As a neurodegenerative disorder, Parkinson’s disease (PD) is characterized by a combination of premotor, motor, and nonmotor symptoms. PD is commonly accompanied by psychosis, which is one of the commonest symptoms in the long run. As a result of Parkinson’s disease psychosis (PDP), symptoms can range from minor consequences of the disease (illusions, passage hallucinations, and presence hallucinations), to visual and nonvisual hallucinations and delusions. PDP is associated with a reduction in function and a reduction in quality of life as well. It is commonly believed that PDP is related to economic burden, and it has a significant impact on the utilization of long-term care services. The main focus should be on diagnosing, classifying, and managing PDP in an appropriate manner. As a first step in the management of PDP patients, the emphasis should be on identifying and treating any contributing medical factors, reducing or discontinuing medications that could cause or worsen psychosis, as well as nonpharmacological strategies and considering acetylcholinesterase inhibitors for treatment when dementia is present. A number of medications are being considered for use in PDP, including pimavanserin, quetiapine, and clozapine. The purpose of the current review is to provide a comprehensive understanding of the disorder in the general population with PD, including epidemiology, psychotic symptoms, risk factors, triggers, neuro-signaling pathways, diagnosis, and treatment of PDP.

It is known that Parkinson’s disease (PD) is a neurodegenerative illness that leads to progressive disability. A loss of striatal dopaminergic neurons in the substantia nigra pars compacta (SNpc), which project to the dorsal striatum, is commonly observed. It is characterized by a decrease in the neurotransmitter dopamine throughout the brain, leading to premotor, motor, and nonmotor symptoms [1-5].

PD patients experience motor features, including resting tremors, bradykinesia, and muscular rigidity with postural instability, often appearing as the disease progresses [6]. Nonmotor symptoms of PD, including cognitive impairments and behavior problems, are generally reported to be more disabling than the motor symptoms of the disease themselves [5,7,8].

There are several non-motor symptoms of PD which include autonomic dysfunction, pain, sleep disruptions, impaired sense of smell/olfactory deficits, gastrointestinal disturbances, cognitive impairment such as subjective cognitive decline, mild cognitive impairment, and dementia, as well as depression, impulse control disorders, and psychosis [9-14]. A summary of all the premotor, motor, and non-motor symptoms can be found in Table 1.

At the histological level, the progressive SNpc degeneration correlates with the accumulation of large intra-cytoplasmic inclusions, namely Lewy body (LB) containing misfolded α-synuclein (α-syn), neurofilaments, and ubiquitin, although α-syn deposition occurs years before motor presentations begin [16-20]. Up to one million Americans and more than 10 million individuals around the world are affected by this disease [21], which is the second most common neurodegenerative disease after Alzheimer’s disease [22,23].

There is no exact explanation of the etiology of PD, but it is believed that a combination of both environmental and genetic factors may contribute to the disease [24-26]. Among the general population, it is estimated that the prevalence of the disease is between 0.3 and 1.0% and that the incidence of the disease among those aged over 80 is approximately 3.0% [27-30]. In terms of incidence ratio, it has been observed that PD is more prevalent among males than females by an average of 2:1 [31-35].

It is expected that by 2030 that the incidence of PD will double in the five most populated nations in Western Europe and the 10 most populated countries in the world, including the United States because of the growing elderly population [36-40]. The incidence and prevalence of PD increases with age and is most commonly seen in people over the age of 50 [41-44]. It is estimated that 20% of individuals with PD will be diagnosed before they are 65 years old [45-47].

As the population ages with an increased life expectancy, the prevalence of PD is expected to increase dramatically over the next few decades [38,48]. This will be a consequence of the changing demographics of an aging population. There are approximately 930,000 individuals in the United States over the age of 45 who suffer from PD, and by 2030, that number is expected to rise to 1,238,000 individuals [40,44]. According, to the National Institute for Health, average annual costs related to PD in the United States alone are estimated to be more than $25 billion, taking into account direct and indirect costs such as treatment, Social Security payments, and lost income from inability to work [21].

As one of the greatest challenges in the treatment of PD, Parkinson’s disease psychosis (PDP) encompasses a spectrum of symptoms that go beyond just formed VHs and is considered to be one of the major challenges for treating neurologists and physicians [49-54]. It is possible to experience presence or passage hallucinations (i.e., seeing an object or person moving in the periphery of the eye) [51]; complex VHs involving people, animals, or objects [52]; auditory, tactile, gustatory, and olfactory hallucinations, which can occur independently or in combination with VHs [55,56]; and paranoid beliefs involving spouses, family members, or caregivers [57].

The most common symptoms of PDP are VHs, which have been reported in up to 65% - 75% of patients [58,59]. The prevalence of hallucinations has been found to be 50% in patients with PD after 15 years, and 70% after 20 years [60].

For a long time, it has been believed that psychosis is primarily due to the use of dopaminergic treatments in the treatment of PD motor symptoms. In spite of that, it has become increasingly apparent that dopaminergic therapy is neither necessary nor sufficient in order to completely explain how psychosis develops [53,61]. Recently, it has been found that these symptoms may be caused by intrinsic processes within the disease itself [62,63].

As a result of these differences in clinical features observed in PDP, it is important to remember that it differs from other psychotic diseases like schizophrenia or mood disorders associated with psychotic phenomena. Therefore, the current diagnostic criteria that are used in other mental health conditions may not be adequate for describing PDP’s diversity [64].

A strong correlation exists between psychosis symptoms in patients with PD and caregiver burden [65-70]. There is no question that PDP has a significant impact on both patients and caregivers alike. There are numerous outcomes associated with this condition, including an impaired quality of life (QOL) [61], placement in a nursing home [71,72], deteriorating patient outcomes, and an increased risk of death even [53,73-75]. If psychotic features are present in a patient, they tend to persist and become recurrent over time [53,76-79].

Although the complex pathophysiology of PDP remains elusive, it is believed that it is associated with abnormalities in visual processing, sleep disturbances, and specific changes in dopamine, serotonin, and acetylcholine signaling [53,80-82]. Increasing levels of sensitivity in the mesolimbic and mesocortical areas of the brain are considered to be one of the factors that contribute to psychosis, according to the dopamine hypothesis. Furthermore, it is also hypothesized that the serotonergic and the acetyl-cholinergic systems also play a role in PDP, either by disrupting the equilibrium between serotonin and dopamine or by causing a deficit in cholinergic neurons [83-88].

Published data on the annual incidence of PDP are scarce. The authors of a recent study conducted an incident cohort study from 1991 to 2010 in Olmsted County, Minnesota, to investigate the incidence of PDP, as well as to investigate their survival. In this study, they found that the incidence of PDP was 4.28 per 100 person-years in their cohort. There was also an increase in the risk of death by 71% among PDP patients compared to patients with PD. As compared to women, men had a 73.4% higher risk of death when they were PD patients without psychosis, while there were no significant differences in sex between those who were PD patients with psychosis and those who were not. In their study, they found that patients with PDP were more likely to die than patients with PD. In PD without psychosis, the odds of death were higher for men than for women; however, in PDP, the odds of death were comparable regardless of gender [89].

PDP’s prevalence has been difficult to determine, mainly because of the non-uniform methods of defining and measuring symptoms, resulting in a wide variance in how prevalent it is from one part of the world to another [53,90]. It is important to note that the samples of patients collected in earlier studies are generally cross-sectional, with prevalence rates ranging from 16% to 75% [91-103]. According to the NINDS/NIMH (National Institute of Neurological Disorders and Stroke/National Institute of Mental Health) criteria for PDP, 113 patients with PD were evaluated in an outpatient clinic setting and 60 percent of them were found to have psychotic symptoms [104].

As a whole, the prevalence of the disorder was higher than the definitions that the authors used (such as questionnaires and Diagnostic and Statistical Manual of Mental Disorders [DSM] criteria [60% vs. 43%), mainly due to the fact that the study included the less common visual illusions (27%) and minor symptoms (45%), as well as non VHs (35%). Using the same scale, a similar study of 250 community-based PD patients found a lower overall prevalence of 26% with any kind of psychosis and 52% with delusions. This result may be due to the fact that this study recruited subjects who had higher mini-mental state examination (MMSE) scores (i.e., > 24) than those in the previous study [105].

Across cross-sectional studies, there is a relatively homogeneous prevalence rate for complex VHs, with a range of 22% to 38% for the prevalence of these types of hallucinations. The values range from 0% to 22% for auditory hallucinations and even higher for minor psychotic symptoms (17% to 72%). Due to a number of methodological differences, and especially the wide variation in the range of psychotic symptoms that were investigated in these studies, it is difficult to compare the total prevalence of hallucinations or psychotic symptoms in general between these studies. There was no assessment of tactile hallucinations, olfactory hallucinations, or gustatory hallucinations, although these types of hallucinations may be more prevalent than previously assumed [106].

According to longitudinal studies of PD patients, a number of longitudinal studies have repeatedly been conducted to assess the prevalence of hallucinations at a given point in time. According to a selected clinic-based sample, the point prevalence rates for the disease in a determined population increased from 33% (n = 89) to 55% (n = 49) after 6 years [76], After 4 years, the prevalence of the disease in a community-based sample jumped from 23% (n = 82) to 56% (n = 68) [107] and in patients who were initially enrolled in a drug trial, the prevalence of the disease increased by 21% (n = 52) to 77% (n = 30) after respectively 15 and 20 years [108].

It is worth noting that two long-term studies included de novo patients participating in drug trials at the start. The prevalence of hallucinations over a period of four years in a four-year trial was 17% during that period [109]. In a 20-year follow-up of patients initially recruited in a bromocriptine trial, the period prevalence was 74% [108]. Analyses of psychotic symptoms among Southeast Asian patients with PD were conducted using a retrospective cohort of 336 patients. According to the study, psychosis was diagnosed in 63 patients with PD, which corresponds to an 18.8% prevalence of psychosis in this population.

In a retrospective study that examined a total of 445 patients who had died with a pathologically confirmed diagnosis of PD, 50% were found to have had a history of VHs and/or minor psychotic symptoms during their lifetimes [111].

In addition to the progressive nature of the disease, it has been reported that minor phenomena such as a sense of presence or visual illusions have an impact on 17% to 72% of patients, while VHs can have a life-time risk of up to 50% [112]. In community-based population studies, it is estimated that up to 60 percent of patients with PD will develop psychosis within 12 years of onset and that 27% of people with PD will experience psychotic symptoms within 19 months of being diagnosed [80]. As the disease progresses, psychotic symptoms often present sequentially in a series of stages, starting with a visual illusion, then transitioning to more severe hallucinations that include insight, hallucinations without insight, and then delusions [113].

Compared to those who are healthy, people with PD are six times more likely to develop dementia during their lifetime than those who are healthy [114]. According to a study by Fenelon and colleagues, 70% of patients with PD who also had dementia reported experiencing hallucinations, as opposed to 10% of those with intact neurocognitive functions. In addition, 55% of those with severe cognitive impairments reported hallucinations, as opposed to 8% of those with mild or absent cognitive impairments who reported hallucinations. An older age at onset and a longer duration of PD are two additional risk factors linked to the occurrence of hallucinations, and the presence of hallucinations for a longer period of time is an independent predictor of VHs [95].

There is a correlation between persistent psychosis and younger age at which PD onset occurs with a longer duration of the disease. An increased prevalence of paranoia has been found to be associated with nursing home placement [115]. Sleep disturbances are prevalent among PD patients and approximately 82% of those with PDP report sleep disturbances during the course of their disease [116]. The presence of VHs has been pointed out as a significant indicator of daytime somnolence [95].

Nature of psychotic symptomatology in PDP

As PD progresses over time, psychosis usually develops slowly and gradually over the course of the disease [80,117]. In most cases, the prodromal phase of the disorder is characterized by vivid dreams and nightmares [118,119]. During this phase, it is possible to develop illusions (e.g., people hidden behind curtains) as well as a false sense of presence (such as the sense of being in the company of others) [120].

Following this, patients tend to develop hallucinations in which they are still able to make sense of what is happening [58,121]. PDP on the other hand, has been associated with increased severity of motor system dysfunction in patients with hallucinations [50,121,122] Various studies have looked into hallucination by modalities [93,97,103,123,124]. It has been shown that VHs has been linked to retinal pathology, poor visual acuity, impaired color, and contrast discrimination, as well as abnormalities in higher-level processing in PD patients [125].

Typically, the content of these primarily VHs is recurrent in nature [126-129]. In addition, patients can develop hallucinations without being aware of their condition or having delusions [58,121]. Psychosis can occur with or without dementia, as well as spontaneously or due to the use of drugs, and the symptoms can occur either in the presence or in the absence of dementia [53,79,130,131].

There is no doubt that VHs has been considered to be the most characteristic feature of PDP, however, the spectrum encompasses a range of minor phenomena, hallucinations both visual and non-visual, as well as delusions.

It is considered among the minor phenomena that presence hallucinations (the delusion that someone or something is present), passage hallucinations (fleeting images viewed in one’s peripheral vision), and visual illusions (the misperception of external stimuli) occur. Minor phenomena are observed in 20% - 45% of individuals with PD [51,55,105,132] and these phenomena are frequently associated with hallucinations in 13%-27% of cases [55,105].

It is important to note that hallucinations in patients with PD can sometimes become a threat, but for the most part, they are not [124]. Despite this, they may still be distressing to some people [103]. The most common hallucination type is VHs [60,101,123,124], which occurs more frequently at night due to the dim lighting in the room [91,101,128]. Most of the time, these incidents are brief (a few seconds) and occur at least once a week [103,128]. The most common form of formed VHs involve people [91,103], but it is also possible for it to involve animals or objects as well [96,103]. The content can be either familiar or unfamiliar [133], black and white or colored [128], and of a normal size or distorted in some way [96,101].

People with non VHs are more prone to these experiences as they age [123] and they often co-occur with VHs [93,124]. The most common type of auditory hallucination is hearing human voices, but they can also include other sounds, such as animal noises [93,124]. In general, tactile hallucinations are predisposed to be stereotyped and are most often related to insects or small animals [124].

Although there are some similarities between the hallucinations caused by primary psychiatric conditions and those caused by PD, there are a number of differences between them as well. Schizophrenia hallucinations are most commonly auditory (although they are frequently multimodal), are more frequent, are more likely to be ego-syntonic, have an associated emotional valence, and are likely to result in a more negative impact on individuals than PDP hallucinations [134].

As opposed to hallucinations, delusions are fixed false beliefs that are less frequent than hallucinations. In general, prevalence estimates range from 3%-14% [105,135-139] and are higher when it comes to Parkinson’s disease dementia (PDD; 19%-51%) [140-142]. Infidelity is one of the most common themes of delusions [98], which are most commonly paranoid in nature. It was found that 2.5% of individuals with nontreatment naive PD exhibited delusional jealousy in a large cross-sectional study [143].

Capgras syndrome (the belief that familiar people have been replaced by imposters), Fregoli syndrome (the belief that familiar people appear as strangers), and reduplicative paramnesia (the belief that a person, place, object, or event has been duplicated) have also been described in PD [144,145] and 17% of individuals with PDD were affected by these conditions [146].

It is possible that psychosis can progress along a continuum in which minor phenomena evolve into hallucinations accompanied by retained insight to hallucinations accompanied by the loss of insight and the development of delusions [49].

There is a high probability that psychosis will continue to persist even after it has developed [56]. The results of a longitudinal study showed that, within three years, 81% of individuals who had hallucinations with retained insight began to experience hallucinations with loss of insight or delusions [147]. Based on a retrospective analysis of data from a small nonrandomized study, it appears that while both reducing the PD medications and initiating antipsychotic treatment result in an initial benefit, only the latter significantly delays the progression of hallucinations over time [148].

The amount of time individuals with minor phenomena were followed for a mean of 4.4 +/- 1.5 years in a longitudinal study of de novo PD [132]. There was a resolution of symptoms for 10% of the individuals, a stabilization for 52% of them, and a worsening for 38%. As part of another longitudinal study of de novo, untreated patients with PD, it was found that minor phenomena preceded formed hallucinations in about 50% of cases [113]. Additionally, it is important to note that the cognitive impairment of those with minor phenomena is not different from that of those without minor phenomena [132,149].

It was found in a cross-sectional study that there was an association between cognitive impairment and hallucinations, but not with delusions [150]. A new classification system for

PDP has recently been proposed by Factor, et al. which recognizes different subtypes of PDP and differentiates between them. Symptomatic psychosis has been divided into four classes, class I symptomatic psychosis, class II dopaminergic drug-induced psychosis (mostly delusions), class III psychosis, which is characterized by affective disorders and serotonergic dysfunction, and class IV psychosis characterized by cognitive decline and cholinergic dysfunction. It is important to note that only class IV psychosis is recognized as progressive and associated with a poor prognosis in this classification system [151].

Risk factors and triggers

In PD, the most frequent cause of admission to a nursing home is a psychotic episode, especially when delusions are the primary psychopathological symptom of the disease. It has been shown that there are a number of risk factors associated with PD, including exposure to Parkinson’s medications, an increase in executive impairment, an increase in the severity and duration of Parkinson’s disease, comorbid depression or anxiety, a comorbid sleep disorder, including rapid eye movement (REM) sleep behavior disorder and insomnia, as well as older age, global cognitive impairment, mild cognitive impairment or dementia, visual impairment, increasing fatigue during the day, and polypharmacy, particularly psychoactive drugs that are either prescribed or not [152,153].

Very well-defined medical conditions can trigger the onset of psychosis or increase the severity of symptoms which includes infection associated with fever, especially in cases of lower respiratory and urinary tract, dehydration, irregular or imbalanced nutrition, psychosocial stress or stressors, deprivation of or overload with sensory inputs such as loss of hearing aid, glasses, single room house, surgical operations, narcosis, metabolic alterations like hypo/ hyperglycemia, electrolyte imbalance (hyponatremia, hypocalcemia, hypomagnesemia), anemia, uremia, hepatic encephalopathy, hypovitaminosis (thiamine, folate, niacin, vitamin B12), hyper-/hypoparathyroidism, hyper-/hypothyreosis, and drugs (amantadine, anticholinergics, benzodiazepines, beta-blockers, corticosteroids, ketamine, lithium, metronidazole, opioids, penicillin, theophylline, etc.) [59,154-157].

Economic burden

Although PD has significant economic costs, those costs are amplified in the case of patients who have also been diagnosed with PDP, in addition to PD. In a recent study, the the odds ratio for PDP in form of hallucinations to be in a nursing home is 16 times higher than for PD patients staying in the community [160].

Hue and colleagues (2005) estimated that almost 70% of PD’s total economic burden can be attributed to indirect costs including productivity loss and uncompensated care provided by family members during the course of the disease [158]. There is evidence to indicate that productivity loss is greatest in the later stages of the disease and should be considered [159]. Even in the first year after diagnosis, indirect costs associated with lost productivity among the patient and caregiver were responsible for 45% of total expenditures in the first year following diagnosis [160-163].

Impact on long-term care utilization

No matter what the age of a patient is, there is a strong correlation between symptoms of psychosis and placement in a nursing home [76,164]. An analysis of claims data for commercially insured patients with Parkinson’s disease under the age of 65 years (n = 1151) over a period of 10 years found that patients who required ambulatory assistance devices and institutionalization had 6 to 7 times the direct costs as those who did not require such devices or institutionalization. A total of 24% of patients with PD were diagnosed with mental disorders, 11% had neuropsychiatric disorders, and 10% had sleep disorders. There was a significant difference between the institutionalized cohort of patients with PD and matched controls in that 57% had mental disorders compared to 10%, and 29% had neuropsychiatric disorders compared to 4% [160].

It has been shown in an analysis of Medicare claim data from 2000 to 2010 that PDP imposes a heavy burden on Medicare. A total of 74.6% of patients with PDP spent 179 days on average in long-term care facilities (LTCs) as compared to 55.8% of patients with PD without psychosis (83 days on average). With regard to LTC in particular, the average annual all-cause cost for patients with PDP was $31,178, compared to $14,461 for those without psychosis who were suffering from PD. In terms of total reimbursement for all causes of care, the average annual reimbursement for patients with PDP was $67,251, while the reimbursement for PD patients without psychosis was $38,742 [162].

Neuroanatomy and neurochemistry

As far as PDP is concerned, the central dogma of the disorder is the overstimulation of the mesocorticolimbic dopamine receptors [165]. Overstimulation is caused by the interaction between the dopaminergic system and the serotonin system. Firstly, LBs that contain alpha-synuclein have been identified in the substantia nigra as well as the cerebral cortex as a significant disruptor of dopamine and serotonin transmission. There is an association between VH and high Lewy body densities in the amygdala and parahippocampal cortex [166-167].

There has been a suggestion since the early 1970s that serotonin and dopamine imbalance might contribute to PDP [168]. There was not much attention given to the possibility of serotonin being an element that could contribute to psychosis until it was discovered that lysergic acid diethylamide (LSD) and LSD-like hallucinogens could activate 5-HT2A receptors [169,170]. Atypical antipsychotics, such as clozapine and quetiapine, are also antagonists of both 5-HT2A/2C receptors, as well as dopamine D2 receptors, in low doses. This property has been suggested as a possible mechanism by which antipsychotics are effective in PD without worsening motor symptoms [171-173].

Using the selective 5-HT2A receptor ligand [18F]-setoperone PET imaging method, Ballager, et al. assessed in vivo changes in 5-HT2A receptor binding between PD patients without dementia with VHs compared with the PD patients without dementia with VHs [174].

It has been demonstrated that PD patients with VHs have increased 5-HT2A binding within the ventral visual pathway, which is composed of bilateral inferooccipital gyrus, right fusiform gyrus, and inferotemporal cortex. In addition, the bilateral dorsolateral prefrontal cortex, medial orbitofrontal cortex, and insula have been affected in PD patients with VHs. In contrast to patients who did not have VHs, another postmortem tissue study revealed that there was an increased binding of [3H]-ketanserin to 5-HT2A in the inferolateral temporal cortex of PD patients with VHs [175].

