns including psychosis, dementia, sleep disturbances, autonomic dysfunction, and sensory abnormalities. Parkinson’s disease psychosis (PDP) contributes significantly to morbidity, mortality, nursing home placement, and quality of life (QOL). PDP management suffers from a lack of safe, effective pharmacological agents and the opposing nature of atypical antipsychotics and dopaminergic therapies. Pimavanserin, the only atypical antipsychotic currently approved by the FDA for treating PDP-related hallucinations and delusions, has no appreciable affinity for dopaminergic receptors, and a controlled clinical study demonstrated its efficacy in treating PDP-associated hallucinations and delusions without affecting motor function. A recent analysis of all health resource utilization (HRU) and total costs attributable to PD and PDP found that mean 12-month HRU services per patient were 2.3 times higher and costs were 2.1 times higher in the PDP cases, while falls were 3.4 times higher and fractures 2.3 times higher, respectively. Products or services that prevent, delay, or lessen the severity of PDP may contribute to reduced healthcare system costs and improve the QOL of patients with PDP and of their caregivers. Am J Manag Care. 2017;23:-S0

An Overview of Parkinson’s Disease and Parkinson’s Disease Psychosis

Parkinson’s disease (PD) is a progressive neurodegenerative illness associated with degeneration of dopaminergic neurons and the consequent decrease in the neurotransmitter dopamine, resulting in both motor and nonmotor changes.1,2 It is the second most common neurodegenerative disease after Alzheimer’s disease,3 affecting up to 1 million Americans and more than 10 million individuals worldwide.4 As the elderly population grows, the incidence of PD is expected to double by 2030 in Western Europe’s 5 most and the world’s 10 most populous nations, including the United States.5 Approximately 20% of individuals with PD are diagnosed before age 65.6 The combined direct and indirect costs of PD, including treatment, Social Security payments, and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States alone.4

The main clinical features of PD are motor symptoms, as described by the mnemonic TRAP (tremor, rigidity, akinesia, and postural instability),7 but the cognitive and behavioral nonmotor features of PD are often reported to be more disabling.8,9 These include autonomic dysfunction, impaired sense of smell, gastrointestinal disturbances, and psychiatric symptoms such as sleep disturbances, depression, impulse control disorders, dementia, and psychosis, as defined by hallucinations and delusions.10,11 Parkinson’s disease psychosis (PDP) is one of the major challenges in the treatment of PD12 and involves a spectrum of symptoms beyond formed visual hallucinations.13 These can include presence or passage hallucinations (ie, the perception of an object or person present or moving in the visual periphery)14; complex visual hallucinations, usually of people, animals, or objects15; auditory, tactile, gustatory, and olfactory hallucinations that can occur on their own or with visual hallucinations11,16; and paranoid beliefs of infidelity or abandonment that involve spouses, family members, or other caregivers.17

Psychosis has long been thought of as primarily a consequence of dopaminergic therapies used to treat the motor symptoms of PD; however, it is increasingly recognized that dopaminergic therapy is neither necessary nor sufficient to completely account for the development of psychosis.13,18 More recently, these symptoms have been linked to the intrinsic processes of the disease itself. The complex pathophysiology of PDP remains unclear, but it may include visual processing abnormalities, sleep dysfunction, and specific neurochemical changes involving dopamine, serotonin, and acetylcholine.13 Risk factors/associations for PDP are listed in Table 1.19

Psychosis symptoms in patients with PD are a strong predictor of caregiver burden.20 PDP has a critical impact on both patients and caregivers; it is associated with a diminished quality of life (QOL),18 nursing home placement,21 worsening patient outcomes, and increased patient mortality.13,22-24 Once psychotic features are present, they tend to be recurrent and persistent.13,25

The Scope of PDP

The burden of PDP exists among patients with PD of all ages.26 Neuropsychiatric symptoms of PD, especially dementia, depression, and psychosis,27 significantly increase health service utilization and the risk for disability, hospitalization, and institutionalization.28,29 In contrast to motor symptoms, nonmotor symptoms are often unrecognized and untreated.30

The prevalence of PDP has been difficult to determine, primarily because of nonuniform methods of defining and measuring symptoms.13 Aarsland and colleagues reported an 8-year prevalence of dementia of 78.2% among patients with PD followed prospectively,31 while Hely and colleagues found a 20-year prevalence of 83%.10 In their 2010 study, Reidel and colleagues found that the prevalence of neuropsychiatric symptoms was greatest for insomnia (49.0%), anxiety (19.6%), and hallucinations (11.5%).27 Others have reported a lifetime prevalence rate for PDP of 25% in community-based populations and nearly 50% in clinic-based populations. However, the proposed diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health, which include the presence of illusions or a false sense of presence or passage in addition to the historical criteria of hallucinations and delusions, could raise the prevalence over the lifetime course of the disease.13

Common neuropsychiatric features of PD include the following:
Psychosis (hallucinations and delusions)13
Cognitive dysfunction (up to 44%, depending on the diagnostic criteria applied)32
Depression (52% occurrence in people with PD33; associated with higher daily doses of levodopa, the presence of mild cognitive impairment, and hallucinations)12,34
Dementia (48% prevalence in PD patients followed over 15 years)12
Confusion or delirium35
Impulse control disorders (occur in up to 14% of PD patients. The most commonly reported impulse control disorders in PD are compulsive gambling, buying, sexual behavior, and binge eating)36
Anxiety (also associated with depression)37
Apathy38,39
 
Patients often exhibit more than 1 symptom, with depression and/or dementia appearing as the most frequent comorbidities compared with other neuropsychiatric symptoms.27 Neuropsychiatric symptoms, especially depression and cognitive dysfunction, have the most detrimental impact on patient health-related QOL (HRQoL).8,40-42 Clinicians are frequently focused on treatment for the motor aspects of PD and may be inattentive to nonmotor and HRQoL issues,9,43,44 which can adversely affect adherence to treatment and negatively impact cost of care.45,46 Caregiver HRQoL can also be poor due to the physical and psychological disability associated with PD.47,48 In a study by von Campenhausen and colleagues (2011), more than half of family members providing care suffered from health problems themselves.49



 
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