Nonmotor symptoms are associated with the degeneration of serotonergic neurons within the raphe nucleus, which is part of the limbic system [176-178]. There are two such symptoms associated with PDP, namely depression and anxiety, both of which are common [179-184]. It has been suggested that activities in the temporal cortex and visual pathways are likely a cause of VHs in PDP due to upregulation and overstimulation of cortical serotonin 5-HT2A receptors [84,175,185,186].

In the prefrontal cortex, the upregulation of dopamine receptors affects projections to the ventral striatum, which in turn regulates the release of dopamine from the brain [187-190]. It is known that dopamine binds to a variety of 5HT receptors, suggesting that dopaminergic agents may also play a role in the development of psychosis [191-194]. In comparison to levodopa, there is a higher risk of psychosis with dopamine agonists, which may be due to the stimulation of serotonin receptors, as opposed to levodopa [195-198].

There is no doubt that PD has a known cholinergic deficit that has been linked to psychosis in DLB [199-201]. Furthermore, there have been reports that anticholinergic drugs intended to treat motor symptoms of PD can cause psychosis [155,202]. The cholinesterase inhibitor rivastigmine demonstrated promising results that involved PD patients with dementia and DLB with VHs [203,204].

There is evidence that disrupting the ascending cholinergic transmitter system is associated with the denervation of the cortex frontal and degeneration of central cholinergic structures, such as the nucleus basalis of Meynert and pedunculopontine nucleus, which are responsible for attention, cognition, and RBD [205,206]. In PD patients, altered cortical processing of visual perception due to degeneration of cholinergic structures (i.e., PPN) may be associated with their VHs, and this has also been shown in VBM (Voxel-based morphometry) imaging by the volume reduction of PPN after 2.5 years of follow-up [207,208].

PDP may also exhibit a significant reduction in glutamatergic activity as a result of interactions between dopamine and glutamate in the dorsal striatum and nucleus accumbens of the brain. In patients with PD, it is known that the glutamate antagonist amantadine and memantine lead to VHs [209]. Earlier it was proposed that the etiology of PD was caused by reduced glutamatergic function, resulting in increased dopaminergic activity, leading to the development of psychosis in patients with the disease [210,211].

In a recent study using proton magnetic resonance spectroscopy (1H MRS), which measures metabolites in the brain, it was found that there were lower glutamate levels in the dorsal caudate and putamen of patients with PDP compared to those who did not have psychosis [212]. As compared to healthy controls, several hippocampal subfields in the hippocampal region have been observed to have atrophy in patients with PDP [213,214].

In a study done by Lenka, et al. abnormalities in white matter were found in patients with PDP who had fractional anisotropy in several areas of the brain, such as the inferior longitudinal fasciculus (ILF) and the inferior frontal-occipital fasciculus (IFOF). In addition to ILF and IFOF abnormalities, there is evidence that they contribute to VHs by disrupting the information processing from the orbitofrontal cortex to the occipital cortex [215].

PDP has a complex pathophysiology that has not been fully understood and is still under investigation. Dopamine receptor antagonists are used for the treatment of psychosis, while many dopaminergic PD medications exhibit high propensities for inducing psychotic symptoms as well [216]. The use of dopaminergic medications by patients with PD does not always result in psychosis, high-dose levodopa infusions do not cause hallucinations [217]. In addition, hallucinations can also occur in people with untreated PD [218], and it is estimated that 3 percent of those with untreated PD will develop psychosis [219,220].

According to the original hypothesis, there is a pharmacological kindling after chronic levodopa treatment, where dopamine is no longer being stored adequately on the presynaptic level. Thus, overflow and overstimulation of mesocorticolimbic postsynaptic dopamine D2 receptors in limbic areas and the cerebral cortex are thought to be involved in psychosis, similar to motor dyskinesia [221-223].

As evidence accumulates, it appears that D3 receptors have a minor modulatory effect on the function attributed to dopamine D2 receptors in the brain [224-233]. The results of a recent postmortem study using a D3-selective ligand, 3H-WC-10, showed increased D3 receptors in striatal regions of five patients with DLB/PDD, compared with cognition-intact elderly controls, and in patients with DLB/PDD who had hallucinations compared with patients without hallucinations [234].

The clinical features of PDD and DLB are similar, and VH is highly specific for LB parkinsonism (DLB and PD) in contrast to non-LB parkinsonism [111,235,236]. Despite the fact that both conditions are characterized by cholinergic dysfunction, it is possible that this system plays a role in PDP as well [125,237]. It is possible for anticholinergic medication to cause or contribute to impairments in cognitive function. In contrast, the cholinesterase inhibitor rivastigmine can be used to treat both DLB and hallucinations in PDD, as it inhibits cholinesterase activity [203].

VHs is associated with a greater level of amyloid plaque and neurofibrillary tangles in the cortex and amygdala of PD patients, as well as more cortical and amygdalar LB pathology [214]. The work of Ffytche, et al. suggests that the progression of psychosis from the brain stem to the basal forebrain to the cortex is similar to the progression of LB pathology from the brainstem to the cortex [49].

Postmortem studies have investigated potential links between visual hallucinations and pathology within the LC and SN, yet have found no such associations [238]. A study looked at the correlation of brainstem pathologies with PDP in a cohort of 175 patients. They semi-quantitatively analyzed the brains to ascertain the burden of neuronal loss and gliosis and LB pathology within the LC and SN. Around 56% of patients in the whole sample had the diagnosis of psychosis. The authors found out psychosis was associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. Psychosis was not found to be associated with LB score. They concluded PDP is associated with the underlying neurodegenerative process and demonstrated that cell loss and gliosis may be a better marker of psychotic symptoms than LB pathology [239].

Neuro-signaling pathways and network changes in PDP

It has been proposed that various hypothetical frameworks can be used to explain VHs, including the possibility of endogenous imagery being absorbed while dreaming [240], a deficit in reality monitoring that causes the perception [241] to be indestructible, the dysregulation of internal and external imagery [242], the impairment of the interaction between attention and perception [243], and the dysfunction of attentional networks [244].

In the study by Stebbins, et al. it was argued that the top-down, internally driven process of attentional cortex processing is disinhibited when compared to the usual, externally driven, bottom-up process [245].

A decrease in cortical activation was found in the posterior region of the brain (i.e., the middle temporal and occipital regions, parietal regions, and cingulate regions) in the study, which could be associated with reduced visual attention to external perceptions. It was found that patients with PD with VHs demonstrated increased activity in the frontal cortex (the superior and inferior frontal cortex as well as the caudate nucleus). As a result of a disruption of visual signal input, the retinal striatal cortical signals may be impaired due to reduced retinal dopamine and decreased striatonigral input, which, in turn, may result in abnormal activation of visual areas, and difficulty distinguishing between relevant and irrelevant visual information. A second hypothesis, supporting the notion of a bottom-up impairment in perceptional visual cortex processing, was supported by the study conducted by Meppelink, et al. [246].

As a result of impaired bottom-up processing in PD with VHs, the lateral occipital cortex and extrastriate temporal visual cortex were not activated as much as they should have been just before image recognition. However, it was not evident that there was a compensatory ‘top-down’ cortical response.

It has been found, however, that an impaired “top-down” response may be attributed to decreased activation of the frontal gyri. A reduction in the activation of the occipitotemporal cortex, as well as an impairment in the integration of sensory and mnemonic information, may all contribute to visual impairments in patients with PD as well as a reduction in the activation of the frontoparietal cortex, which can suppress irrelevant stimuli.

A comprehensive assessment of the clinical, demographic, and ophthalmological correlates of VHs in PD has been provided by Gallagher, et al. which supports the hypothesized model of impaired visual processing, sleep/wake disturbance, and brain stem dysfunction, as well as cognitive dysfunction. In PD, there is a variety of impairments, particularly frontal, thereby contributing to the pathogenesis of VHs, which are further bolstered by higher cortical LB counts in areas associated with visuo-perception and executive function that were associated with increased VHs [238].

In a recent study, researchers used a novel experimental priming task that used top-down verbal cues to prime the recognition of partial or ambiguous images from the bottom up, challenging the previous hypothesis, which demonstrated that VHs in PD are normally activated from the top down as well as interact between the top-down and bottom-up processes [247].

In a study conducted by Firbank, et al. using magnetic resonance spectroscopy in 36 patients with PD, it was found that in patients with VHs, the ratio of aminobutyric acid/creatine in the occipital lobe was lower than in patients who did not exhibit psychotic symptoms; furthermore, gray matter loss was observed in the anterior temporal lobe, as well as the visual cortex in the V4 region [248].

There was a reduced amount of gray matter atrophy in the visuoperceptive areas of patients with PD with minor hallucinations [249,250]. An analysis of neural networks and structure was conducted by Zarkali, et al. using fixed-based analysis. According to their findings, PD patients with hallucinations had degenerated and decreased posterior thalamic projections in the inferior frontal-occipital white matter tracts, suggesting that the splenium and posterior thalamus may play a large role in maintaining network balance and regulating the default mode network in PD [251].

Genes and PDP

There is no clear indication that there is an association between the genes that cause PD and the risk of psychosis. It is noteworthy, however, that with the exception of polymorphisms in genes associated with the cholecystokinin system, most of the conclusions regarding the other studies were inconsistent in regards to predicting the development of any psychotic profile in someone with PD [252].

Autosomal dominant genetic PD synuclein [SNCA] and leucine-rich repeat kinase 2 [LRRK2]) or idiopathic non-genetic PD has been linked to psychosis as compared to autosomal recessive genetic PD ((e.g., parkin, PTEN-induced putative kinase 1 [Pink1] and DJ1). In an early systematic review of the prevalence of non-motor symptoms in genetic PD [48], it was found that the frequency of psychosis in genetic PD does not appear to be greater than in idiopathic PD (3%-29%), and in fact, may even be lower [94].

Taking all cases together, it has been found that psychotic symptoms are relatively rare in parkin-linked PD (about 3%) and other genetic forms of PD (SNCA, Pink1) compared to those resulting from idiopathic causes. Recently, there have been studies that have shown that parkin PD may also be associated with psychosis [253], but comparing parkin+ with disease-matched parkin- PD reported no real differences [254].

VHs have previously been found to be common psychotic symptoms in PD patients with duplications of the SNCA in previous studies [255,256]. In the longitudinal cohort study conducted on 215 PD patients and 126 controls over a period of 12 years, mutations in the glucocerebrosidase gene were identified as a susceptibility factor for early-onset psychosis in PD [257].

Due to the well-established association between psychosis and dementia in PD, as well as the relationship between the advanced stage of the disease and the emergence of psychotic symptoms, it has been proposed that APOE e4 may play a role in the development of PDP [258].

As a result of the presence of the APOE e4 allele in patients with PD without dementia who are taking levodopa, they have a higher risk of VHs [259]. There are, however, four other studies that have not confirmed the association between these two factors [260-263]. In fact, another study was able to show that having the APOE- e4 allele was positively associated with the occurrence of psychosis prior to cognitive decline and independent of age or cognitive status in patients with PD [264].

A study published showed that PD patients with the allele APOE-e4 are significantly more likely to develop hallucinations in the first five years of the disease as opposed to PD patients without the allele. However, it should be noted that the presence of APOE e4 was not associated with the occurrence of hallucinations five years after PD diagnosis in the current study [265].

There is an association between polymorphisms of the Dopamine Transporter (DAT) gene and neuropsychiatric disorders such as bipolar disorder and attention defiicit hyperactivity disorder [266]. There has been evidence that the 40-bp VNTR of the DAT gene is related to an increased susceptibility to PD [267-269]. It has been observed that psychosis is more common in levodopa-treated PD patients of Caucasian descent with psychosis than in those without psychosis who carried the nine-copy allele of the 40-bp VNTR of the DAT gene [270]. A recent study conducted in Serbia, however, revealed that there was no significant correlation between the 40-bp VNTR of the DAT gene and the risk of PD [271]. Two recent studies also did not show this association [272,273].

There is evidence that the -839 C > T allele of the 5’ UTR of the DAT gene is associated with VHs in patients with PD being treated with levodopa [272]. Among Brazilian PD patients with DAT1 rs28363170, a recent study showed that carrying the 10/11, 10/8, and 10/9 genotypes was more commonly associated with VHs, but there was no association found between DAT1 rs28363170 and VHs in the same study [274]. Additionally, a recent study from Slovenia has demonstrated that the haplotype of the SLC6A3 gene was related to the development of levodopa-induced VHs in patients with PD [275].

There is a significant increase in the risk of PDP associated with the use of dopaminergic agonists. Specifically, apomorphine, which has a higher affinity for DRD4 than DRD2 and DRD3, exhibits a modest hallucinogenic effect, and pergolide, which has a greater affinity for DRD2 and DRD3 than DRD4, is significantly associated with hallucinations. The development of hallucinations in PD has been proposed to be a result of hypersensitivity of the dopaminergic mesocorticolimbic system, especially those that occur early in the course of the disease and are not generally associated with cognitive decline [276].

In a study conducted among Japanese subjects, it has been reported that the genotypes TT and CT at the -45 locus, which is located in the promoter region of the CCK gene, have been associated with a higher frequency of hallucinations in patients with PD who have been given levodopa for treatment [278]. In a different study looking at the Chinese population, it was found that the T allele at the CCK -45 promoter region was associated with VHs in levodopa-treated PD patients [279]. A similar pattern of association between the CCK T allele and PDP occurrence was observed in another study aiming to confirm these findings in a white population. The CCK T allele as well as the combination of the CCK T and CCKAR C alleles were also found to be associated with PDP occurrence, though the frequency of the CCK T allele was relatively low, preventing statistically significant results from being obtained [280]. In another study, the polymorphisms of the CCK, CCKAR, and CCKBR genes were also not associated with the prevalence of PDP in a large study [281]. Therefore, it has been suggested that the effect of the gene polymorphisms related to CCK on the risk of PDP largely depends on the race and ethnicity of the population [281].

Several genetic variants affecting the HOMER1 promoter at rs4704559 and the C variant affecting the promoter at rs4704560 have been linked with an increased likelihood to develop hallucinations in those with PD [282]. In another study, the rs4704559 G allele of the HOMER1 promoter was shown to protect against the development of VHs in Brazilian patients with PD who were treated with levodopa [283].

PD patients with at least one of the COMT rs165815 C alleles are significantly less likely to have frequent levodopa-induced VHs compared to those without this specific allele, according to a study published recently [275]. In PD patients, it has been shown that the COMT-DDC gene–gene interaction affects the likelihood that they will experience VHs caused by levodopa [275].

The ACE-II genotype has been associated with a higher risk of levodopa-induced psychotic manifestations in Chinese patients with PD [284]. As a consequence, a study of Italian patients with PD found no association between ACE-II polymorphisms and PDP, indicating that any such relationship does not exist [285]. Apparently, the conflicting results of these studies may be accounted for by differences in racial or ethnic backgrounds.

It has been reported that polymorphisms in the Ankyrin repeat and kinase domain containing the I (ANKK1) gene have been associated with alcoholism and other neuropsychiatric disorders, including PD [286]. Another recent study showed that the GG rs2734849 ANKK1 gene polymorphism can lead to PDP among people with PD who have been treated with levodopa [271].

The FDA has approved a 5-HT2AR (serotonin 5-HT2A receptors) inverse agonist/antagonist, known as pimavanserin, as a treatment for PDP, further strengthening the hypothesis that serotoninergic function in the brain is critical to PDP development [287]. The results of another study showed that PD patients with dementia, as well as patients with dementia with Lewy bodies (DLBs), had a prevalence of delusions associated with the L/L genotype of the 5-HTTLPR (5-serotonin-transporter-linked promoter region) gene [288].

There are three genotypes of the MAPT (microtubule-associated protein tau) gene (H1/H1, H1/H2, and H2/H2). Postmortem study results demonstrated that PD cases with the H1/H1 genotype had significantly more hallucinations than non-carriers, regardless of the stage of their disease, compared to non-carriers with the H1/H1 genotype [263]. Another study, however, did not establish a relationship between MAPT gene polymorphisms and psychotic manifestations in patients with PD [260].

There is an association between high plasma levels of CRP (C-Reactive Protein) and the occurrence of hallucinations or illusions in patients with PD, suggesting that excessive systemic inflammation may be one factor that contributes to the development of this disease [289]. It has been demonstrated in a study that the IL-6 rs1800795 gene polymorphism is associated with a lower risk of patients with PD experiencing VHs [290].

Recently, GPX1 (Glutathione Peroxidase 1) rs1050450 gene polymorphism has been associated with a higher frequency of VHs in patients with PD [290]. In a recent study, it was demonstrated that the MAOB (Monoamine oxidase B) rs1799836 polymorphism protected against the development of PDP [290]. The BIRC5 (Baculoviral IAP Repeat Containing 5) rs8073069 polymorphism has been shown to have a protective effect against the development of VHs in patients with PD [290].

It has been demonstrated that the BDNF (Brain Derived Neurotrophic Factor) G196A polymorphism in PD was not associated with any non-motor symptoms, including psychiatric symptoms of the disease [291]. A recent study has shown, however, that BDNF Val66Met polymorphisms are associated with mild behavioral impairment (MBI) in patients with PD. It should be noted that Met carriers displayed a significantly increased level of impairment compared to Val carriers both in the subdomains of mood/anxiety and psychosis, which suggests Met polymorphism may increase the risk for PDP [292].

Diagnosis of PDP

As far as PDP is concerned, there is no standard way to diagnose it. The diagnostic criteria of PDP are summarized in the table below, which includes the NINDS-NIMH and DSM-V criteria. Gordon, et al. developed the modified NINDS criteria for a better understanding of PDP [293]. It is necessary to have both psychotic as well as Parkinson’s symptoms present. The diagnosis of PD is based on the criteria defined by the UK brain bank. The diagnosis of PDP requires that the onset of psychosis occur after the onset of symptoms of the disease. There is also a requirement to establish a symptom duration of more than one month and to exclude other conditions, such as DLBs, schizophrenia, or schizoaffective disorder, as well as other symptoms of schizophrenia [53].

There are several differential diagnoses to be considered, including, but not limited to, other neurodegenerative diseases, psychosis associated with the many causes of delirium, major depression, side effects related to dopaminergic medications, intoxication, and withdrawal states caused by other drugs and drugs of abuse as shown in Table 2 and 3.

Scales to assess psychosis in PD

The development of several scales has also led to the development of a variety of tools and methodologies for (1) assessing the probability of developing PDP [295], (2) confirming the presence of the disease, and (3) analyzing its severity.

A few of these scales are part of more general scales, such as the MDS-UPDRS [296], but others are incorporated as sub-scores into scales that are more specific to PD. The Parkinson Psychosis Questionnaire (PPQ) [297], the Scale for Assessment of Positive Symptoms (SAPS) [298], and the scale for the evaluation of neuropsychiatric disorders in PD (SEND-PD) [299] have been developed specifically to evaluate PDP.

A recommended selection of the available scales is summarized in the table below. Each scale has its particular strengths. It might be practical to integrate a psychiatric scale into a broader assessment of the patients, but in certain cases, it may be helpful to focus on the neuropsychiatric symptoms (NPS) in particular. For example, there are a number of tests that correlate well with the MDS-UPDRS, such as the SEND-PD, which has been shown to correlate with it [299], or the SAPS score, which also takes the impact of psychosis on the patient’s well-being and care.

Several scales were examined by the MDS in 2008 in order to diagnose PDP and concluded that it was impossible to use one scale to diagnose the condition effectively. According to their recommendation, there should be a combination of scales used depending on the patient’s needs. It was proposed by a task force of the MDS to begin by using scales geared toward diagnosing psychosis, such as the MDS-UPDRS, and then to use scales geared toward severity, such as the SAPS, both of which tend to focus on the severity of psychosis as shown in Table 4 [120].

Caregiver burden

An important component of the management of chronic illnesses has been the burden placed on caregivers. Caregiver burden can be attributed to a number of risk factors including female gender, a low level of education, living with the patient, a higher number of hours spent caring for the patient, depression, social isolation, financial stress, and a lack of choice in caring for the patient [300].

A significant caregiver burden is seen in PD patients with NPS such as anxiety, depression, and psychosis [301]. Family members are often the primary caregivers for patients who rely on their loved ones for physical, emotional, and financial support during their illness. Consequently, this places increasing stress on the caregivers, causing them to remain stressed, and as a result, they are at risk of deteriorating both mentally and physically in the long run [162]. It is for this reason that PDP is one of the main reasons for the placement of patients with PD in nursing homes [65,71]. According to Schrag and colleagues, the duration of the disease, the patient’s depression, hallucinations, and confusion are among some of the top contributors to caregiver distress.

In a study by Martinez-Martin, et al. which studies a sample of 584 pairs of PD patients and their primary caregivers. Patients’ NPS were measured with the SEND-PD scale, and the Zarit Caregiver Burden Inventory was used to quantify caregiver burden. There are strong associations between NPS and caregiver burden in PD, and caregiver burden is related to NPS in dementia patients, which is more prevalent and burdensome in this population [68].

Adelmen, et al. worked extensively in this field and they are of a view that it is possible to develop practical assessment strategies to evaluate caregivers, their care recipients, and the overall care needs of the care recipient in order to evaluate caregiver burden in a practical way. In the past few years, a variety of psychological and pharmacological interventions have been shown to have mild to moderate efficacy in reducing caregiver burden and associated symptoms of caregiver distress. Among the psychosocial interventions available to caregivers of dementia patients are support groups and psychoeducational programs. Researchers have found that caregiver burden-related symptoms (e.g., mood, coping, self-efficacy) can be improved even when caregiver burden itself is minimally improved [301].

Management of PDP

Pharmacological: To determine whether or not it is necessary to intervene in the case of PDP as a means of managing the individual, the initial step is to determine the severity and degree of symptoms. There are some PD patients who may not require treatment of illusions and some VHs, as they are regarded as not bothersome by them. As a matter of fact, some PD patients enjoy the experience and prefer to not receive treatment [302]. It is important, however, that such individuals be closely monitored for any changes in their symptoms, as their condition is prone to deterioration, especially if they suffer from any co-morbidity or intercurrent medical issues at the same time.

In order to treat PDP, the first step is to identify and treat any secondary causes, especially infection or febrile illness, metabolic disorders such as dehydration and electrolyte imbalance, as well as structural brain injuries such as subdural hematomas that may trigger acute psychosis in PD patients.

As a next step, it is necessary to review the drugs that have been prescribed. It is possible to experience psychotic symptoms as a result of taking a single PD medication (dopaminergic or non-dopaminergic) or combination of PD medications combined with many other medications, including those used to treat general medical illnesses [57]. It is therefore recommended that patients discontinue the use of all medications other than those that are essential for managing PD. These may include tricyclic antidepressants, antispasmodics (e.g., oxybutynin), anticholinergics, benzo-diazepines, muscle relaxants, and opioids.

If there are possible sequential symptoms, it may be necessary to clarify the time when recent medications were started or changed, and discontinue or reduce the medications if necessary. In order to obtain the best results, it is advised to modify the PD drugs, and to gradually remove them from the patients’ system in the following order: anticholinergics, monoamine oxidase B inhibitors (MAOBIs), amantadine, DAs, COMT inhibitors, and finally, levodopa [303].

In any case, it is necessary to always ensure that the motor function remains as normal as possible while stopping any PD medication, and it may be necessary to replace the PD medication with equivalent amounts of levodopa in cases where this is needed. One of the most important things to note is that it is not uncommon for PDP (as discussed above) not to be directly linked to dopamine drugs and some symptoms might not even go away after stopping the medication or reducing its dosage.

Upon examining a cohort of PD patients with psychosis after being adjusted to medications and managed for systemic illnesses, Thomsen, et al. found 16 (62%) of the 26 subjects who were enrolled in this study had sufficiently resolved their psychotic symptoms in the short term to not require antipsychotic drugs to be prescribed [304].

Having observed these results, it is advisable to investigate whether there is any underlying systemic illness that may cause the psychotic symptoms and determine whether there are any medication adjustments that may be needed to resolve them. Adding an antipsychotic agent is an option if the simplification and reduction of the PD medications to the lowest tolerable dose without resulting in an exacerbation of motor symptoms does not improve psychosis symptoms.

Antipsychotics or dopamine D2 receptor antagonists

A specific pharmacological management of psychotic symptoms using antipsychotics in PD is challenging in light of the potential for worsening of PD motor symptoms as a result of blocking the dopamine D2 receptors, as well as the undesirable side effects. In order to minimize the risk of aggravating parkinsonism, all typical and most atypical antipsychotics with a high risk should be avoided. Several reports have been published indicating that so-called atypical antipsychotic medicines can exacerbate the motor symptoms of PD which includes risperidone [305,306], olanzapine (and with no improvement in VHs) [307,308], ziprasidone [309,310] and aripiprazole [311,312].

It is also important to remember that antipsychotics carry a ‘black box warning’ from the US Food and Drug Administration (FDA), for use in elderly patients, especially those with underlying dementia, due to increased risks of all-cause mortality and cerebrovascular events as a result of their use [313]. The risk of death is reported to increase with an increase in the daily dose and/or with an increase in the duration of use, indicating that there is a dose-response effect [314]. There has been a 1.53-fold increase in ventricular arrhythmias and/or sudden cardiac death with the use of antipsychotic drugs, according to one study [315]. It is always a good idea to perform an electrocardiogram to ensure that the QTc interval is normal in all cases.

The use of neuroleptics is also associated with serious complications, such as neuroleptic malignant syndrome in patients who are considered neuroleptic sensitive (e.g., those with advanced PD or DLB), and increased mortality rates with reports of prevalence of up to 40% have been reported in those who are exposed to such medications [316].

The counter argument for treating significant disabling symptoms with appropriate antipsychotics is that, regardless of these issues, psychotic symptoms are considered to be independent predictors of mortality in people with PD during a 12-year follow-up (HR 1.45) [317]. Also, earlier detection of mild hallucinations and the use of antipsychotics may help to reduce the risks of later deterioration of mental health [318].

Brexiprazole

As a new partial agonist of D2 dopamine and serotonin 1A receptors, brexpiprazole is called a serotonin-dopamine activity modulator (SDAM), and as a potent antagonist of serotonin 2A receptors, noradrenergic alpha 1B and 2C receptors, it has a wide range of actions. In addition to being approved to treat schizophrenia, brexpiprazole can also be used as an adjunctive treatment for major depressive disorder (MDD). The study by Akimasa, et al. showed that brexpiprazole was effective in the treatment of PDP without any serious side effects. However, maximal dose should not exceed 4mg/day because of the risk of developing extrapyramidal symptoms [319].

Clozapine

A dibenzodiazepine, clozapine is a drug that has weak antagonism of the dopamine D2 receptor in the striatum as well as significant activity over the dopamine D4 receptor and the 5-HT2 receptor, especially at relatively low doses that are used in the treatment of PD [320]. Several studies have been conducted to test the efficacy of clozapine in PDP, both double blind and placebo-controlled. Currently, it is the only antipsychotic medication consistently found to be effective without worsening motor function, and it carries an acceptable safety risk when monitored regularly [321,322].

AAN evidence-based guidelines published in 2006 state that clozapine is currently the only antipsychotic with a recommendation level B recommendation that can be used in PDP [323]. There are similar conclusions to those found in the meta-analysis of 2007 [324] and the evidence-based medicine review by the MDS in 2011 [325]. At daily doses as low as 6.25 mg [322], PD patients can experience therapeutic benefit; the average effective dose for PD patients is usually between 25 and 50 mg per day.

Furthermore, it has been suggested that clozapine does not worsen motoric symptoms in PD as compared to other antipsychotics due to its fast-off dissociation from striatal dopamine D2 receptors, a phenomenon that is also associated with preferential dopamine D2 receptor occupancy in the temporal cortex compared to the putamen and the substantia nigra [326,327].

There are rare cases of non-dose-related agranulocytosis (prevalence 0.38%) [328] to be associated with clozapine use, which can be fatal. Because of this, absolute neutrophil counts need to be monitored and agranulocytosis can be reversed by stopping the medication immediately. There was an incidence of 8.3% of transient neutropenia observed in an eight-year follow-up study all of which resolved once the clozapine had been discontinued. [329]. In addition, the use of these low doses of the drug for long periods of time appears not to induce metabolic syndrome, which is commonly seen with the higher doses of the drug being used for schizophrenia. [330]. Postural hypotension and sedation are two of the more common side effects of this medication [331,332].

Quetiapine

As a dibenzothiazepine compound, quetiapine has a similar chemical structure to clozapine. It is also known to have moderate affinity for both dopamine D2 and 5-HT2 receptors with a much higher affinity for 5-HT2A receptors than for dopamine D2 receptors [333]. Aside from clozapine, it is also one of the medications commonly used to treat the psychoses associated with PD. It has been found, however, that quetiapine’s efficacy in clinical trials has been inconsistent [334-336].

Even so, low doses of quetiapine (25-75 mg/day) continue to be widely prescribed due to its low propensity to significantly worsen motor function during clinical trials, as well as the fact that it does not require regular blood screening. Accordingly, quetiapine has been classified as having Level C evidence, or evidence that lacks sufficient support, is associated with an acceptable safety risk, does not require specialized monitoring, but has implications for the practice of investigational drugs [337,338].

An open-label randomized trial found that a small percentage of patients taking quetiapine with severe parkinsonism who experienced mild exacerbations of the disease were elderly people with PDD, and who received a high dose of quetiapine. Therefore, patients with PDD are advised not to take quetiapine above 100 mg per day [339].

To compare the efficacy of clozapine and quetiapine in the treatment of psychosis in people with PD, two clinical trials have been conducted. Despite the fact that in one study the efficacy of quetiapine and clozapine appeared to be equal [339], the other study indicated that clozapine had a greater efficacy over quetiapine [340].

5-HT2A receptor ligands

Mianserin: Mianserin is a non-selective, clinically-available, anti-depressant that blocks 5-HT2A receptors [341]. Adjia, et al. looked at the effect of mianserin on the severity of psychosis and dyskinesia in the MPTP-lesioned common marmoset. They found mianserin was effective to alleviate both PDP and dyskinesia but with hinderance of L-DOPA antiparkinsonian action which was a limitation of its usefulness [342].

The non-selective inhibition of 5-HT2A-dependent mechanisms may be effective in treating PDP without worsening the motor symptoms of PD. It has been demonstrated that mianserin is the first non-selective 5-HT2 receptor antagonist that has been found to be effective at treating PDP after eight weeks in patients who have PD (n = 12) without showing signs of motor dysfunction [322].

Mirtazapine: Adija, et al. looked at the anti-psychotic potential of mirtazapine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset. The results of the study showed that mirtazapine had antipsychotic and antidyskinetic actions that did not interfere with L-DOPA’s anti-parkinsonian activity [343]. Several case reports also found out the efficacy of mirtazapine on nocturnal VHs and auditory hallucinations in PD patients without worsening the motor symptoms [344,345].

Pimavanserin: It must be noted that 5-HT2A receptors are constitutively active even in the absence of a 5-HT agonist, which means that an inverse agonist can be more effective at inhibiting such receptors than an antagonist can. The treatment of PDP can be made more effective by using 5-HT2A inverse agonists, which were suggested as potential therapeutic drugs [346,347].

With its low affinity for 5-HT2C and negligible binding to dopaminergic, adrenergic, histaminergic, and muscarinic receptors, pimavanserin is a selective inverse 5-HT2A receptor agonist, thus sparing atypical antipsychotics from the adverse effects of sedation and hypotension [348].

Using SAPS, a phase II study in 46 patients reported good tolerability over 28 days and a small reduction in psychosis compared to placebo [349]. After 6 weeks of taking pimavanserin 40 mg daily, a phase III randomized, double-blind, placebo-controlled study of 185 patients with PD showed significant improvements in SAPS scores (37% vs. 14%) as well as caregiver burden, daytime somnolence, and sleep quality [350].

A baseline ECG is needed before treating a patient with pimavanserin because it has the potential to cause QT interval prolongation. As many as eleven percent of the patients in the treatment group withdrew due to worsening psychotic symptoms during the trial. A meta-analysis of four RCTs (including two unpublished ones) evaluating pimavanserin’s antipsychotic efficacy in PD has been conducted by Yasue, et al.

The findings of this study indicate that pimavanserin is less likely to cause orthostatic hypotension and does not show significant differences in the incidence of all-cause discontinuation, adverse events, or death in this study. The researchers concluded that pimavanserin is effective in treating PDP with a good level of tolerability [351]. Recently, pimavanserin was approved by the FDA [322].

There is a recent post hoc study that used clinical trial data from 459 PD patients enrolled in the randomized controlled trials (RCTs) for pimavanserin in the treatment of PDP. A study reported a higher mortality rate (incidence rate ratio, [IRR] 4.20, 95% confidence interval, 2.13-7.96) in patients who used antipsychotics in comparison with those who did not [353]. In addition to this, other common side effects, such as sedation and orthostasis, should also be monitored closely.

Anti-dementia drugs

There seems to be a correlation between VHs and a faster rate of decline in cognitive function. Thus, it is logical to hypothesize that cholinesterase inhibitors may offer greater therapeutic benefits to PD patients with severe dementia who suffer from high levels of VHs. It is however important to note that to date, no double-blind, placebo-controlled studies have been carried out with the primary endpoint being the reduction of VHs. The majority of studies have been conducted using smaller groups, case studies, and open-label trials to assess the effectiveness of cholinesterase inhibitors in the treatment of PDP [354-357], while others have used VHs as secondary outcomes in studies where the primary outcome is to measure changes in cognitive abilities [358-361].

A number of studies have demonstrated the positive effects of cholinesterase inhibitors in the treatment of cognitive impairment, with subtle effects only observed on VHs but not on delusions, and without a significant impact on motor function. A significant number of patients, 7% - 10% of them, also reported worsening of their tremors as a side effect [362]. According to studies conducted to date, rivastigmine appears to be more consistently effective than donepezil in treating psychosis [359,361,363.

Anxiolytics and antidepressants

The psychological symptoms of depression and anxiety are often present in patients with PDP. It has therefore been suggested that either selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) could be used to treat both of these symptoms through an enhancement of serotonergic activity. It has been noted in a case series of eight patients with psychosis that acute reversal of psychotic symptoms can be observed with SSRI (citalopram) or SNRI (venlafaxine), either monotherapy or as an adjunct to PD treatment in patients with comorbid depression or anxiety [364].

Several case reports have reported that clomipramine helped reduce the symptoms of PDP, indicating that reducing co-existing anxiety and depression may have a separate effect on the symptoms of PDP as well [365]. Furthermore, there have been case reports of patients with PD suffering from acute psychosis as a result of taking fluoxetine [366] as well as mirtazapine [367]. At the present time, however, no RCTs have been conducted to identify the specific role that any antidepressant class plays in the treatment of PDP.

Other pharmacological therapies

The use of Yokukansan, a traditional Japanese medicine that consists of medicinal herbs, is approved in Japan for the treatment of anxiety and insomnia, as it has effects on the function of serotonergic receptors (5-HT1A and 5-HT2A). Studies have also shown that yokukansan has beneficial effects on neuropsychiatric symptoms associated with dementia, with good tolerability as well [368,369].

It has also been reported in a recent study that there is a tendency to improve delusions alongside significant improvements in hallucinations. It is important to note that motor functions did not undergo a significant change as a result of the treatment. Hypokalemia, listlessness, and drug allergies were some of the adverse effects associated with this medicine [370].

A study looked at the role of yokukansan for treating behavioral and psychological symptoms of dementia (BPSD) in patients with PD (n = 7) and those with PDD (n = 7). PD and PDD patients were treated for 4 weeks with yokukansan and the same patients were observed without yokukansan for 4 weeks. Psychological symptoms were evaluated every 4 weeks according to the Neuropsychiatric Inventory (NPI) scale. There was a significant improvement in psychological symptoms in the majority of patients with PD and PDD after 4 weeks of yokukansan treatment, especially in the incidence and duration of hallucinations [371].

Further, it is also reported that gabapentin was effective in treating an advanced case of PD with episodic VHs like insects and worms over the trunk and genital areas as well as asynchronous pain over the inguinal area. Despite the absence of any motor deterioration after gabapentin use, the disappearance of VHs suggests that there may be a possible involvement of the glutamic acid neuron system and/or the amino butyric acid neuron system in the VH disappearance and can be used as an alternative option in advanced PD [372]. During the course of taking gabapentin 300 mg orally five times a day for neuropathic chest pain following a coronary artery bypass graft surgery three years prior, a 65-year-old woman with no history of psychiatric illnesses developed VHs. A discontinuation of gabapentin led to the resolution of her hallucinations and was absent at 1 year of follow up. Taking gabapentin as a treatment for elderly patients must be done with the greatest care [373].

Nonpharmacological

Electroconvulsive therapy: It has been reported that there have been several small case series which have demonstrated that electroconvulsive therapy (ECT) has a beneficial effect on patients with refractory PD psychotic symptoms [374-376], as well as no change, or even improvement in symptoms related to motor function [377]. A meta-analysis looked at the role of ECT in non-motor symptoms especially NPS in PD. There was a significant improvement in depression and psychosis following ECT. It can be a useful tool in treating complicated PD patients [378].

In another study, it has been found that all patients who received ECT showed a statistically significant improvement in their Brief Psychiatric Rating Scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points), irrespective of whether or not they were experiencing psychosis or depression at the time. As an effective treatment for refractory NPS associated with PD, ECT has shown great promise [379]. Several case reports have shown the usefulness of ECT in drug induced psychosis especially caused by levodopa and other dopaminergic agents when used in idiopathic PD for longer duration and also in psychosis caused in cases secondary parkinsonism [380-384].

However, a case report also found out that there was a marked increase in parkinsonian symptoms and dystonia after ECT was administered to a patient with schizoaffective disorder and anticholinergic-refractory neuroleptic-induced parkinsonism. There has never been a report in the literature about this kind of unusual reaction of parkinsonian and dystonic symptoms to ECT [385]. One should continuously monitor for these uncommon side effects in PD patients when ECT is used.

DBS surgery

Several researchers have suggested that reducing the amount of dopaminergic medication after bilateral subthalamic DBS surgery may improve psychotic symptoms in PD patients 87[252]. A number of reports have also been published of stimulation-induced psychotic symptoms as well as transient manic psychosis following DBS surgery, which are likely to occur more frequently in older patients [386-388]. However, a recent case report described an acute-onset and reversible psychosis following DBS to the globus pallidus internus (GPi) [389].

Transcranial direct current stimulation

A shortage of well-designed, adequately powered RCTs is present for treating PDP. It was found that repeated consecutive sessions of occipital cathodal transcranial direct current stimulation (tDCS) and parietal anodal tDCS did not help in VHs associated with both PDD and DLB. Cognitive stimulation (attentional and visuoperceptual tasks) did not improve the condition [390].

Psychological approaches

It is also important to discuss non-pharmacological methods for managing psychosis and its behavioral and emotional consequences with the patient and his/her family. There is a tendency that PDP persists, and aggressive pharmacological treatments may not be able to resolve it. Additionally, psychosis is linked to other mental health conditions such as depression that are associated with disturbing emotions. An important element in optimizing psychosis management is the acquisition of self-management skills and the implementation of structured psychological interventions, despite the fact that both areas are understudied.

The effectiveness of psychotherapy as a primary intervention for PDP has not been studied in detail. However, clinical experience suggests that applications of cognitive behavioral therapy (CBT) techniques, such as stimulus control, caregiver skills training, family psychoeducation, and, to a lesser extent cognitive reframing, may be useful in treating the condition. In addition to CBT, caregiver management techniques may also help so as to improve the QOL for people with PDP by addressing modifiable risk factors such as healthy sleep habits, circadian rhythms, inaccurate beliefs about the meaning and cause of PDP, and the medications used to treat it, and by enhancing caregiver skills [390].

According to Diederich and colleagues, 36 out of 46 hallucinating PD patients who were surveyed reported using self-driven coping strategies in order to manage their symptoms, such as cognitive, interactive, and visual means. There was no formal measure included in the study to evaluate the effectiveness of these coping strategies, however patients who used these strategies found their hallucinations to be bothersome or depressing only 39% of the time, whereas patients who did not use these strategies found their hallucinations to be bothersome or depressing 60% of the time [391].

An array of psychosocial interventions has also been successfully used to treat the psychosis of PD patients, including CBT, supportive therapy, and psychoeducation [391-396]. Due to the fact that early psychosis in PD is often accompanied by retained insight, these patients are likely to benefit even more from such techniques as those described above.

The present review suggests that PDP is an important non-motor symptom that can predict a poor outcome in patients with PD. It has been suggested that dyshomeostasis of neurotransmitters, disruption of neuro-signaling pathways, and cognitive impairment contribute to the development of PDP. In the course of PD, onset and progression of psychosis are both associated with the side effects of anti-Parkinsonism medications and the patient’s specific characteristics. A number of therapeutic approaches are available to treat PDP, including the reduction or cessation of dopaminergic drugs, the use of antipsychotics, cholinesterase inhibitors, NMDAR agonists, and nonpharmacological interventions. It is still important in clinical practice to develop pharmacological interventions for PDP.

Future research should assess whether antiparkinsonian medications have any impact on the development and progression of PDP in a cohort of patients receiving different kinds and doses of antiparkinsonian medications, in order to determine whether antiparkinsonian medications have any significant impact. The emerging research on future targeted therapies which are based on new biomarkers and genetic factors may provide useful information for tailoring therapeutic strategies to each individual.

Funding: None

Thanks to my mentor Prof. Hui Fang Shang for constant support and Dr. Swati for PubMed literature screening.

1. Zaman V, Shields DC, Shams R, Drasites KP, Matzelle D, Haque A, Banik NL. Cellular and molecular pathophysiology in the progression of Parkinson's disease. Metab Brain Dis. 2021 Jun;36(5):815-827. doi: 10.1007/s11011-021-00689-5. Epub 2021 Feb 18. PMID: 33599945; PMCID: PMC8170715.
2. Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, Brown RG, Koller W, Barone P, MacPhee G, Kelly L, Rabey M, MacMahon D, Thomas S, Ondo W, Rye D, Forbes A, Tluk S, Dhawan V, Bowron A, Williams AJ, Olanow CW. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord. 2006 Jul;21(7):916-23. doi: 10.1002/mds.20844. PMID: 16547944.
3. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9. PMID: 12498954.
4. Zesiewicz TA. Parkinson Disease. Continuum (Minneap Minn). 2019 Aug;25(4):896-918. doi: 10.1212/CON.0000000000000764. PMID: 31356286.
5. Lee HM, Koh SB. Many Faces of Parkinson's Disease: Non-Motor Symptoms of Parkinson's Disease. J Mov Disord. 2015 May;8(2):92-7. doi: 10.14802/jmd.15003. Epub 2015 May 31. PMID: 26090081; PMCID: PMC4460545.
6. Moustafa AA, Chakravarthy S, Phillips JR, Gupta A, Keri S, Polner B, Frank MJ, Jahanshahi M. Motor symptoms in Parkinson's disease: A unified framework. Neurosci Biobehav Rev. 2016 Sep;68:727-740. doi: 10.1016/j.neubiorev.2016.07.010. Epub 2016 Jul 12. PMID: 27422450.
7. Witjas T, Kaphan E, Azulay JP, Blin O, Ceccaldi M, Pouget J, Poncet M, Chérif AA. Nonmotor fluctuations in Parkinson's disease: frequent and disabling. Neurology. 2002 Aug 13;59(3):408-13. doi: 10.1212/wnl.59.3.408. PMID: 12177375.
8. Frucht SJ. Parkinson disease: an update. Neurologist. 2004 Jul;10(4):185-94. doi: 10.1097/01.nrl.0000131146.08278.a5. PMID: 15245584; PMCID: PMC4119608.
9. Tibar H, El Bayad K, Bouhouche A, Ait Ben Haddou EH, Benomar A, Yahyaoui M, Benazzouz A, Regragui W. Non-Motor Symptoms of Parkinson's Disease and Their Impact on Quality of Life in a Cohort of Moroccan Patients. Front Neurol. 2018 Apr 4;9:170. doi: 10.3389/fneur.2018.00170. PMID: 29670566; PMCID: PMC5893866.
10. Bonnet AM, Jutras MF, Czernecki V, Corvol JC, Vidailhet M. Nonmotor symptoms in Parkinson's disease in 2012: relevant clinical aspects. Parkinsons Dis. 2012;2012:198316. doi: 10.1155/2012/198316. Epub 2012 Jul 25. PMID: 22888466; PMCID: PMC3410355.
11. Zhang TM, Yu SY, Guo P, Du Y, Hu Y, Piao YS, Zuo LJ, Lian TH, Wang RD, Yu QJ, Jin Z, Zhang W. Nonmotor symptoms in patients with Parkinson disease: A cross-sectional observational study. Medicine (Baltimore). 2016 Dec;95(50):e5400. doi: 10.1097/MD.0000000000005400. PMID: 27977578; PMCID: PMC5268024.
12. Ravan A, Ahmad FM, Chabria S, Gadhari M, Sankhla CS. Non-motor symptoms in an Indian cohort of Parkinson's disease patients and correlation of progression of non-motor symptoms with motor worsening. Neurol India. 2015 Mar-Apr;63(2):166-74. doi: 10.4103/0028-3886.156276. PMID: 25947979.
13. Sauerbier A, Jitkritsadakul O, Titova N, Klingelhoefer L, Tsuboi Y, Carr H, Kumar H, Banerjee R, Erro R, Bhidayasiri R, Schrag A, Zis P, Lim SY, Al-Hashel JY, Kamel WA, Martinez-Martin P, Ray Chaudhuri K. Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations. Neuroepidemiology. 2017;49(1-2):1-17. doi: 10.1159/000478702. Epub 2017 Aug 12. PMID: 28803229.
14. Sung VW, Nicholas AP. Nonmotor symptoms in Parkinson's disease: expanding the view of Parkinson's disease beyond a pure motor, pure dopaminergic problem. Neurol Clin. 2013 Aug;31(3 Suppl):S1-16. doi: 10.1016/j.ncl.2013.04.013. Epub 2013 Jun 14. PMID: 23931951.
15. Kalia LV, Kalia SK, Lang AE. Disease-modifying strategies for Parkinson's disease. Mov Disord. 2015 Sep 15;30(11):1442-50. doi: 10.1002/mds.26354. Epub 2015 Jul 24. PMID: 26208210.
16. Stefanis L. α-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a009399. doi: 10.1101/cshperspect.a009399. PMID: 22355802; PMCID: PMC3281589.
17. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012 Nov 16;338(6109):949-53. doi: 10.1126/science.1227157. PMID: 23161999; PMCID: PMC3552321.
18. Duffy MF, Collier TJ, Patterson JR, Kemp CJ, Fischer DL, Stoll AC, Sortwell CE. Quality Over Quantity: Advantages of Using Alpha-Synuclein Preformed Fibril Triggered Synucleinopathy to Model Idiopathic Parkinson's Disease. Front Neurosci. 2018 Sep 4;12:621. doi: 10.3389/fnins.2018.00621. PMID: 30233303; PMCID: PMC6132025.
19. Jan A, Gonçalves NP, Vaegter CB, Jensen PH, Ferreira N. The Prion-Like Spreading of Alpha-Synuclein in Parkinson's Disease: Update on Models and Hypotheses. Int J Mol Sci. 2021 Aug 3;22(15):8338. doi: 10.3390/ijms22158338. PMID: 34361100; PMCID: PMC8347623.
20. Meade RM, Fairlie DP, Mason JM. Alpha-synuclein structure and Parkinson's disease - lessons and emerging principles. Mol Neurodegener. 2019 Jul 22;14(1):29. doi: 10.1186/s13024-019-0329-1. PMID: 31331359; PMCID: PMC6647174.
21. Statistics on Parkinson’s. Parkinson’s Disease Foundation website. www.pdf.org/en/parkinson_statistics. Accessed January 10, 2016.
22. Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003 Apr 3;348(14):1356-64. doi: 10.1056/NEJM2003ra020003. Erratum in: N Engl J Med. 2003 Jun 19;348(25):2588. PMID: 12672864.
23. Lebouvier T, Chaumette T, Paillusson S, Duyckaerts C, Bruley des Varannes S, Neunlist M, Derkinderen P. The second brain and Parkinson's disease. Eur J Neurosci. 2009 Sep;30(5):735-41. doi: 10.1111/j.1460-9568.2009.06873.x. Epub 2009 Aug 27. PMID: 19712093.
24. Ball N, Teo WP, Chandra S, Chapman J. Parkinson's Disease and the Environment. Front Neurol. 2019 Mar 19;10:218. doi: 10.3389/fneur.2019.00218. PMID: 30941085; PMCID: PMC6433887.
25. Gallagher DA, Schapira AH. Etiopathogenesis and treatment of Parkinson's disease. Curr Top Med Chem. 2009;9(10):860-8. PMID: 19754402.
26. Jankovic J, Tan EK. Parkinson's disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):795-808. doi: 10.1136/jnnp-2019-322338. Epub 2020 Jun 23. PMID: 32576618.
27. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. doi: 10.1016/S1474-4422(06)70471-9. PMID: 16713924.
28. de Rijk MC, Breteler MM, Graveland GA, Ott A, Grobbee DE, van der Meché FG, Hofman A. Prevalence of Parkinson's disease in the elderly: the Rotterdam Study. Neurology. 1995 Dec;45(12):2143-6. doi: 10.1212/wnl.45.12.2143. PMID: 8848182.
29. Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm (Vienna). 2017 Aug;124(8):901-905. doi: 10.1007/s00702-017-1686-y. Epub 2017 Feb 1. PMID: 28150045.
30. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med. 2020 Feb;36(1):1-12. doi: 10.1016/j.cger.2019.08.002. Epub 2019 Aug 24. PMID: 31733690; PMCID: PMC6905381.
31. Gillies GE, Pienaar IS, Vohra S, Qamhawi Z. Sex differences in Parkinson's disease. Front Neuroendocrinol. 2014 Aug;35(3):370-84. doi: 10.1016/j.yfrne.2014.02.002. Epub 2014 Mar 4. PMID: 24607323; PMCID: PMC4096384.
32. Haaxma CA, Bloem BR, Borm GF, Oyen WJ, Leenders KL, Eshuis S, Booij J, Dluzen DE, Horstink MW. Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):819-24. doi: 10.1136/jnnp.2006.103788. Epub 2006 Nov 10. PMID: 17098842; PMCID: PMC2117736.
33. Cerri S, Mus L, Blandini F. Parkinson's Disease in Women and Men: What's the Difference? J Parkinsons Dis. 2019;9(3):501-515. doi: 10.3233/JPD-191683. PMID: 31282427; PMCID: PMC6700650.
34. Moisan F, Kab S, Mohamed F, Canonico M, Le Guern M, Quintin C, Carcaillon L, Nicolau J, Duport N, Singh-Manoux A, Boussac-Zarebska M, Elbaz A. Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):952-7. doi: 10.1136/jnnp-2015-312283. Epub 2015 Dec 23. PMID: 26701996; PMCID: PMC5013115.
35. Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J. Are men at greater risk for Parkinson's disease than women? J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):637-9. doi: 10.1136/jnnp.2003.020982. PMID: 15026515; PMCID: PMC1739032.
36. Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007 Jan 30;68(5):384-6. doi: 10.1212/01.wnl.0000247740.47667.03. Epub 2006 Nov 2. PMID: 17082464.
37. Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, Wang Z. Global Trends in the Incidence, Prevalence, and Years Lived With Disability of Parkinson's Disease in 204 Countries/Territories From 1990 to 2019. Front Public Health. 2021 Dec 7;9:776847. doi: 10.3389/fpubh.2021.776847. PMID: 34950630; PMCID: PMC8688697.
38. Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-S8. doi: 10.3233/JPD-181474. PMID: 30584159; PMCID: PMC6311367.
39. GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):939-953. doi: 10.1016/S1474-4422(18)30295-3. Epub 2018 Oct 1. Erratum in: Lancet Neurol. 2021 Dec;20(12):e7. PMID: 30287051; PMCID: PMC6191528.
40. Marras C, Beck JC, Bower JH, Roberts E, Ritz B, Ross GW, Abbott RD, Savica R, Van Den Eeden SK, Willis AW, Tanner CM; Parkinson’s Foundation P4 Group. Prevalence of Parkinson's disease across North America. NPJ Parkinsons Dis. 2018 Jul 10;4:21. doi: 10.1038/s41531-018-0058-0. PMID: 30003140; PMCID: PMC6039505.
41. Orozco JL, Valderrama-Chaparro JA, Pinilla-Monsalve GD, Molina-Echeverry MI, Pérez Castaño AM, Ariza-Araújo Y, Prada SI, Takeuchi Y. Parkinson's disease prevalence, age distribution and staging in Colombia. Neurol Int. 2020 Jul 10;12(1):8401. doi: 10.4081/ni.2020.8401. PMID: 32774822; PMCID: PMC7378539.
42. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The Incidence of Parkinson's Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2016;46(4):292-300. doi: 10.1159/000445751. Epub 2016 Apr 23. PMID: 27105081.
43. Ma CL, Su L, Xie JJ, Long JX, Wu P, Gu L. The prevalence and incidence of Parkinson's disease in China: a systematic review and meta-analysis. J Neural Transm (Vienna). 2014 Feb;121(2):123-34. doi: 10.1007/s00702-013-1092-z. Epub 2013 Sep 22. PMID: 24057652.
44. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM. Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003 Jun 1;157(11):1015-22. doi: 10.1093/aje/kwg068. PMID: 12777365.
45. Rocca WA. The burden of Parkinson's disease: a worldwide perspective. Lancet Neurol. 2018 Nov;17(11):928-929. doi: 10.1016/S1474-4422(18)30355-7. Epub 2018 Oct 1. PMID: 30287052.
46. Rizek P, Kumar N, Jog MS. An update on the diagnosis and treatment of Parkinson disease. CMAJ. 2016 Nov 1;188(16):1157-1165. doi: 10.1503/cmaj.151179. Epub 2016 May 24. PMID: 27221269; PMCID: PMC5088077.
47. DeMaagd G, Philip A. Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P T. 2015 Aug;40(8):504-32. PMID: 26236139; PMCID: PMC4517533.
48. Driver JA, Logroscino G, Gaziano JM, Kurth T. Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology. 2009 Feb 3;72(5):432-8. doi: 10.1212/01.wnl.0000341769.50075.bb. PMID: 19188574; PMCID: PMC2676726.
49. Frei K, Truong DD. Hallucinations and the spectrum of psychosis in Parkinson's disease. J Neurol Sci. 2017 Mar 15;374:56-62. doi: 10.1016/j.jns.2017.01.014. Epub 2017 Jan 5. PMID: 28108020.
50. Samudra N, Patel N, Womack KB, Khemani P, Chitnis S. Psychosis in Parkinson Disease: A Review of Etiology, Phenomenology, and Management. Drugs Aging. 2016 Dec;33(12):855-863. doi: 10.1007/s40266-016-0416-8. PMID: 27830568; PMCID: PMC6760850.
51. Chendo I, Fabbri M, Godinho C, Moiron Simões R, Severiano Sousa C, Coelho M, Voon V, Ferreira JJ. High frequency of psychosis in late-stage Parkinsońs disease. Clin Park Relat Disord. 2021 Nov 24;5:100119. doi: 10.1016/j.prdoa.2021.100119. PMID: 34988427; PMCID: PMC8710406.
52. Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005 Feb;20(2):190-9. doi: 10.1002/mds.20324. PMID: 15551331.
53. Ravina B, Marder K, Fernandez HH, Friedman JH, McDonald W, Murphy D, Aarsland D, Babcock D, Cummings J, Endicott J, Factor S, Galpern W, Lees A, Marsh L, Stacy M, Gwinn-Hardy K, Voon V, Goetz C. Diagnostic criteria for psychosis in Parkinson's disease: report of an NINDS, NIMH work group. Mov Disord. 2007 Jun 15;22(8):1061-8. doi: 10.1002/mds.21382. PMID: 17266092.
54. Garofalo S, Justicia A, Arrondo G, Ermakova AO, Ramachandra P, Tudor-Sfetea C, Robbins TW, Barker RA, Fletcher PC, Murray GK. Cortical and Striatal Reward Processing in Parkinson's Disease Psychosis. Front Neurol. 2017 Apr 24;8:156. doi: 10.3389/fneur.2017.00156. PMID: 28484422; PMCID: PMC5402044.
55. Toh WL, Yolland C, Gurvich C, Barnes J, Rossell SL. Non-visual hallucinations in Parkinson's disease: a systematic review. J Neurol. 2023 Jun;270(6):2857-2889. doi: 10.1007/s00415-022-11545-6. Epub 2023 Jan 27. PMID: 36702960; PMCID: PMC10188425.
56. Goetz CG, Stebbins GT, Ouyang B. Visual plus nonvisual hallucinations in Parkinson's disease: development and evolution over 10 years. Mov Disord. 2011 Oct;26(12):2196-200. doi: 10.1002/mds.23835. Epub 2011 Jul 13. PMID: 21755536.
57. Goldman JG, Vaughan CL, Goetz CG. An update expert opinion on management and research strategies in Parkinson's disease psychosis. Expert Opin Pharmacother. 2011 Sep;12(13):2009-24. doi: 10.1517/14656566.2011.587122. Epub 2011 Jun 2. PMID: 21635198; PMCID: PMC3152685.
58. Weil RS, Reeves S. Hallucinations in Parkinson's disease: new insights into mechanisms and treatments. Adv Clin Neurosci Rehabil. 2020 Jul 13;19(4):ONNS5189. doi: 10.47795/ONNS5189. PMID: 33102741; PMCID: PMC7116251.
59. Forsaa EB, Larsen JP, Wentzel-Larsen T, Goetz CG, Stebbins GT, Aarsland D, Alves G. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010 Aug;67(8):996-1001. doi: 10.1001/archneurol.2010.166. PMID: 20697051.
60. Lee AH, Weintraub D. Psychosis in Parkinson's disease without dementia: common and comorbid with other non-motor symptoms. Mov Disord. 2012 Jun;27(7):858-63. doi: 10.1002/mds.25003. Epub 2012 Jun 1. PMID: 22674352; PMCID: PMC3511789.
61. Korczyn AD. Hallucinations in Parkinson's disease. Lancet. 2001 Sep 29;358(9287):1031-2. doi: 10.1016/S0140-6736(01)06230-4. PMID: 11589931.
62. Williams-Gray CH, Foltynie T, Lewis SJ, Barker RA. Cognitive deficits and psychosis in Parkinson's disease: a review of pathophysiology and therapeutic options. CNS Drugs. 2006;20(6):477-505. doi: 10.2165/00023210-200620060-00004. PMID: 16734499.
63. Lokk J, Delbari A. Clinical aspects of palliative care in advanced Parkinson's disease. BMC Palliat Care. 2012 Oct 25;11:20. doi: 10.1186/1472-684X-11-20. PMID: 23098090; PMCID: PMC3528486.
64. Pham Nguyen TP, Abraham DS, Thibault D, Weintraub D, Willis AW. Low continuation of antipsychotic therapy in Parkinson disease - intolerance, ineffectiveness, or inertia? BMC Neurol. 2021 Jun 24;21(1):240. doi: 10.1186/s12883-021-02265-x. PMID: 34167473; PMCID: PMC8223332.
65. Schrag A, Hovris A, Morley D, Quinn N, Jahanshahi M. Caregiver-burden in parkinson's disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord. 2006 Jan;12(1):35-41. doi: 10.1016/j.parkreldis.2005.06.011. Epub 2005 Nov 3. PMID: 16271496.
66. Juneja A, Anand K, Chandra M, Deshpande S, Dhamija R, Kathuria P, Mahajan R. Neuropsychiatric Symptoms and Caregiver Burden in Parkinson's Disease. Ann Indian Acad Neurol. 2020 Sep-Oct;23(5):656-660. doi: 10.4103/aian.AIAN_91_20. Epub 2020 Jul 8. PMID: 33623267; PMCID: PMC7887493.
67. Chahine LM, Feldman R, Althouse A, Torsney B, Alzyoud L, Mantri S, Edison B, Albert S, Daeschler M, Kopil C, Marras C. Contribution of neuropsychiatric symptoms in Parkinson's disease to different domains of caregiver burden. J Neurol. 2021 Aug;268(8):2961-2972. doi: 10.1007/s00415-021-10443-7. Epub 2021 Feb 25. PMID: 33629181; PMCID: PMC8289810.
68. Nene D, Yadav R. Neuropsychiatric Symptoms and Caregiver Burden in Parkinson's Disease: Mitigating the Lack of Awareness! Ann Indian Acad Neurol. 2020 Jul-Aug;23(4):575-576. doi: 10.4103/aian.AIAN_301_20. Epub 2020 Jul 8. PMID: 33223690; PMCID: PMC7657276.
69. Tsai WC, Lin HC, Chang CC, Chang WN, Huang CC, Cheng KY, Wang HC, Lin WC, Hsiao SY, Lai YR, Lu CH, Tsai NW. Neuropsychiatric symptoms in Parkinson's disease: association with caregiver distress and disease severity. Int Psychogeriatr. 2020 Jun;32(6):733-739. doi: 10.1017/S1041610219001510. Epub 2019 Oct 24. PMID: 31647049.
70. Terum TM, Andersen JR, Rongve A, Aarsland D, Svendsboe EJ, Testad I. The relationship of specific items on the Neuropsychiatric Inventory to caregiver burden in dementia: a systematic review. Int J Geriatr Psychiatry. 2017 Jul;32(7):703-717. doi: 10.1002/gps.4704. Epub 2017 Mar 20. PMID: 28317166.
71. Steendam-Oldekamp E, Weerkamp N, Vonk JM, Bloem BR, van Laar T. Combined multidisciplinary in/outpatient rehabilitation delays definite nursing home admission in advanced Parkinson's disease patients. Front Neurol. 2023 Apr 13;14:1128891. doi: 10.3389/fneur.2023.1128891. PMID: 37122300; PMCID: PMC10133548.
72. Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study. J Am Geriatr Soc. 2000 Aug;48(8):938-42. doi: 10.1111/j.1532-5415.2000.tb06891.x. PMID: 10968298.
73. Eichel HV, Heine J, Wegner F, Rogozinski S, Stiel S, Groh A, Krey L, Höglinger GU, Klietz M. Neuropsychiatric Symptoms in Parkinson's Disease Patients Are Associated with Reduced Health-Related Quality of Life and Increased Caregiver Burden. Brain Sci. 2022 Jan 11;12(1):89. doi: 10.3390/brainsci12010089. PMID: 35053832; PMCID: PMC8774188.
74. Goetz CG, Stebbins GT. Mortality and hallucinations in nursing home patients with advanced Parkinson's disease. Neurology. 1995 Apr;45(4):669-71. doi: 10.1212/wnl.45.4.669. PMID: 7723953.
75. Gonzalez MC, Dalen I, Maple-Grødem J, Tysnes OB, Alves G. Parkinson's disease clinical milestones and mortality. NPJ Parkinsons Dis. 2022 May 12;8(1):58. doi: 10.1038/s41531-022-00320-z. PMID: 35550520; PMCID: PMC9098431.
76. Goetz CG, Wuu J, Curgian LM, Leurgans S. Hallucinations and sleep disorders in PD: six-year prospective longitudinal study. Neurology. 2005 Jan 11;64(1):81-6. doi: 10.1212/01.WNL.0000148479.10865.FE. PMID: 15642908.
77. Zahodne LB, Fernandez HH. Parkinson's psychosis. Curr Treat Options Neurol. 2010 May;12(3):200-11. doi: 10.1007/s11940-010-0072-y. PMID: 20842582; PMCID: PMC3045857.
78. Goetz CG, Ouyang B, Negron A, Stebbins GT. Hallucinations and sleep disorders in PD: ten-year prospective longitudinal study. Neurology. 2010 Nov 16;75(20):1773-9. doi: 10.1212/WNL.0b013e3181fd6158. Epub 2010 Oct 20. PMID: 20962287; PMCID: PMC2995381.
79. Goetz CG, Leurgans S, Pappert EJ, Raman R, Stemer AB. Prospective longitudinal assessment of hallucinations in Parkinson's disease. Neurology. 2001 Dec 11;57(11):2078-82. doi: 10.1212/wnl.57.11.2078. PMID: 11739829.
80. Taddei RN, Cankaya S, Dhaliwal S, Chaudhuri KR. Management of Psychosis in Parkinson's Disease: Emphasizing Clinical Subtypes and Pathophysiological Mechanisms of the Condition. Parkinsons Dis. 2017;2017:3256542. doi: 10.1155/2017/3256542. Epub 2017 Sep 12. PMID: 29104810; PMCID: PMC5613459.
81. Zahodne LB, Fernandez HH. Pathophysiology and treatment of psychosis in Parkinson's disease: a review. Drugs Aging. 2008;25(8):665-82. doi: 10.2165/00002512-200825080-00004. PMID: 18665659; PMCID: PMC3045853.
82. Zhang S, Ma Y. Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms. World J Psychiatry. 2022 Sep 19;12(9):1127-1140. doi: 10.5498/wjp.v12.i9.1127. PMID: 36186499; PMCID: PMC9521528.
83. Tost H, Alam T, Meyer-Lindenberg A. Dopamine and psychosis: theory, pathomechanisms and intermediate phenotypes. Neurosci Biobehav Rev. 2010 Apr;34(5):689-700. doi: 10.1016/j.neubiorev.2009.06.005. Epub 2009 Jun 24. PMID: 19559045; PMCID: PMC2838993.
84. Powell A, Ireland C, Lewis SJG. Visual Hallucinations and the Role of Medications in Parkinson's Disease: Triggers, Pathophysiology, and Management. J Neuropsychiatry Clin Neurosci. 2020 Fall;32(4):334-343. doi: 10.1176/appi.neuropsych.19110316. Epub 2020 May 6. PMID: 32374649.
85. Carmichael K, Sullivan B, Lopez E, Sun L, Cai H. Diverse midbrain dopaminergic neuron subtypes and implications for complex clinical symptoms of Parkinson's disease. Ageing Neurodegener Dis. 2021;1(4):10.20517/and.2021.07. doi: 10.20517/and.2021.07. Epub 2021 Jul 15. PMID: 34532720; PMCID: PMC8442626.
86. Rizzi G, Tan KR. Dopamine and Acetylcholine, a Circuit Point of View in Parkinson's Disease. Front Neural Circuits. 2017 Dec 22;11:110. doi: 10.3389/fncir.2017.00110. PMID: 29311846; PMCID: PMC5744635.
87. Caton M, Ochoa ELM, Barrantes FJ. The role of nicotinic cholinergic neurotransmission in delusional thinking. NPJ Schizophr. 2020 Jun 12;6(1):16. doi: 10.1038/s41537-020-0105-9. PMID: 32532978; PMCID: PMC7293341.
88. Scarr E, Gibbons AS, Neo J, Udawela M, Dean B. Cholinergic connectivity: it's implications for psychiatric disorders. Front Cell Neurosci. 2013 May 3;7:55. doi: 10.3389/fncel.2013.00055. PMID: 23653591; PMCID: PMC3642390.
89. Stang CD, Mullan AF, Camerucci E, Hajeb M, Turcano P, Martin P, Mielke MM, Josephs KA, Splett M, Abler V, Boeve BF, Bower JH, Savica R. Incidence, Prevalence, and Mortality of Psychosis Associated with Parkinson's Disease (1991-2010). J Parkinsons Dis. 2022;12(4):1319-1327. doi: 10.3233/JPD-213035. PMID: 35213389; PMCID: PMC9336204.
90. Mohammad ME, Vizcarra JA, Garcia X, Patel S, Margolius A, Yu XX, Fernandez HH. Impact of behavioral side effects on the management of Parkinson patients treated with dopamine agonists. Clin Park Relat Disord. 2021 Mar 2;4:100091. doi: 10.1016/j.prdoa.2021.100091. PMID: 34316669; PMCID: PMC8299972.
91. Cummings JL. Behavioral complications of drug treatment of Parkinson's disease. J Am Geriatr Soc. 1991 Jul;39(7):708-16. doi: 10.1111/j.1532-5415.1991.tb03627.x. PMID: 2061539.
92. Graham JM, Grünewald RA, Sagar HJ. Hallucinosis in idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1997 Oct;63(4):434-40. doi: 10.1136/jnnp.63.4.434. PMID: 9343119; PMCID: PMC2169767.
93. Inzelberg R, Kipervasser S, Korczyn AD. Auditory hallucinations in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):533-5. doi: 10.1136/jnnp.64.4.533. PMID: 9576549; PMCID: PMC2170055.
94. Aarsland D, Larsen JP, Cummins JL, Laake K. Prevalence and clinical correlates of psychotic symptoms in Parkinson disease: a community-based study. Arch Neurol. 1999 May;56(5):595-601. doi: 10.1001/archneur.56.5.595. PMID: 10328255.
95. Fénelon G, Mahieux F, Huon R, Ziégler M. Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors. Brain. 2000 Apr;123 ( Pt 4):733-45. doi: 10.1093/brain/123.4.733. PMID: 10734005.
96. Holroyd S, Currie L, Wooten GF. Prospective study of hallucinations and delusions in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2001 Jun;70(6):734-8. doi: 10.1136/jnnp.70.6.734. PMID: 11385005; PMCID: PMC1737419.
97. Schrag A, Ben-Shlomo Y, Quinn N. How common are complications of Parkinson's disease? J Neurol. 2002 Apr;249(4):419-23. doi: 10.1007/s004150200032. PMID: 11967646.
98. Marsh L, Williams JR, Rocco M, Grill S, Munro C, Dawson TM. Psychiatric comorbidities in patients with Parkinson disease and psychosis. Neurology. 2004 Jul 27;63(2):293-300. doi: 10.1212/01.wnl.0000129843.15756.a3. PMID: 15277623.
99. Merims D, Shabtai H, Korczyn AD, Peretz C, Weizman N, Giladi N. Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease. J Neural Transm (Vienna). 2004 Oct;111(10-11):1447-53. doi: 10.1007/s00702-004-0209-9. PMID: 15480845.
100. Paleacu D, Schechtman E, Inzelberg R. Association between family history of dementia and hallucinations in Parkinson disease. Neurology. 2005 May 24;64(10):1712-5. doi: 10.1212/01.WNL.0000161872.85903.8E. PMID: 15911796.
101. Meral H, Aydemir T, Ozer F, Ozturk O, Ozben S, Erol C, Cetin S, Hanoglu L, Ozkayran T, Yilsen M. Relationship between visual hallucinations and REM sleep behavior disorder in patients with Parkinson's disease. Clin Neurol Neurosurg. 2007 Dec;109(10):862-7. doi: 10.1016/j.clineuro.2007.08.010. PMID: 17913346.
102. Williams DR, Warren JD, Lees AJ. Using the presence of visual hallucinations to differentiate Parkinson's disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2008 Jun;79(6):652-5. doi: 10.1136/jnnp.2007.124677. Epub 2007 Sep 14. PMID: 17872984.
103. Papapetropoulos S, Katzen H, Schrag A, Singer C, Scanlon BK, Nation D, Guevara A, Levin B. A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease. BMC Neurol. 2008 Jun 20;8:21. doi: 10.1186/1471-2377-8-21. PMID: 18570642; PMCID: PMC2443167.
104. Fénelon G, Soulas T, Zenasni F, Cleret de Langavant L. The changing face of Parkinson's disease-associated psychosis: a cross-sectional study based on the new NINDS-NIMH criteria. Mov Disord. 2010 Apr 30;25(6):763-6. doi: 10.1002/mds.22839. PMID: 20437542; PMCID: PMC2891710.
105. Mack J, Rabins P, Anderson K, Goldstein S, Grill S, Hirsch ES, Lehmann S, Little JT, Margolis RL, Palanci J, Pontone G, Weiss H, Williams JR, Marsh L. Prevalence of psychotic symptoms in a community-based Parkinson disease sample. Am J Geriatr Psychiatry. 2012 Feb;20(2):123-32. doi: 10.1097/JGP.0b013e31821f1b41. PMID: 21617521; PMCID: PMC3168582.
106. Chou KL, Messing S, Oakes D, Feldman PD, Breier A, Friedman JH. Drug-induced psychosis in Parkinson disease: phenomenology and correlations among psychosis rating instruments. Clin Neuropharmacol. 2005 Sep-Oct;28(5):215-9. doi: 10.1097/01.wnf.0000180228.77802.32. PMID: 16239760.
107. Schrag A, Dodel R, Spottke A, Bornschein B, Siebert U, Quinn NP. Rate of clinical progression in Parkinson's disease. A prospective study. Mov Disord. 2007 May 15;22(7):938-45. doi: 10.1002/mds.21429. PMID: 17415791.
108. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008 Apr 30;23(6):837-44. doi: 10.1002/mds.21956. PMID: 18307261.
109. Biglan KM, Holloway RG Jr, McDermott MP, Richard IH; Parkinson Study Group CALM-PD Investigators. Risk factors for somnolence, edema, and hallucinations in early Parkinson disease. Neurology. 2007 Jul 10;69(2):187-95. doi: 10.1212/01.wnl.0000265593.34438.00. PMID: 17620552.
110. Mok VWL, Chan LG, Goh JCB, Tan LCS. Psychosis in Parkinson's disease in a Southeast Asian cohort: prevalence and clinical correlates. Singapore Med J. 2022 Dec;63(12):702-708. doi: 10.11622/smedj.2021182. Epub 2021 Dec 15. PMID: 34911181; PMCID: PMC9875879.
111. Williams DR, Lees AJ. Visual hallucinations in the diagnosis of idiopathic Parkinson's disease: a retrospective autopsy study. Lancet Neurol. 2005 Oct;4(10):605-10. doi: 10.1016/S1474-4422(05)70146-0. PMID: 16168928.
112. Fénelon G, Alves G. Epidemiology of psychosis in Parkinson's disease. J Neurol Sci. 2010 Feb 15;289(1-2):12-7. doi: 10.1016/j.jns.2009.08.014. Epub 2009 Sep 8. PMID: 19740486.
113. Ffytche DH, Pereira JB, Ballard C, Chaudhuri KR, Weintraub D, Aarsland D. Risk factors for early psychosis in PD: insights from the Parkinson's Progression Markers Initiative. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):325-331. doi: 10.1136/jnnp-2016-314832. PMID: 28315846; PMCID: PMC5362125.
114. Chaudhuri KR, Healy DG, Schapira AH; National Institute for Clinical Excellence. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006 Mar;5(3):235-45. doi: 10.1016/S1474-4422(06)70373-8. PMID: 16488379.
115. Factor SA, Feustel PJ, Friedman JH, Comella CL, Goetz CG, Kurlan R, Parsa M, Pfeiffer R; Parkinson Study Group. Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology. 2003 Jun 10;60(11):1756-61. doi: 10.1212/01.wnl.0000068010.82167.cf. PMID: 12796526.
116. Pappert EJ, Goetz CG, Niederman FG, Raman R, Leurgans S. Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson's disease. Mov Disord. 1999 Jan;14(1):117-21. doi: 10.1002/1531-8257(199901)14:1<117::aid-mds1019>3.0.co;2-0. PMID: 9918353.
117. Simonet C, Tolosa E, Camara A, Valldeoriola F. Emergencies and critical issues in Parkinson's disease. Pract Neurol. 2020 Feb;20(1):15-25. doi: 10.1136/practneurol-2018-002075. Epub 2019 Aug 19. PMID: 31427383; PMCID: PMC7029239.
118. Gama RL, de Bruin VM, de Bruin PF, Távora DG, Lopes EM, Jorge IF, Bittencourt LR, Tufik S. Risk factors for visual hallucinations in patients with Parkinson's disease. Neurol Res. 2015 Feb;37(2):112-6. doi: 10.1179/1743132814Y.0000000418. Epub 2014 Jul 8. PMID: 25002179.
119. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83. doi: 10.1001/jama.2014.3654. PMID: 24756517.
120. Fernandez HH, Aarsland D, Fénelon G, Friedman JH, Marsh L, Tröster AI, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. Scales to assess psychosis in Parkinson's disease: Critique and recommendations. Mov Disord. 2008 Mar 15;23(4):484-500. doi: 10.1002/mds.21875. PMID: 18175343.
121. Martinez-Ramirez D, Okun MS, Jaffee MS. Parkinson's disease psychosis: therapy tips and the importance of communication between neurologists and psychiatrists. Neurodegener Dis Manag. 2016 Aug;6(4):319-30. doi: 10.2217/nmt-2016-0009. Epub 2016 Jul 13. PMID: 27408981; PMCID: PMC5066136.
122. Thanvi BR, Lo TC, Harsh DP. Psychosis in Parkinson's disease. Postgrad Med J. 2005 Oct;81(960):644-6. doi: 10.1136/pgmj.2004.032029. PMID: 16210460; PMCID: PMC1743370.
123. Goetz CG, Wuu J, Curgian L, Leurgans S. Age-related influences on the clinical characteristics of new-onset hallucinations in Parkinson's disease patients. Mov Disord. 2006 Feb;21(2):267-70. doi: 10.1002/mds.20701. PMID: 16161144.
124. Amar BR, Yadav R, Janardhan Reddy YC, Pal PK. A clinical profile of patients with Parkinson's disease and psychosis. Ann Indian Acad Neurol. 2014 Apr;17(2):187-92. doi: 10.4103/0972-2327.132625. PMID: 25024570; PMCID: PMC4090845.
125. Chang A, Fox SH. Psychosis in Parkinson's Disease: Epidemiology, Pathophysiology, and Management. Drugs. 2016 Jul;76(11):1093-118. doi: 10.1007/s40265-016-0600-5. Erratum in: Drugs. 2016 Sep;76(13):1319. Dosage error in article text. PMID: 27312429.
126. Ffytche DH, Creese B, Politis M, Chaudhuri KR, Weintraub D, Ballard C, Aarsland D. The psychosis spectrum in Parkinson disease. Nat Rev Neurol. 2017 Feb;13(2):81-95. doi: 10.1038/nrneurol.2016.200. Epub 2017 Jan 20. PMID: 28106066; PMCID: PMC5656278.
127. Zhong J, Wu S, Zhao Y, Chen H, Zhao N, Zheng K, Zhao Z, Chen W, Wang B, Wu K. Why psychosis is frequently associated with Parkinson's disease? Neural Regen Res. 2013 Sep 25;8(27):2548-56. doi: 10.3969/j.issn.1673-5374.2013.27.006. PMID: 25206565; PMCID: PMC4145938.
128. Barnes J, David AS. Visual hallucinations in Parkinson's disease: a review and phenomenological survey. J Neurol Neurosurg Psychiatry. 2001 Jun;70(6):727-33. doi: 10.1136/jnnp.70.6.727. PMID: 11385004; PMCID: PMC1737396.
129. Vignando M, Ffytche D, Lewis SJG, Lee PH, Chung SJ, Weil RS, Hu MT, Mackay CE, Griffanti L, Pins D, Dujardin K, Jardri R, Taylor JP, Firbank M, McAlonan G, Mak HKF, Ho SL, Mehta MA. Author Correction: Mapping brain structural differences and neuroreceptor correlates in Parkinson's disease visual hallucinations. Nat Commun. 2022 Feb 15;13(1):971. doi: 10.1038/s41467-022-28491-6. Erratum for: Nat Commun. 2022 Jan 26;13(1):519. PMID: 35169136; PMCID: PMC8847348.
130. Mantovani E, Zucchella C, Argyriou AA, Tamburin S. Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson's disease: current evidence and future perspectives. Expert Rev Neurother. 2023 Jan;23(1):25-43. doi: 10.1080/14737175.2023.2173576. Epub 2023 Feb 9. PMID: 36701529.
131. Chendo I, Fabbri M, Godinho C, Moiron Simões R, Severiano Sousa C, Coelho M, Voon V, Ferreira JJ. High frequency of psychosis in late-stage Parkinsońs disease. Clin Park Relat Disord. 2021 Nov 24;5:100119. doi: 10.1016/j.prdoa.2021.100119. PMID: 34988427; PMCID: PMC8710406.
132. Pagonabarraga J, Martinez-Horta S, Fernández de Bobadilla R, Pérez J, Ribosa-Nogué R, Marín J, Pascual-Sedano B, García C, Gironell A, Kulisevsky J. Minor hallucinations occur in drug-naive Parkinson's disease patients, even from the premotor phase. Mov Disord. 2016 Jan;31(1):45-52. doi: 10.1002/mds.26432. Epub 2015 Sep 26. Erratum in: Mov Disord. 2016 Mar;31(3):433. PMID: 26408291.
133. Rana AQ, Siddiqui I, Zangeneh M, Fattah A, Awan N, Yousuf MS. Predicting treatment-seeking for visual hallucinations among Parkinson's disease patients. Psychiatry Clin Neurosci. 2013 Nov;67(7):509-16. doi: 10.1111/pcn.12083. Epub 2013 Sep 2. PMID: 23992392.
134. Llorca PM, Pereira B, Jardri R, Chereau-Boudet I, Brousse G, Misdrahi D, Fénelon G, Tronche AM, Schwan R, Lançon C, Marques A, Ulla M, Derost P, Debilly B, Durif F, de Chazeron I. Hallucinations in schizophrenia and Parkinson's disease: an analysis of sensory modalities involved and the repercussion on patients. Sci Rep. 2016 Dec 1;6:38152. doi: 10.1038/srep38152. PMID: 27905557; PMCID: PMC5131286.
135. Kulisevsky J, Pagonabarraga J, Pascual-Sedano B, García-Sánchez C, Gironell A; Trapecio Group Study. Prevalence and correlates of neuropsychiatric symptoms in Parkinson's disease without dementia. Mov Disord. 2008 Oct 15;23(13):1889-96. doi: 10.1002/mds.22246. PMID: 18709682.
136. Pacchetti C, Manni R, Zangaglia R, Mancini F, Marchioni E, Tassorelli C, Terzaghi M, Ossola M, Martignoni E, Moglia A, Nappi G. Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease. Mov Disord. 2005 Nov;20(11):1439-48. doi: 10.1002/mds.20582. PMID: 16028215.
137. Riedel O, Klotsche J, Spottke A, Deuschl G, Förstl H, Henn F, Heuser I, Oertel W, Reichmann H, Riederer P, Trenkwalder C, Dodel R, Wittchen HU. Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson's disease. J Neurol. 2010 Jul;257(7):1073-82. doi: 10.1007/s00415-010-5465-z. Epub 2010 Feb 6. PMID: 20140443.
138. Solla P, Cannas A, Ibba FC, Loi F, Corona M, Orofino G, Marrosu MG, Marrosu F. Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson's disease. J Neurol Sci. 2012 Dec 15;323(1-2):33-9. doi: 10.1016/j.jns.2012.07.026. Epub 2012 Aug 27. PMID: 22935408.
139. Verbaan D, van Rooden SM, Visser M, Marinus J, Emre M, van Hilten JJ. Psychotic and compulsive symptoms in Parkinson's disease. Mov Disord. 2009 Apr 15;24(5):738-44. doi: 10.1002/mds.22453. PMID: 19133665.
140. Naimark D, Jackson E, Rockwell E, Jeste DV. Psychotic symptoms in Parkinson's disease patients with dementia. J Am Geriatr Soc. 1996 Mar;44(3):296-9. doi: 10.1111/j.1532-5415.1996.tb00918.x. PMID: 8600200.
141. Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, Frades-Payo B, Agüera-Ortiz L, Weintraub D, Riesco A, Kurtis MM, Chaudhuri KR. Neuropsychiatric symptoms and caregiver's burden in Parkinson's disease. Parkinsonism Relat Disord. 2015 Jun;21(6):629-34. doi: 10.1016/j.parkreldis.2015.03.024. Epub 2015 Apr 9. PMID: 25892660.
142. Aarsland D, Brønnick K, Ehrt U, De Deyn PP, Tekin S, Emre M, Cummings JL. Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry. 2007 Jan;78(1):36-42. doi: 10.1136/jnnp.2005.083113. Epub 2006 Jul 4. PMID: 16820421; PMCID: PMC2117797.
143. Poletti M, Perugi G, Logi C, Romano A, Del Dotto P, Ceravolo R, Rossi G, Pepe P, Dell'Osso L, Bonuccelli U. Dopamine agonists and delusional jealousy in Parkinson's disease: a cross-sectional prevalence study. Mov Disord. 2012 Nov;27(13):1679-82. doi: 10.1002/mds.25129. Epub 2012 Nov 13. PMID: 23150469.
144. Roane DM, Rogers JD, Robinson JH, Feinberg TE. Delusional misidentification in association with parkinsonism. J Neuropsychiatry Clin Neurosci. 1998 Spring;10(2):194-8. doi: 10.1176/jnp.10.2.194. PMID: 9608408.
145. Stewart JT. Frégoli syndrome associated with levodopa treatment. Mov Disord. 2008 Jan 30;23(2):308-9. doi: 10.1002/mds.21843. PMID: 18044770.
146. Pagonabarraga J, Llebaria G, García-Sánchez C, Pascual-Sedano B, Gironell A, Kulisevsky J. A prospective study of delusional misidentification syndromes in Parkinson's disease with dementia. Mov Disord. 2008 Feb 15;23(3):443-8. doi: 10.1002/mds.21864. PMID: 18076112.
147. Goetz CG, Fan W, Leurgans S, Bernard B, Stebbins GT. The malignant course of "benign hallucinations" in Parkinson disease. Arch Neurol. 2006 May;63(5):713-6. doi: 10.1001/archneur.63.5.713. PMID: 16682540.
148. Goetz CG, Fan W, Leurgans S. Antipsychotic medication treatment for mild hallucinations in Parkinson's disease: Positive impact on long-term worsening. Mov Disord. 2008 Aug 15;23(11):1541-5. doi: 10.1002/mds.22132. PMID: 18567004.
149. Zhong M, Gu R, Zhu S, Bai Y, Wu Z, Jiang X, Shen B, Zhu J, Pan Y, Yan J, Zhang L. Prevalence and Risk Factors for Minor Hallucinations in Patients with Parkinson's Disease. Behav Neurol. 2021 Oct 4;2021:3469706. doi: 10.1155/2021/3469706. PMID: 34646400; PMCID: PMC8505047.
150. Factor SA, Scullin MK, Sollinger AB, Land JO, Wood-Siverio C, Zanders L, Freeman A, Bliwise DL, McDonald WM, Goldstein FC. Cognitive correlates of hallucinations and delusions in Parkinson's disease. J Neurol Sci. 2014 Dec 15;347(1-2):316-21. doi: 10.1016/j.jns.2014.10.033. Epub 2014 Oct 23. PMID: 25466695.
151. Factor SA, McDonald WM, Goldstein FC. The role of neurotransmitters in the development of Parkinson's disease-related psychosis. Eur J Neurol. 2017 Oct;24(10):1244-1254. doi: 10.1111/ene.13376. Epub 2017 Jul 31. PMID: 28758318.
152. Byrne P. Managing the acute psychotic episode. BMJ. 2007 Mar 31;334(7595):686-92. doi: 10.1136/bmj.39148.668160.80. PMID: 17395949; PMCID: PMC1839209.
153. Brendel RW, Stern TA. Psychotic symptoms in the elderly. Prim Care Companion J Clin Psychiatry. 2005;7(5):238-41. doi: 10.4088/pcc.v07n0506. PMID: 16308581; PMCID: PMC1257410.
154. Arciniegas DB. Psychosis. Continuum (Minneap Minn). 2015 Jun;21(3 Behavioral Neurology and Neuropsychiatry):715-36. doi: 10.1212/01.CON.0000466662.89908.e7. PMID: 26039850; PMCID: PMC4455840.
155. Sawada H, Oeda T, Yamamoto K, Umemura A, Tomita S, Hayashi R, Kohsaka M, Kawamura T. Trigger medications and patient-related risk factors for Parkinson disease psychosis requiring anti-psychotic drugs: a retrospective cohort study. BMC Neurol. 2013 Oct 12;13:145. doi: 10.1186/1471-2377-13-145. PMID: 24119306; PMCID: PMC3879653.
156. Poewe W. Psychosis in Parkinson's disease. Mov Disord. 2003 Sep;18 Suppl 6:S80-7. doi: 10.1002/mds.10567. PMID: 14502660.
157. Fénelon G. Psychosis in Parkinson's disease: phenomenology, frequency, risk factors, and current understanding of pathophysiologic mechanisms. CNS Spectr. 2008 Mar;13(3 Suppl 4):18-25. doi: 10.1017/s1092852900017284. PMID: 18323763.
158. Huse DM, Schulman K, Orsini L, Castelli-Haley J, Kennedy S, Lenhart G. Burden of illness in Parkinson's disease. Mov Disord. 2005 Nov;20(11):1449-54. doi: 10.1002/mds.20609. PMID: 16007641.
159. Keränen T, Kaakkola S, Sotaniemi K, Laulumaa V, Haapaniemi T, Jolma T, Kola H, Ylikoski A, Satomaa O, Kovanen J, Taimela E, Haapaniemi H, Turunen H, Takala A. Economic burden and quality of life impairment increase with severity of PD. Parkinsonism Relat Disord. 2003 Jan;9(3):163-8. doi: 10.1016/s1353-8020(02)00097-4. PMID: 12573872.
160. Johnson SJ, Kaltenboeck A, Diener M, Birnbaum HG, Grubb E, Castelli-Haley J, Siderowf AD. Costs of Parkinson's disease in a privately insured population. Pharmacoeconomics. 2013 Sep;31(9):799-806. doi: 10.1007/s40273-013-0075-0. PMID: 23907717; PMCID: PMC3757266.
161. Kaltenboeck A, Johnson SJ, Davis MR, Birnbaum HG, Carroll CA, Tarrants ML, Siderowf AD. Direct costs and survival of medicare beneficiaries with early and advanced Parkinson's disease. Parkinsonism Relat Disord. 2012 May;18(4):321-6. doi: 10.1016/j.parkreldis.2011.11.015. Epub 2011 Dec 16. PMID: 22177623.
162. Hermanowicz N, Edwards K. Parkinson's disease psychosis: symptoms, management, and economic burden. Am J Manag Care. 2015 Aug;21(10 Suppl):s199-206. PMID: 26296199.
163. Yang JX, Chen L. Economic Burden Analysis of Parkinson's Disease Patients in China. Parkinsons Dis. 2017;2017:8762939. doi: 10.1155/2017/8762939. Epub 2017 Jun 14. PMID: 28695039; PMCID: PMC5488490.
164. Goetz CG, Stebbins GT. Risk factors for nursing home placement in advanced Parkinson's disease. Neurology. 1993 Nov;43(11):2227-9. doi: 10.1212/wnl.43.11.2227. PMID: 8232934.
165. Wolters EC. Dopaminomimetic psychosis in Parkinson's disease patients: diagnosis and treatment. Neurology. 1999;52(7 Suppl 3):S10-3. PMID: 10227604.
166. Stahl SM. Parkinson's disease psychosis as a serotonin-dopamine imbalance syndrome. CNS Spectr. 2016 Oct;21(5):355-359. doi: 10.1017/S1092852916000602. PMID: 27686027.
167. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain. 2002 Feb;125(Pt 2):391-403. doi: 10.1093/brain/awf033. PMID: 11844739.
168. Birkmayer W, Riederer P. Responsibility of extrastriatal areas for the appearance of psychotic symptoms (clinical and biochemical human post-mortem findings). J Neural Transm. 1975;37(2):175-82. doi: 10.1007/BF01663632. PMID: 1185162.
169. Glennon RA, Titeler M, McKenney JD. Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci. 1984 Dec 17;35(25):2505-11. doi: 10.1016/0024-3205(84)90436-3. PMID: 6513725.
170. Titeler M, Lyon RA, Glennon RA. Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology (Berl). 1988;94(2):213-6. doi: 10.1007/BF00176847. PMID: 3127847.
171. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry. 2001 Mar;158(3):360-9. doi: 10.1176/appi.ajp.158.3.360. PMID: 11229973.
172. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. PMID: 11873706.
173. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther. 1989 Oct;251(1):238-46. PMID: 2571717.
174. Ballanger B, Strafella AP, van Eimeren T, Zurowski M, Rusjan PM, Houle S, Fox SH. Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol. 2010 Apr;67(4):416-21. doi: 10.1001/archneurol.2010.35. PMID: 20385906.
175. Huot P, Johnston TH, Darr T, Hazrati LN, Visanji NP, Pires D, Brotchie JM, Fox SH. Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations. Mov Disord. 2010 Jul 30;25(10):1399-408. doi: 10.1002/mds.23083. PMID: 20629135.
176. Grosch J, Winkler J, Kohl Z. Early Degeneration of Both Dopaminergic and Serotonergic Axons - A Common Mechanism in Parkinson's Disease. Front Cell Neurosci. 2016 Dec 22;10:293. doi: 10.3389/fncel.2016.00293. PMID: 28066188; PMCID: PMC5177648.
177. Politis M, Loane C. Serotonergic dysfunction in Parkinson's disease and its relevance to disability. ScientificWorldJournal. 2011;11:1726-34. doi: 10.1100/2011/172893. Epub 2011 Oct 17. PMID: 22125431; PMCID: PMC3201695.
178. Qamhawi Z, Towey D, Shah B, Pagano G, Seibyl J, Marek K, Borghammer P, Brooks DJ, Pavese N. Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease. Brain. 2015 Oct;138(Pt 10):2964-73. doi: 10.1093/brain/awv215. Epub 2015 Jul 23. PMID: 26209314.
179. Zhu K, van Hilten JJ, Putter H, Marinus J. Risk factors for hallucinations in Parkinson's disease: results from a large prospective cohort study. Mov Disord. 2013 Jun;28(6):755-62. doi: 10.1002/mds.25389. Epub 2013 Mar 20. PMID: 23520046.
180. Giladi N, Treves TA, Paleacu D, Shabtai H, Orlov Y, Kandinov B, Simon ES, Korczyn AD. Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease. J Neural Transm (Vienna). 2000;107(1):59-71. doi: 10.1007/s007020050005. PMID: 10809404.
181. Gallagher DA, Schrag A. Psychosis, apathy, depression and anxiety in Parkinson's disease. Neurobiol Dis. 2012 Jun;46(3):581-9. doi: 10.1016/j.nbd.2011.12.041. Epub 2012 Jan 3. PMID: 22245219.
182. Han JW, Ahn YD, Kim WS, Shin CM, Jeong SJ, Song YS, Bae YJ, Kim JM. Psychiatric Manifestation in Patients with Parkinson's Disease. J Korean Med Sci. 2018 Nov 1;33(47):e300. doi: 10.3346/jkms.2018.33.e300. PMID: 30450025; PMCID: PMC6236081.
183. Dujardin K, Sgambato V. Neuropsychiatric Disorders in Parkinson's Disease: What Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems? Front Neurosci. 2020 Jan 29;14:25. doi: 10.3389/fnins.2020.00025. PMID: 32063833; PMCID: PMC7000525.
184. Thanvi BR, Munshi SK, Vijaykumar N, Lo TC. Neuropsychiatric non-motor aspects of Parkinson's disease. Postgrad Med J. 2003 Oct;79(936):561-5. doi: 10.1136/pmj.79.936.561. PMID: 14612597; PMCID: PMC1742855.
185. Russo M, Carrarini C, Dono F, Rispoli MG, Di Pietro M, Di Stefano V, Ferri L, Bonanni L, Sensi SL, Onofrj M. The Pharmacology of Visual Hallucinations in Synucleinopathies. Front Pharmacol. 2019 Dec 9;10:1379. doi: 10.3389/fphar.2019.01379. PMID: 31920635; PMCID: PMC6913661.
186. Kurita A, Koshikawa H, Akiba T, Seki K, Ishikawa H, Suzuki M. Visual Hallucinations and Impaired Conscious Visual Perception in Parkinson Disease. J Geriatr Psychiatry Neurol. 2020 Nov;33(6):377-385. doi: 10.1177/0891988719892318. Epub 2019 Dec 6. PMID: 31808354.
187. Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9730467. doi: 10.1155/2016/9730467. Epub 2015 Dec 6. PMID: 26770661; PMCID: PMC4684895.
188. Sulzer D, Cragg SJ, Rice ME. Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia. 2016 Aug;6(3):123-148. doi: 10.1016/j.baga.2016.02.001. PMID: 27141430; PMCID: PMC4850498.
189. Ranjbar-Slamloo Y, Fazlali Z. Dopamine and Noradrenaline in the Brain; Overlapping or Dissociate Functions? Front Mol Neurosci. 2020 Jan 21;12:334. doi: 10.3389/fnmol.2019.00334. PMID: 32038164; PMCID: PMC6986277.
190. Jackson ME, Moghaddam B. Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex. J Neurosci. 2001 Jan 15;21(2):676-81. doi: 10.1523/JNEUROSCI.21-02-00676.2001. PMID: 11160446; PMCID: PMC6763812.
191. Goldman JG. New thoughts on thought disorders in Parkinson's disease: review of current research strategies and challenges. Parkinsons Dis. 2011 Mar 2;2011:675630. doi: 10.4061/2011/675630. PMID: 21403865; PMCID: PMC3049364.
192. Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J, Bogerts B, Braun K, Jankowski Z, Kumaratilake J, Henneberg M, Gos T. The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry. 2014 May 19;5:47. doi: 10.3389/fpsyt.2014.00047. Erratum in: Front Psychiatry. 2014;5:110. Braun, Anna Katharina [corrected to Braun, Katharina]; Kumaritlake, Jaliya [corrected to Kumaratilake, Jaliya]. PMID: 24904434; PMCID: PMC4032934.
193. Li P, Snyder GL, Vanover KE. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future. Curr Top Med Chem. 2016;16(29):3385-3403. doi: 10.2174/1568026616666160608084834. PMID: 27291902; PMCID: PMC5112764.
194. Ecker D, Unrath A, Kassubek J, Sabolek M. Dopamine Agonists and their risk to induce psychotic episodes in Parkinson's disease: a case-control study. BMC Neurol. 2009 Jun 10;9:23. doi: 10.1186/1471-2377-9-23. PMID: 19515253; PMCID: PMC2704166.
195. Carta M, Carlsson T, Kirik D, Björklund A. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain. 2007 Jul;130(Pt 7):1819-33. doi: 10.1093/brain/awm082. Epub 2007 Apr 23. PMID: 17452372.
196. Laprade N, Radja F, Reader TA, Soghomonian JJ. Dopamine receptor agonists regulate levels of the serotonin 5-HT2A receptor and its mRNA in a subpopulation of rat striatal neurons. J Neurosci. 1996 Jun 1;16(11):3727-36. doi: 10.1523/JNEUROSCI.16-11-03727.1996. PMID: 8642415; PMCID: PMC6578831.
197. Radja F, Descarries L, Dewar KM, Reader TA. Serotonin 5-HT1 and 5-HT2 receptors in adult rat brain after neonatal destruction of nigrostriatal dopamine neurons: a quantitative autoradiographic study. Brain Res. 1993 Mar 26;606(2):273-85. doi: 10.1016/0006-8993(93)90995-y. PMID: 8490720.
198. Nausieda PA, Tanner CM, Klawans HL. Serotonergically active agents in levodopa-induced psychiatric toxicity reactions. Adv Neurol. 1983;37:23-32. PMID: 6858774.
199. Weintraub D, Hurtig HI. Presentation and management of psychosis in Parkinson's disease and dementia with Lewy bodies. Am J Psychiatry. 2007 Oct;164(10):1491-8. doi: 10.1176/appi.ajp.2007.07040715. PMID: 17898337; PMCID: PMC2137166.
200. Camicioli R, Fisher N. Progress in clinical neurosciences: Parkinson's disease with dementia and dementia with Lewy bodies. Can J Neurol Sci. 2004 Feb;31(1):7-21. doi: 10.1017/s0317167100002791. PMID: 15038467.
201. Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999 Jun;22(6):273-80. doi: 10.1016/s0166-2236(98)01361-7. PMID: 10354606.
202. Chen JJ. Treatment of psychotic symptoms in patients with Parkinson disease. Ment Health Clin. 2018 Mar 23;7(6):262-270. doi: 10.9740/mhc.2017.11.262. PMID: 29955532; PMCID: PMC6007727.
203. Burn D, Emre M, McKeith I, De Deyn PP, Aarsland D, Hsu C, Lane R. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord. 2006 Nov;21(11):1899-907. doi: 10.1002/mds.21077. PMID: 16960863.
204. Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev. 2012 Mar 14;2012(3):CD006504. doi: 10.1002/14651858.CD006504.pub2. PMID: 22419314; PMCID: PMC8985413.
205. Perry EK, Perry RH. Acetylcholine and hallucinations: disease-related compared to drug-induced alterations in human consciousness. Brain Cogn. 1995 Aug;28(3):240-58. doi: 10.1006/brcg.1995.1255. PMID: 8546852.
206. Bosboom JL, Stoffers D, Wolters ECh. The role of acetylcholine and dopamine in dementia and psychosis in Parkinson's disease. J Neural Transm Suppl. 2003;(65):185-95. doi: 10.1007/978-3-7091-0643-3_11. PMID: 12946056.
207. Perry EK, Irving D, Kerwin JM, McKeith IG, Thompson P, Collerton D, Fairbairn AF, Ince PG, Morris CM, Cheng AV, et al. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease. Alzheimer Dis Assoc Disord. 1993 Summer;7(2):69-79. doi: 10.1097/00002093-199307020-00002. PMID: 8347330.
208. Fioravanti V, Benuzzi F, Codeluppi L, Contardi S, Cavallieri F, Nichelli P, Valzania F. MRI correlates of Parkinson's disease progression: a voxel based morphometry study. Parkinsons Dis. 2015;2015:378032. doi: 10.1155/2015/378032. Epub 2015 Jan 6. PMID: 25628916; PMCID: PMC4299788.
209. Riederer P, Lange KW, Kornhuber J, Danielczyk W. Glutamatergic-dopaminergic balance in the brain. Its importance in motor disorders and schizophrenia. Arzneimittelforschung. 1992 Feb;42(2A):265-8. PMID: 1350197.
210. Zhang Z, Zhang S, Fu P, Zhang Z, Lin K, Ko JK, Yung KK. Roles of Glutamate Receptors in Parkinson's Disease. Int J Mol Sci. 2019 Sep 6;20(18):4391. doi: 10.3390/ijms20184391. PMID: 31500132; PMCID: PMC6769661.
211. Pagonabarraga J, Tinazzi M, Caccia C, Jost WH. The role of glutamatergic neurotransmission in the motor and non-motor symptoms in Parkinson's disease: Clinical cases and a review of the literature. J Clin Neurosci. 2021 Aug;90:178-183. doi: 10.1016/j.jocn.2021.05.056. Epub 2021 Jun 10. PMID: 34275546.
212. Rodríguez-Violante M, Cervantes-Arriaga A, González-Latapí P, León-Ortiz P, de la Fuente-Sandoval C, Corona T. Proton Magnetic Resonance Spectroscopy Changes in Parkinson's Disease With and Without Psychosis. Rev Invest Clin. 2015 Jul-Aug;67(4):227-34. PMID: 26426588.
213. Lenka A, Ingalhalikar M, Shah A, Saini J, Arumugham SS, Hegde S, George L, Reddy V, Reddy YCJ, Yadav R, Pal PK. Hippocampal subfield atrophy in patients with Parkinson's disease and psychosis. J Neural Transm (Vienna). 2018 Sep;125(9):1361-1372. doi: 10.1007/s00702-018-1891-3. Epub 2018 Jun 1. PMID: 29858658; PMCID: PMC7613147.
214. Jacobson SA, Morshed T, Dugger BN, Beach TG, Hentz JG, Adler CH, Shill HA, Sabbagh MN, Belden CM, Sue LI, Caviness JN, Hu C; Arizona Parkinson's Disease Consortium. Plaques and tangles as well as Lewy-type alpha synucleinopathy are associated with formed visual hallucinations. Parkinsonism Relat Disord. 2014 Sep;20(9):1009-14. doi: 10.1016/j.parkreldis.2014.06.018. Epub 2014 Jun 28. PMID: 25027359; PMCID: PMC4143433.
215. Lenka A, Ingalhalikar M, Shah A, Saini J, Arumugham SS, Hegde S, George L, Yadav R, Pal PK. Abnormalities in the white matter tracts in patients with Parkinson disease and psychosis. Neurology. 2020 May 5;94(18):e1876-e1884. doi: 10.1212/WNL.0000000000009363. Epub 2020 Apr 21. PMID: 32317347; PMCID: PMC7613151.
216. Fox SH, Visanji NP, Johnston TH, Gomez-Ramirez J, Voon V, Brotchie JM. Dopamine receptor agonists and levodopa and inducing psychosis-like behavior in the MPTP primate model of Parkinson disease. Arch Neurol. 2006 Sep;63(9):1343-4. doi: 10.1001/archneur.63.9.1343. PMID: 16966523.
217. Goetz CG, Pappert EJ, Blasucci LM, Stebbins GT, Ling ZD, Nora MV, Carvey PM. Intravenous levodopa in hallucinating Parkinson's disease patients: high-dose challenge does not precipitate hallucinations. Neurology. 1998 Feb;50(2):515-7. doi: 10.1212/wnl.50.2.515. PMID: 9484386.
218. Dotchin CL, Jusabani A, Walker RW. Non-motor symptoms in a prevalent population with Parkinson's disease in Tanzania. Parkinsonism Relat Disord. 2009 Jul;15(6):457-60. doi: 10.1016/j.parkreldis.2008.11.013. Epub 2009 Feb 3. PMID: 19196538.
219. de la Riva P, Smith K, Xie SX, Weintraub D. Course of psychiatric symptoms and global cognition in early Parkinson disease. Neurology. 2014 Sep 16;83(12):1096-103. doi: 10.1212/WNL.0000000000000801. Epub 2014 Aug 15. PMID: 25128183; PMCID: PMC4166362.
220. Weintraub D, Simuni T, Caspell-Garcia C, Coffey C, Lasch S, Siderowf A, Aarsland D, Barone P, Burn D, Chahine LM, Eberling J, Espay AJ, Foster ED, Leverenz JB, Litvan I, Richard I, Troyer MD, Hawkins KA; Parkinson's Progression Markers Initiative. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease. Mov Disord. 2015 Jun;30(7):919-27. doi: 10.1002/mds.26170. Epub 2015 Mar 4. PMID: 25737166; PMCID: PMC4855523.
221. Goetz CG, Tanner CM, Klawans HL. Pharmacology of hallucinations induced by long-term drug therapy. Am J Psychiatry. 1982 Apr;139(4):494-7. doi: 10.1176/ajp.139.4.494. PMID: 6802003.
222. Hisahara S, Shimohama S. Dopamine receptors and Parkinson's disease. Int J Med Chem. 2011;2011:403039. doi: 10.1155/2011/403039. Epub 2011 Jun 13. PMID: 25954517; PMCID: PMC4411877.
223. Moskovitz C, Moses H 3rd, Klawans HL. Levodopa-induced psychosis: a kindling phenomenon. Am J Psychiatry. 1978 Jun;135(6):669-75. doi: 10.1176/ajp.135.6.669. PMID: 655276.
224. Sokoloff P, Diaz J, Le Foll B, Guillin O, Leriche L, Bezard E, Gross C. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets. 2006 Feb;5(1):25-43. doi: 10.2174/187152706784111551. PMID: 16613552.
225. Rondou P, Haegeman G, Van Craenenbroeck K. The dopamine D4 receptor: biochemical and signalling properties. Cell Mol Life Sci. 2010 Jun;67(12):1971-86. doi: 10.1007/s00018-010-0293-y. Epub 2010 Feb 18. PMID: 20165900.
226. Schwartz JC, Diaz J, Pilon C, Sokoloff P. Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions. Brain Res Brain Res Rev. 2000 Mar;31(2-3):277-87. doi: 10.1016/s0165-0173(99)00043-0. PMID: 10719154.
227. Maramai S, Gemma S, Brogi S, Campiani G, Butini S, Stark H, Brindisi M. Dopamine D3 Receptor Antagonists as Potential Therapeutics for the Treatment of Neurological Diseases. Front Neurosci. 2016 Oct 5;10:451. doi: 10.3389/fnins.2016.00451. PMID: 27761108; PMCID: PMC5050208.
228. Gurevich EV, Joyce JN. Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons. Neuropsychopharmacology. 1999 Jan;20(1):60-80. doi: 10.1016/S0893-133X(98)00066-9. PMID: 9885786.
229. Guma E, Rocchetti J, Devenyi GA, Tanti A, Mathieu AP, Lerch JP, Elgbeili G, Courcot B, Mechawar N, Chakravarty MM, Giros B. Role of D3 dopamine receptors in modulating neuroanatomical changes in response to antipsychotic administration. Sci Rep. 2019 May 24;9(1):7850. doi: 10.1038/s41598-019-43955-4. PMID: 31127135; PMCID: PMC6534671.
230. Yang P, Perlmutter JS, Benzinger TLS, Morris JC, Xu J. Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment? Ageing Res Rev. 2020 Jan;57:100994. doi: 10.1016/j.arr.2019.100994. Epub 2019 Nov 22. PMID: 31765822; PMCID: PMC6939386.
231. Bono F, Mutti V, Fiorentini C, Missale C. Dopamine D3 Receptor Heteromerization: Implications for Neuroplasticity and Neuroprotection. Biomolecules. 2020 Jul 9;10(7):1016. doi: 10.3390/biom10071016. PMID: 32659920; PMCID: PMC7407647.
232. Rossi M, Fasciani I, Marampon F, Maggio R, Scarselli M. The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs. Mol Pharmacol. 2017 Jun;91(6):586-594. doi: 10.1124/mol.116.107607. Epub 2017 Mar 6. PMID: 28265019; PMCID: PMC5438131.
233. Glickstein SB, Desteno DA, Hof PR, Schmauss C. Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention. Cereb Cortex. 2005 Jul;15(7):1016-24. doi: 10.1093/cercor/bhh202. Epub 2004 Nov 10. PMID: 15537671.
234. Sun J, Cairns NJ, Perlmutter JS, Mach RH, Xu J. Regulation of dopamine D₃ receptor in the striatal regions and substantia nigra in diffuse Lewy body disease. Neuroscience. 2013 Sep 17;248:112-26. doi: 10.1016/j.neuroscience.2013.05.048. Epub 2013 Jun 1. PMID: 23732230; PMCID: PMC3796121.
235. Gomperts SN. Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia. Continuum (Minneap Minn). 2016 Apr;22(2 Dementia):435-63. doi: 10.1212/CON.0000000000000309. PMID: 27042903; PMCID: PMC5390937.
236. Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson's disease dementia the same disease? BMC Med. 2018 Mar 6;16(1):34. doi: 10.1186/s12916-018-1016-8. PMID: 29510692; PMCID: PMC5840831.
237. Hepp DH, Ruiter AM, Galis Y, Voorn P, Rozemuller AJ, Berendse HW, Foncke EM, van de Berg WD. Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients. J Neuropathol Exp Neurol. 2013 Dec;72(12):1162-70. doi: 10.1097/NEN.0000000000000014. PMID: 24226265.
238. Gallagher DA, Parkkinen L, O'Sullivan SS, Spratt A, Shah A, Davey CC, Bremner FD, Revesz T, Williams DR, Lees AJ, Schrag A. Testing an aetiological model of visual hallucinations in Parkinson's disease. Brain. 2011 Nov;134(Pt 11):3299-309. doi: 10.1093/brain/awr225. Epub 2011 Sep 15. PMID: 21921019.
239. Fischer NM, Hinkle JT, Perepezko K, Bakker CC, Morris M, Broen MPG, Butala A, Dawson TM, Leentjens AFG, Mari Z, Marvel CL, Mills KA, Rosenthal LS, Shepard MD, Pantelyat A, Bakker A, Pletnikova O, Troncoso JC, Wang J, Pontone GM. Brainstem Pathologies Correlate With Depression and Psychosis in Parkinson's Disease. Am J Geriatr Psychiatry. 2021 Sep;29(9):958-968. doi: 10.1016/j.jagp.2020.12.009. Epub 2021 Jan 15. PMID: 33455856; PMCID: PMC8277871.
240. Arnulf I, Bonnet AM, Damier P, Bejjani BP, Seilhean D, Derenne JP, Agid Y. Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis. Neurology. 2000 Jul 25;55(2):281-8. doi: 10.1212/wnl.55.2.281. PMID: 10908906.
241. Barnes J, Boubert L, Harris J, Lee A, David AS. Reality monitoring and visual hallucinations in Parkinson's disease. Neuropsychologia. 2003;41(5):565-74. doi: 10.1016/s0028-3932(02)00182-3. PMID: 12559149.
242. Diederich NJ, Goetz CG, Stebbins GT. Repeated visual hallucinations in Parkinson's disease as disturbed external/internal perceptions: focused review and a new integrative model. Mov Disord. 2005 Feb;20(2):130-40. doi: 10.1002/mds.20308. PMID: 15486924.
243. Grossi D, Trojano L, Pellecchia MT, Amboni M, Fragassi NA, Barone P. Frontal dysfunction contributes to the genesis of hallucinations in non-demented Parkinsonian patients. Int J Geriatr Psychiatry. 2005 Jul;20(7):668-73. doi: 10.1002/gps.1339. PMID: 16021658.
244. Shine JM, Halliday GM, Naismith SL, Lewis SJ. Visual misperceptions and hallucinations in Parkinson's disease: dysfunction of attentional control networks? Mov Disord. 2011 Oct;26(12):2154-9. doi: 10.1002/mds.23896. Epub 2011 Sep 23. PMID: 21953814.
245. Stebbins GT, Goetz CG, Carrillo MC, Bangen KJ, Turner DA, Glover GH, Gabrieli JD. Altered cortical visual processing in PD with hallucinations: an fMRI study. Neurology. 2004 Oct 26;63(8):1409-16. doi: 10.1212/01.wnl.0000141853.27081.bd. PMID: 15505157.
246. Meppelink AM, de Jong BM, Renken R, Leenders KL, Cornelissen FW, van Laar T. Impaired visual processing preceding image recognition in Parkinson's disease patients with visual hallucinations. Brain. 2009 Nov;132(Pt 11):2980-93. doi: 10.1093/brain/awp223. Epub 2009 Sep 15. PMID: 19755518.
247. Straughan S, Collerton D, Bruce V. Visual Priming and Visual Hallucinations in Parkinson's Disease. Evidence for Normal Top-Down Processes. J Geriatr Psychiatry Neurol. 2016 Jan;29(1):25-30. doi: 10.1177/0891988715598237. Epub 2015 Jul 30. PMID: 26232406.
248. Firbank MJ, Parikh J, Murphy N, Killen A, Allan CL, Collerton D, Blamire AM, Taylor JP. Reduced occipital GABA in Parkinson disease with visual hallucinations. Neurology. 2018 Aug 14;91(7):e675-e685. doi: 10.1212/WNL.0000000000006007. Epub 2018 Jul 18. PMID: 30021920; PMCID: PMC6105043.
249. Bejr-Kasem H, Sampedro F, Marín-Lahoz J, Martínez-Horta S, Pagonabarraga J, Kulisevsky J. Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease. Eur J Neurol. 2021 Feb;28(2):438-447. doi: 10.1111/ene.14576. Epub 2020 Nov 5. PMID: 33032389.
250. Goldman JG, Stebbins GT, Dinh V, Bernard B, Merkitch D, deToledo-Morrell L, Goetz CG. Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson's disease with hallucinations. Brain. 2014 Mar;137(Pt 3):849-59. doi: 10.1093/brain/awt360. Epub 2014 Jan 29. PMID: 24480486; PMCID: PMC3983409.
251. Zarkali A, McColgan P, Leyland LA, Lees AJ, Rees G, Weil RS. Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction. Neurology. 2020 Apr 7;94(14):e1525-e1538. doi: 10.1212/WNL.0000000000009014. Epub 2020 Feb 24. PMID: 32094242; PMCID: PMC7251523.
252. Chen CC, Lee ST, Wu T, Chen CJ, Chen MC, Lu CS. Short-term effect of bilateral subthalamic stimulation for advanced Parkinson's disease. Chang Gung Med J. 2003 May;26(5):344-51. PMID: 12934851.
253. Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, Bhatia KP, Quinn N. Parkin disease: a phenotypic study of a large case series. Brain. 2003 Jun;126(Pt 6):1279-92. doi: 10.1093/brain/awg142. PMID: 12764051.
254. Lohmann E, Thobois S, Lesage S, Broussolle E, du Montcel ST, Ribeiro MJ, Remy P, Pelissolo A, Dubois B, Mallet L, Pollak P, Agid Y, Brice A; French Parkinson's Disease Genetics Study Group. A multidisciplinary study of patients with early-onset PD with and without parkin mutations. Neurology. 2009 Jan 13;72(2):110-6. doi: 10.1212/01.wnl.0000327098.86861.d4. Epub 2008 Nov 5. PMID: 18987353; PMCID: PMC2677494.
255. Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, Nishioka K, Fuchs J, Gasser T, Maraganore DM, Adler CH, Larvor L, Chartier-Harlin MC, Nilsson C, Langston JW, Gwinn K, Hattori N, Farrer MJ. Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann Neurol. 2008 Jun;63(6):743-50. doi: 10.1002/ana.21380. PMID: 18571778; PMCID: PMC3850281.
256. Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, Imai H, Kitami T, Sato K, Kuroda R, Tomiyama H, Mizoguchi K, Murata M, Toda T, Imoto I, Inazawa J, Mizuno Y, Hattori N. Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease. Ann Neurol. 2006 Feb;59(2):298-309. doi: 10.1002/ana.20753. PMID: 16358335.
257. Oeda T, Umemura A, Mori Y, Tomita S, Kohsaka M, Park K, Inoue K, Fujimura H, Hasegawa H, Sugiyama H, Sawada H. Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease. Neurobiol Aging. 2015 Dec;36(12):3306-3313. doi: 10.1016/j.neurobiolaging.2015.08.027. Epub 2015 Sep 7. PMID: 26422360.
258. Lenka A, Arumugham SS, Christopher R, Pal PK. Genetic substrates of psychosis in patients with Parkinson's disease: A critical review. J Neurol Sci. 2016 May 15;364:33-41. doi: 10.1016/j.jns.2016.03.005. Epub 2016 Mar 3. PMID: 27084212.
259. Ojo OO, Fernandez HH. Current Understanding of Psychosis in Parkinson's Disease. Curr Psychiatry Rep. 2016 Oct;18(10):97. doi: 10.1007/s11920-016-0730-1. PMID: 27629356.
260. de la Fuente-Fernández R, Núñez MA, López E. The apolipoprotein E epsilon 4 allele increases the risk of drug-induced hallucinations in Parkinson's disease. Clin Neuropharmacol. 1999 Jul-Aug;22(4):226-30. PMID: 10442253.
261. Factor SA, Steenland NK, Higgins DS, Molho ES, Kay DM, Montimurro J, Rosen AR, Zabetian CP, Payami H. Disease-related and genetic correlates of psychotic symptoms in Parkinson's disease. Mov Disord. 2011 Oct;26(12):2190-5. doi: 10.1002/mds.23806. Epub 2011 Jun 28. PMID: 21714002; PMCID: PMC4216677.
262. Goetz CG, Burke PF, Leurgans S, Berry-Kravis E, Blasucci LM, Raman R, Zhou L. Genetic variation analysis in parkinson disease patients with and without hallucinations: case-control study. Arch Neurol. 2001 Feb;58(2):209-13. doi: 10.1001/archneur.58.2.209. PMID: 11176958.
263. Camicioli R, Rajput A, Rajput M, Reece C, Payami H, Hao C, Rajput A. Apolipoprotein E epsilon4 and catechol-O-methyltransferase alleles in autopsy-proven Parkinson's disease: relationship to dementia and hallucinations. Mov Disord. 2005 Aug;20(8):989-94. doi: 10.1002/mds.20481. PMID: 15852364.
264. Papapetropoulos S, Farrer MJ, Stone JT, Milkovic NM, Ross OA, Calvo L, McQuorquodale D, Mash DC. Phenotypic associations of tau and ApoE in Parkinson's disease. Neurosci Lett. 2007 Mar 6;414(2):141-4. doi: 10.1016/j.neulet.2006.12.008. Epub 2007 Jan 3. PMID: 17204369.
265. Feldman B, Chapman J, Korczyn AD. Apolipoprotein epsilon4 advances appearance of psychosis in patients with Parkinson's disease. Acta Neurol Scand. 2006 Jan;113(1):14-7. doi: 10.1111/j.1600-0404.2005.00535.x. PMID: 16367893.
266. Monsell SE, Besser LM, Heller KB, Checkoway H, Litvan I, Kukull WA. Clinical and pathologic presentation in Parkinson's disease by apolipoprotein e4 allele status. Parkinsonism Relat Disord. 2014 May;20(5):503-7. doi: 10.1016/j.parkreldis.2014.02.001. Epub 2014 Feb 13. PMID: 24582705; PMCID: PMC4028373.
267. Vaughan RA, Foster JD. Mechanisms of dopamine transporter regulation in normal and disease states. Trends Pharmacol Sci. 2013 Sep;34(9):489-96. doi: 10.1016/j.tips.2013.07.005. Epub 2013 Aug 20. PMID: 23968642; PMCID: PMC3831354.
268. Kim JW, Kim DH, Kim SH, Cha JK. Association of the dopamine transporter gene with Parkinson's disease in Korean patients. J Korean Med Sci. 2000 Aug;15(4):449-51. doi: 10.3346/jkms.2000.15.4.449. PMID: 10983695; PMCID: PMC3054662.
269. Wang J, Liu Z, Chen B. [Association between genetic polymorphism of dopamine transporter gene and susceptibility to Parkinson's disease]. Zhonghua Yi Xue Za Zhi. 2000 May;80(5):346-8. Chinese. PMID: 11798784.
270. Le Couteur DG, Leighton PW, McCann SJ, Pond Sm. Association of a polymorphism in the dopamine-transporter gene with Parkinson's disease. Mov Disord. 1997 Sep;12(5):760-3. doi: 10.1002/mds.870120523. PMID: 9380062.
271. Kaiser R, Hofer A, Grapengiesser A, Gasser T, Kupsch A, Roots I, Brockmöller J. L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Neurology. 2003 Jun 10;60(11):1750-5. doi: 10.1212/01.wnl.0000068009.32067.a1. PMID: 12796525.
272. Radojević B, Dragašević-Mišković NT, Marjanović A, Branković M, Dobričić V, Milovanović A, Tomić A, Svetel M, Petrović I, Jančić I, Stanisavljević D, Savić MM, Kostić VS. Clinical and Genetic Analysis of Psychosis in Parkinson's Disease. J Parkinsons Dis. 2021;11(4):1973-1980. doi: 10.3233/JPD-212716. PMID: 34151861.
273. Schumacher-Schuh AF, Francisconi C, Altmann V, Monte TL, Callegari-Jacques SM, Rieder CR, Hutz MH. Polymorphisms in the dopamine transporter gene are associated with visual hallucinations and levodopa equivalent dose in Brazilians with Parkinson's disease. Int J Neuropsychopharmacol. 2013 Jul;16(6):1251-1258. doi: 10.1017/S1461145712001666. Epub 2013 Jan 30. PMID: 23363854.
274. Wang J, Zhao C, Chen B, Liu ZL. Polymorphisms of dopamine receptor and transporter genes and hallucinations in Parkinson's disease. Neurosci Lett. 2004 Jan 30;355(3):193-6. doi: 10.1016/j.neulet.2003.11.006. Erratum in: Neurosci Lett. 2004 Aug 5;366(1):112. PMID: 14732464.
275. Damasceno Dos Santos EU, Duarte EBC, Miranda LMR, Asano AGC, Asano NMJ, Maia MMD, de Souza PRE. Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease. J Clin Pharmacol. 2019 Jul;59(7):1006-1013. doi: 10.1002/jcph.1394. Epub 2019 Feb 22. PMID: 30794329.
276. Redenšek S, Flisar D, Kojović M, Gregorič Kramberger M, Georgiev D, Pirtošek Z, Trošt M, Dolžan V. Dopaminergic Pathway Genes Influence Adverse Events Related to Dopaminergic Treatment in Parkinson's Disease. Front Pharmacol. 2019 Jan 28;10:8. doi: 10.3389/fphar.2019.00008. PMID: 30745869; PMCID: PMC6360186.
277. Makoff AJ, Graham JM, Arranz MJ, Forsyth J, Li T, Aitchison KJ, Shaikh S, Grünewald RA. Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease. Pharmacogenetics. 2000 Feb;10(1):43-8. doi: 10.1097/00008571-200002000-00006. PMID: 10739171.
278. Fujii C, Harada S, Ohkoshi N, Hayashi A, Yoshizawa K, Ishizuka C, Nakamura T. Association between polymorphism of the cholecystokinin gene and idiopathic Parkinson's disease. Clin Genet. 1999 Nov;56(5):394-9. doi: 10.1034/j.1399-0004.1999.560508.x. PMID: 10668930.
279. Wang J, Si YM, Liu ZL, Yu L. Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease. Pharmacogenetics. 2003 Jun;13(6):365-9. doi: 10.1097/00008571-200306000-00008. PMID: 12777967.
280. Goldman JG, Goetz CG, Berry-Kravis E, Leurgans S, Zhou L. Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system. Arch Neurol. 2004 Aug;61(8):1280-4. doi: 10.1001/archneur.61.8.1280. PMID: 15313848.
281. Goldman JG, Marr D, Zhou L, Ouyang B, Leurgans SE, Berry-Kravis E, Goetz CG. Racial differences may influence the role of cholecystokinin polymorphisms in Parkinson's disease hallucinations. Mov Disord. 2011 Aug 1;26(9):1781-2. doi: 10.1002/mds.23655. Epub 2011 Apr 19. PMID: 21506165; PMCID: PMC3142314.
282. De Luca V, Annesi G, De Marco EV, de Bartolomeis A, Nicoletti G, Pugliese P, Muscettola G, Barone P, Quattrone A. HOMER1 promoter analysis in Parkinson's disease: association study with psychotic symptoms. Neuropsychobiology. 2009;59(4):239-45. doi: 10.1159/000230689. Epub 2009 Jul 31. PMID: 19648775.
283. Schumacher-Schuh AF, Altmann V, Rieck M, Tovo-Rodrigues L, Monte TL, Callegari-Jacques SM, Medeiros MS, Rieder CR, Hutz MH. Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients. Pharmacogenomics J. 2014 Jun;14(3):289-94. doi: 10.1038/tpj.2013.37. Epub 2013 Oct 15. PMID: 24126708.
284. Lin JJ, Yueh KC, Lin SZ, Harn HJ, Liu JT. Genetic polymorphism of the angiotensin converting enzyme and L-dopa-induced adverse effects in Parkinson's disease. J Neurol Sci. 2007 Jan 31;252(2):130-4. doi: 10.1016/j.jns.2006.10.018. Epub 2006 Dec 28. PMID: 17196621.
285. Pascale E, Purcaro C, Passarelli E, Guglielmi R, Vestri AR, Passarelli F, Meco G. Genetic polymorphism of Angiotensin-Converting Enzyme is not associated with the development of Parkinson's disease and of L-dopa-induced adverse effects. J Neurol Sci. 2009 Jan 15;276(1-2):18-21. doi: 10.1016/j.jns.2008.08.017. Epub 2008 Sep 20. PMID: 18805557.
286. Pérez-Santamarina E, García-Ruiz P, Martínez-Rubio D, Ezquerra M, Pla-Navarro I, Puente J, Martí MJ, Palau F, Hoenicka J. Regulatory rare variants of the dopaminergic gene ANKK1 as potential risk factors for Parkinson's disease. Sci Rep. 2021 May 10;11(1):9879. doi: 10.1038/s41598-021-89300-6. Erratum in: Sci Rep. 2022 Jul 26;12(1):12719. PMID: 33972609; PMCID: PMC8110570.
287. Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A. The neuropsychiatry of Parkinson's disease: advances and challenges. Lancet Neurol. 2022 Jan;21(1):89-102. doi: 10.1016/S1474-4422(21)00330-6. PMID: 34942142; PMCID: PMC8800169.
288. Creese B, Ballard C, Aarsland D, Londos E, Sharp S, Jones E. Determining the association of the 5HTTLPR polymorphism with delusions and hallucinations in Lewy body dementias. Am J Geriatr Psychiatry. 2014 Jun;22(6):580-6. doi: 10.1016/j.jagp.2012.11.001. Epub 2013 Apr 9. PMID: 23582751.
289. Sawada H, Oeda T, Umemura A, Tomita S, Hayashi R, Kohsaka M, Yamamoto K, Sudoh S, Sugiyama H. Subclinical elevation of plasma C-reactive protein and illusions/hallucinations in subjects with Parkinson's disease: case-control study. PLoS One. 2014 Jan 31;9(1):e85886. doi: 10.1371/journal.pone.0085886. PMID: 24497930; PMCID: PMC3908859.
290. Redenšek S, Jenko Bizjan B, Trošt M, Dolžan V. Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson's Disease. Int J Neuropsychopharmacol. 2020 Nov 26;23(8):496-504. doi: 10.1093/ijnp/pyaa028. PMID: 32710539; PMCID: PMC7689202.
291. Gao L, Díaz-Corrales FJ, Carrillo F, Díaz-Martín J, Caceres-Redondo MT, Carballo M, Palomino A, López-Barneo J, Mir P. Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson's disease. Acta Neurol Scand. 2010 Jul;122(1):41-5. doi: 10.1111/j.1600-0404.2009.01253.x. Epub 2010 Jan 19. PMID: 20085561.
292. Ramezani M, Ruskey JA, Martens K, Kibreab M, Javer Z, Kathol I, Hammer T, Cheetham J, Leveille E, Martino D, Sarna JR, Gan-Or Z, Pfeffer G, Ismail Z, Monchi O. Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease. Front Neurol. 2021 Jan 14;11:587992. doi: 10.3389/fneur.2020.587992. PMID: 33584494; PMCID: PMC7874164.
293. Gordon PC, Rocha MS, Kauark RG, Costa CD, de Oliveira MO, Godinho F, Borges V. Validation of the National Institute of Neurological Disorders and Stroke Criteria for Psychosis in Parkinson Disease. Am J Geriatr Psychiatry. 2017 Jan;25(1):73-80. doi: 10.1016/j.jagp.2016.08.011. Epub 2016 Aug 26. PMID: 27742525.
294. Sahoo S, Grover S. Psychotic symptoms in patients with Parkinson's disease: A case report and overview of management. J Geriatr Ment Health. 2017; 4:58-63
295. Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y, Hand A, Schapira AH. The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study. Mov Disord. 2007 Oct 15;22(13):1901-11. doi: 10.1002/mds.21596. PMID: 17674410.
296. Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord. 2007 Jan;22(1):41-7. doi: 10.1002/mds.21198. PMID: 17115387.
297. Sawada H, Oeda T. Protocol for a randomised controlled trial: efficacy of donepezil against psychosis in Parkinson's disease (EDAP). BMJ Open. 2013 Sep 25;3(9):e003533. doi: 10.1136/bmjopen-2013-003533. Erratum in: BMJ Open. 2016 Sep 02;6(9):e003533corr1. PMID: 24071461; PMCID: PMC3787472.
298. Voss T, Bahr D, Cummings J, Mills R, Ravina B, Williams H. Performance of a shortened Scale for Assessment of Positive Symptoms for Parkinson's disease psychosis. Parkinsonism Relat Disord. 2013 Mar;19(3):295-9. doi: 10.1016/j.parkreldis.2012.10.022. Epub 2012 Dec 1. PMID: 23211417.
299. Rodríguez-Violante M, Cervantes-Arriaga A, Velázquez-Osuna S, Llorens-Arenas R, Calderón-Fajardo H, Piña-Fuentes D, Martinez-Martin P. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA. Parkinsons Dis. 2014;2014:260485. doi: 10.1155/2014/260485. Epub 2014 Oct 23. PMID: 25400976; PMCID: PMC4226183.
300. Mosley PE, Moodie R, Dissanayaka N. Caregiver Burden in Parkinson Disease: A Critical Review of Recent Literature. J Geriatr Psychiatry Neurol. 2017 Sep;30(5):235-252. doi: 10.1177/0891988717720302. Epub 2017 Jul 26. PMID: 28743212.
301. Adelman RD, Tmanova LL, Delgado D, Dion S, Lachs MS. Caregiver burden: a clinical review. JAMA. 2014 Mar 12;311(10):1052-60. doi: 10.1001/jama.2014.304. PMID: 24618967.
302. Friedman JH. Parkinson disease psychosis: Update. Behav Neurol. 2013 Jan 1;27(4):469-77. doi: 10.3233/BEN-129016. PMID: 23242358; PMCID: PMC5214983.
303. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology. 2001 Jun;56(11 Suppl 5):S1-S88. doi: 10.1212/wnl.56.suppl_5.s1. PMID: 11402154.
304. Thomsen TR, Panisset M, Suchowersky O, Goodridge A, Mendis T, Lang AE. Impact of standard of care for psychosis in Parkinson disease. J Neurol Neurosurg Psychiatry. 2008 Dec;79(12):1413-5. doi: 10.1136/jnnp.2008.153163. PMID: 19010958.
305. Factor SA, Molho ES, Friedman JH. Risperidone and Parkinson's disease. Mov Disord. 2002 Jan;17(1):221-2. doi: 10.1002/mds.1258. PMID: 11835472.
306. Ford B, Lynch T, Greene P. Risperidone in Parkinson's disease. Lancet. 1994 Sep 3;344(8923):681. doi: 10.1016/s0140-6736(94)92114-8. PMID: 7520964.
307. Breier A, Sutton VK, Feldman PD, Kadam DL, Ferchland I, Wright P, Friedman JH. Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson's disease. Biol Psychiatry. 2002 Sep 1;52(5):438-45. doi: 10.1016/s0006-3223(02)01392-6. PMID: 12242060.
308. Ondo WG, Levy JK, Vuong KD, Hunter C, Jankovic J. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord. 2002 Sep;17(5):1031-5. doi: 10.1002/mds.10217. PMID: 12360554.
309. Pintor L, Valldeoriola F, Baillés E, Martí MJ, Muñiz A, Tolosa E. Ziprasidone versus clozapine in the treatment of psychotic symptoms in Parkinson disease: a randomized open clinical trial. Clin Neuropharmacol. 2012 Mar-Apr;35(2):61-6. doi: 10.1097/WNF.0b013e31824d5115. PMID: 22388466.
310. Schindehütte J, Trenkwalder C. Treatment of drug-induced psychosis in Parkinson's disease with ziprasidone can induce severe dose-dependent off-periods and pathological laughing. Clin Neurol Neurosurg. 2007 Feb;109(2):188-91. doi: 10.1016/j.clineuro.2006.07.003. Epub 2006 Sep 1. PMID: 16949733.
311. Fernandez HH, Trieschmann ME, Friedman JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol. 2004 Jan-Feb;27(1):4-5. doi: 10.1097/00002826-200401000-00003. PMID: 15090928.
312. Kwan, C., Frouni, I., Huot, P. (2021). Pharmacotherapy of Psychosis in Parkinson’s Disease. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_439-1
313. FDA Public Health Advisory. Deaths with antipsychotics in elderlypatients with behavioral disturbances. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationfor patients and providers/ucm053171. Accessed 11 April 2005.
314. Trifirò G, Verhamme KM, Ziere G, Caputi AP, Ch Stricker BH, Sturkenboom MC. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf. 2007 May;16(5):538-44. doi: 10.1002/pds.1334. PMID: 17036366.
315. Wu CS, Tsai YT, Tsai HJ. Antipsychotic drugs and the risk of ventricular arrhythmia and/or sudden cardiac death: a nation-wide case-crossover study. J Am Heart Assoc. 2015 Feb 23;4(2):e001568. doi: 10.1161/JAHA.114.001568. PMID: 25713294; PMCID: PMC4345877.
316. McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O'Brien J, Playfer J, Reid W; International Psychogeriatric Association Expert Meeting on DLB. Dementia with Lewy bodies. Lancet Neurol. 2004 Jan;3(1):19-28. doi: 10.1016/s1474-4422(03)00619-7. PMID: 14693108.
317. Forsaa EB, Larsen JP, Wentzel-Larsen T, Alves G. What predicts mortality in Parkinson disease?: a prospective population-based long-term study. Neurology. 2010 Oct 5;75(14):1270-6. doi: 10.1212/WNL.0b013e3181f61311. PMID: 20921512.
318. Badcock JC, Larøi F, Kamp K, Kelsall-Foreman I, Bucks RS, Weinborn M, Begemann M, Taylor JP, Collerton D, O'Brien JT, El Haj M, Ffytche D, Sommer IE. Hallucinations in Older Adults: A Practical Review. Schizophr Bull. 2020 Dec 1;46(6):1382-1395. doi: 10.1093/schbul/sbaa073. PMID: 32638012; PMCID: PMC7707075.
319. Sanagawa A, Shiraishi N, Sekiguchi F, Akechi T, Kimura K. Successful Use of Brexpiprazole for Parkinson's Disease Psychosis Without Adverse Effects: A Case Report. J Clin Psychopharmacol. 2019 Nov/Dec;39(6):685-687. doi: 10.1097/JCP.0000000000001127. PMID: 31688389.
320. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-41. doi: 10.1016/S0140-6736(08)61764-X. Epub 2008 Dec 6. PMID: 19058842.
321. Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease. N Engl J Med. 1999 Mar 11;340(10):757-63. doi: 10.1056/NEJM199903113401003. PMID: 10072410.
322. Clozapine in drug-induced psychosis in Parkinson's disease. The French Clozapine Parkinson Study Group. Lancet. 1999 Jun 12;353(9169):2041-2. PMID: 10376627.
323. Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, Shulman LM, Gronseth G, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):996-1002. doi: 10.1212/01.wnl.0000215428.46057.3d. PMID: 16606910.
324. Frieling H, Hillemacher T, Ziegenbein M, Neundörfer B, Bleich S. Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007 Feb;17(3):165-71. doi: 10.1016/j.euroneuro.2006.08.007. Epub 2006 Oct 27. PMID: 17070675.
325. Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C. The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease. Mov Disord. 2011 Oct;26 Suppl 3(0 3):S42-80. doi: 10.1002/mds.23884. PMID: 22021174; PMCID: PMC4020145.
326. Kapur S, Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci. 2000 Mar;25(2):161-6. PMID: 10740989; PMCID: PMC1408069.
327. Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY. Occupancy of striatal and extrastriatal dopamine D2 receptors by clozapine and quetiapine. Neuropsychopharmacology. 2006 Sep;31(9):1991-2001. doi: 10.1038/sj.npp.1301108. Epub 2006 May 31. PMID: 16738543.
328. Honigfeld G, Arellano F, Sethi J, Bianchini A, Schein J. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry. 1998;59 Suppl 3:3-7. PMID: 9541331.
329. Hack N, Fayad SM, Monari EH, Akbar U, Hardwick A, Rodriguez RL, Malaty IA, Romrell J, Wagle Shukla AA, McFarland N, Ward HE, Okun MS. An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting. PLoS One. 2014 Mar 19;9(3):e91545. doi: 10.1371/journal.pone.0091545. PMID: 24646688; PMCID: PMC3960134.
330. Thomas AA, Friedman JH. Current use of clozapine in Parkinson disease and related disorders. Clin Neuropharmacol. 2010 Jan-Feb;33(1):14-6. doi: 10.1097/WNF.0b013e3181c47168. PMID: 20023573.
331. Haidary HA, Padhy RK. Clozapine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK535399/
332. Yuen JWY, Kim DD, Procyshyn RM, White RF, Honer WG, Barr AM. Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review. Front Neurosci. 2018 Apr 4;12:203. doi: 10.3389/fnins.2018.00203. PMID: 29670504; PMCID: PMC5893810.
333. Richelson E. Preclinical pharmacology of neuroleptics: focus on new generation compounds. J Clin Psychiatry. 1996;57 Suppl 11:4-11. PMID: 8941166.
334. Rabey JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C. Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind labeled study of 3 months' duration. Mov Disord. 2007 Feb 15;22(3):313-8. doi: 10.1002/mds.21116. PMID: 17034006.
335. Shotbolt P, Samuel M, Fox C, David AS. A randomized controlled trial of quetiapine for psychosis in Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:327-32. doi: 10.2147/ndt.s5335. Epub 2009 Jun 10. PMID: 19557142; PMCID: PMC2699657.
336. Ondo WG, Tintner R, Voung KD, Lai D, Ringholz G. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. Mov Disord. 2005 Aug;20(8):958-63. doi: 10.1002/mds.20474. PMID: 15800937.
337. Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, Weintraub D, Sampaio C; the collaborators of the Parkinson's Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee. Update on treatments for nonmotor symptoms of Parkinson's disease-an evidence-based medicine review. Mov Disord. 2019 Feb;34(2):180-198. doi: 10.1002/mds.27602. Epub 2019 Jan 17. Erratum in: Mov Disord. 2019 May;34(5):765. PMID: 30653247; PMCID: PMC6916382.
338. Aarsland D, Emre M, Lees A, Poewe W, Ballard C. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007 Jan 2;68(1):80; author reply 81. doi: 10.1212/01.wnl.0000252956.34585.a6. PMID: 17200503.
339. Morgante L, Epifanio A, Spina E, Zappia M, Di Rosa AE, Marconi R, Basile G, Di Raimondo G, La Spina P, Quattrone A. Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol. 2004 Jul-Aug;27(4):153-6. doi: 10.1097/01.wnf.0000136891.17006.ec. Erratum in: Clin Neuropharmacol. 2004 Sep-Oct;27(5):256. PMID: 15319699.
340. Merims D, Balas M, Peretz C, Shabtai H, Giladi N. Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson's disease psychosis. Clin Neuropharmacol. 2006 Nov-Dec;29(6):331-7. doi: 10.1097/01.WNF.0000236769.31279.19. PMID: 17095896.
341. Marek GJ, Carpenter LL, McDougle CJ, Price LH. Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology. 2003 Feb;28(2):402-12. doi: 10.1038/sj.npp.1300057. Epub 2002 Sep 13. PMID: 12589395.
342. Hamadjida A, Nuara SG, Gourdon JC, Huot P. The effect of mianserin on the severity of psychosis and dyskinesia in the parkinsonian marmoset. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:367-371. doi: 10.1016/j.pnpbp.2017.09.001. Epub 2017 Sep 5. PMID: 28882428.
343. Hamadjida A, Nuara SG, Veyres N, Frouni I, Kwan C, Sid-Otmane L, Harraka MJ, Gourdon JC, Huot P. The effect of mirtazapine on dopaminergic psychosis and dyskinesia in the parkinsonian marmoset. Psychopharmacology (Berl). 2017 Mar;234(6):905-911. doi: 10.1007/s00213-017-4530-z. Epub 2017 Jan 27. PMID: 28130646.
344. Godschalx-Dekker JA, Siegers HP. Reduction of parkinsonism and psychosis with mirtazapine: a case report. Pharmacopsychiatry. 2014 May;47(3):81-3. doi: 10.1055/s-0034-1367014. Epub 2014 Feb 6. PMID: 24504487.
345. Tagai K, Nagata T, Shinagawa S, Tsuno N, Ozone M, Nakayama K. Mirtazapine improves visual hallucinations in Parkinson's disease: a case report. Psychogeriatrics. 2013 Jun;13(2):103-7. doi: 10.1111/j.1479-8301.2012.00432.x. PMID: 23909968.
346. Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR. 5-hydroxytryptamine2A receptor inverse agonists as antipsychotics. J Pharmacol Exp Ther. 2001 Oct;299(1):268-76. PMID: 11561089.
347. Huot P. 5-HT2A receptors and Parkinson's disease psychosis: a pharmacological discussion. Neurodegener Dis Manag. 2018 Dec;8(6):363-365. doi: 10.2217/nmt-2018-0039. Epub 2018 Nov 19. PMID: 30451579.
348. Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, Del Tredici AL, Piu F, Schiffer HH, Ott TR, Burstein ES, Uldam AK, Thygesen MB, Schlienger N, Andersson CM, Son TY, Harvey SC, Powell SB, Geyer MA, Tolf BR, Brann MR, Davis RE. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther. 2006 May;317(2):910-8. doi: 10.1124/jpet.105.097006. Epub 2006 Feb 9. PMID: 16469866.
349. Meltzer HY, Mills R, Revell S, Williams H, Johnson A, Bahr D, Friedman JH. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis. Neuropsychopharmacology. 2010 Mar;35(4):881-92. doi: 10.1038/npp.2009.176. Epub 2009 Nov 11. PMID: 19907417; PMCID: PMC3055369.
350. Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-40. doi: 10.1016/S0140-6736(13)62106-6. Epub 2013 Nov 1. Erratum in: Lancet. 2014 Jul 5;384(9937):28. PMID: 24183563.
351. Yasue I, Matsunaga S, Kishi T, Fujita K, Iwata N. Serotonin 2A Receptor Inverse Agonist as a Treatment for Parkinson's Disease Psychosis: A Systematic Review and Meta-analysis of Serotonin 2A Receptor Negative Modulators. J Alzheimers Dis. 2016;50(3):733-40. doi: 10.3233/JAD-150818. PMID: 26757194.
352. Webster P. Pimavanserin evaluated by the FDA. Lancet. 2018 May 5;391(10132):1762. doi: 10.1016/S0140-6736(18)31002-X. PMID: 29739555.
353. Ballard C, Isaacson S, Mills R, Williams H, Corbett A, Coate B, Pahwa R, Rascol O, Burn DJ. Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis. J Am Med Dir Assoc. 2015 Oct 1;16(10):898.e1-7. doi: 10.1016/j.jamda.2015.06.021. Epub 2015 Aug 1. PMID: 26239690.
354. Rovers JM, Dautzenberg PL, ter Bruggen JP. Rivastigmine als ondersteuning bij het dilemma van de behandeling van hallucinaties optredend bij ziekte van Parkinson [Rivastigmine as adjunctive therapy in the therapeutic dilemma for the treatment of hallucinations due to Parkinson disease]. Tijdschr Gerontol Geriatr. 2006 Jul;37(3):117-20. Dutch. PMID: 16886519.
355. Kurita A, Ochiai Y, Kono Y, Suzuki M, Inoue K. The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson's disease. J Geriatr Psychiatry Neurol. 2003 Sep;16(3):184-8. doi: 10.1177/0891988703256054. PMID: 12967063.
356. Fabbrini G, Barbanti P, Aurilia C, Pauletti C, Lenzi GL, Meco G. Donepezil in the treatment of hallucinations and delusions in Parkinson's disease. Neurol Sci. 2002 Apr;23(1):41-3. doi: 10.1007/s100720200022. PMID: 12111620.
357. Bergman J, Lerner V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Clin Neuropharmacol. 2002 Mar-Apr;25(2):107-10. doi: 10.1097/00002826-200203000-00009. PMID: 11981238.
358. Aarsland D, Hutchinson M, Larsen JP. Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia. Int J Geriatr Psychiatry. 2003 Oct;18(10):937-41. doi: 10.1002/gps.949. PMID: 14533126.
359. Bullock R, Cameron A. Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson's disease: a case series. Curr Med Res Opin. 2002;18(5):258-64. doi: 10.1185/030079902125000813. PMID: 12240787.
360. Ravina B, Putt M, Siderowf A, Farrar JT, Gillespie M, Crawley A, Fernandez HH, Trieschmann MM, Reichwein S, Simuni T. Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005 Jul;76(7):934-9. doi: 10.1136/jnnp.2004.050682. PMID: 15965198; PMCID: PMC1739697.
361. van Mierlo TJM, Foncke EMJ, Post B, Schmand BA, Bloem BR, van Harten B, Tissingh G, Munts AG, de Haan RJ, de Bie RMA; other individuals of the CHEVAL Study Group. Rivastigmine for minor visual hallucinations in Parkinson's disease: A randomized controlled trial with 24 months follow-up. Brain Behav. 2021 Aug;11(8):e2257. doi: 10.1002/brb3.2257. Epub 2021 Jul 21. PMID: 34291590; PMCID: PMC8413762.
362. Dubois B, Tolosa E, Katzenschlager R, Emre M, Lees AJ, Schumann G, Pourcher E, Gray J, Thomas G, Swartz J, Hsu T, Moline ML. Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study. Mov Disord. 2012 Sep 1;27(10):1230-8. doi: 10.1002/mds.25098. Epub 2012 Aug 22. PMID: 22915447.
363. Reading PJ, Luce AK, McKeith IG. Rivastigmine in the treatment of parkinsonian psychosis and cognitive impairment: preliminary findings from an open trial. Mov Disord. 2001 Nov;16(6):1171-4. doi: 10.1002/mds.1204. PMID: 11748755.
364. Voon V, Fox S, Butler TR, Lang AE. Antidepressants and psychosis in Parkinson disease: a case series. Int J Geriatr Psychiatry. 2007 Jun;22(6):601-4. doi: 10.1002/gps.1764. PMID: 17450623.
365. Meco G, Bernardi S. Antidepressant use in treatment of psychosis with comorbid depression in Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30;31(1):311-3. doi: 10.1016/j.pnpbp.2006.06.016. Epub 2006 Aug 17. PMID: 16919377.
366. Lauterbach EC. Dopaminergic hallucinosis with fluoxetine in Parkinson's disease. Am J Psychiatry. 1993 Nov;150(11):1750. doi: 10.1176/ajp.150.11.1750a. PMID: 8214188.
367. Normann C, Hesslinger B, Frauenknecht S, Berger M, Walden J. Psychosis during chronic levodopa therapy triggered by the new antidepressive drug mirtazapine. Pharmacopsychiatry. 1997 Nov;30(6):263-5. doi: 10.1055/s-2007-979504. PMID: 9442549.
368. Matsuda Y, Kishi T, Shibayama H, Iwata N. Yokukansan in the treatment of behavioral and psychological symptoms of dementia: a systematic review and meta-analysis of randomized controlled trials. Hum Psychopharmacol. 2013 Jan;28(1):80-6. doi: 10.1002/hup.2286. PMID: 23359469.
369. Yu CH, Ishii R, Yu SC, Takeda M. Yokukansan and its ingredients as possible treatment options for schizophrenia. Neuropsychiatr Dis Treat. 2014 Sep 1;10:1629-34. doi: 10.2147/NDT.S67607. PMID: 25210456; PMCID: PMC4156002.
370. Hatano T, Hattori N, Kawanabe T, Terayama Y, Suzuki N, Iwasaki Y, Fujioka T; Yokukansan Parkinson’s Disease Study Group. An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson's disease. J Neural Transm (Vienna). 2014;121(3):275-81. doi: 10.1007/s00702-013-1105-y. Epub 2013 Oct 30. PMID: 24169925.
371. Kawanabe T, Yoritaka A, Shimura H, Oizumi H, Tanaka S, Hattori N. Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Mar 17;34(2):284-7. doi: 10.1016/j.pnpbp.2009.11.019. Epub 2009 Dec 3. PMID: 19948198.
372. Abe K, Chiba Y, Katsuse O, Hirayasu Y. A Case of Parkinson Disease With Both Visual Hallucination and Pain Improved by Gabapentin. Clin Neuropharmacol. 2016 Jan-Feb;39(1):55-6. doi: 10.1097/WNF.0000000000000122. PMID: 26757314.
373. Parsons KA, Derkits ME. Visual hallucinations associated with gabapentin use. Am J Health Syst Pharm. 2016 May 15;73(10):631-4. doi: 10.2146/ajhp150136. PMID: 27147215.
374. Nishioka K, Tanaka R, Shimura H, Hirano K, Hatano T, Miyakawa K, Arai H, Hattori N, Urabe T. Quantitative evaluation of electroconvulsive therapy for Parkinson's disease with refractory psychiatric symptoms. J Neural Transm (Vienna). 2014 Nov;121(11):1405-10. doi: 10.1007/s00702-014-1212-4. Epub 2014 Apr 18. PMID: 24744048.
375. Ueda S, Koyama K, Okubo Y. Marked improvement of psychotic symptoms after electroconvulsive therapy in Parkinson disease. J ECT. 2010 Jun;26(2):111-5. doi: 10.1097/YCT.0b013e3181c18a3d. PMID: 20386461.
376. Kennedy R, Mittal D, O'Jile J. Electroconvulsive therapy in movement disorders: an update. J Neuropsychiatry Clin Neurosci. 2003 Fall;15(4):407-21. doi: 10.1176/jnp.15.4.407. PMID: 14627767.
377. Usui C, Hatta K, Doi N, Kubo S, Kamigaichi R, Nakanishi A, Nakamura H, Hattori N, Arai H. Improvements in both psychosis and motor signs in Parkinson's disease, and changes in regional cerebral blood flow after electroconvulsive therapy. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 15;35(7):1704-8. doi: 10.1016/j.pnpbp.2011.05.003. Epub 2011 May 12. PMID: 21605615.
378. Takamiya A, Seki M, Kudo S, Yoshizaki T, Nakahara J, Mimura M, Kishimoto T. Electroconvulsive Therapy for Parkinson's Disease: A Systematic Review and Meta-Analysis. Mov Disord. 2021 Jan;36(1):50-58. doi: 10.1002/mds.28335. Epub 2020 Oct 14. PMID: 33280168.
379. Calderón-Fajardo H, Cervantes-Arriaga A, Llorens-Arenas R, Ramírez-Bermudez J, Ruiz-Chow Á, Rodríguez-Violante M. Electroconvulsive therapy in Parkinson's disease. Arq Neuropsiquiatr. 2015 Oct;73(10):856-60. doi: 10.1590/0004-282X20150131. Epub 2015 Sep 1. PMID: 26331387.
380. KIROV K, RACHEV I. Sluchai na uspeshno izlekuvane na psikhoza pri sledentsefaliten Parkinsonizum s elektroshok [Case of successful electroshock therapy of psychosis in postencephalitis parkinsonism]. Suvr Med (Sofiia). 1956;7(5):89-93. Bulgarian. PMID: 13391605.
381. Hurwitz TA, Calne DB, Waterman K. Treatment of dopaminomimetic psychosis in Parkinson's disease with electroconvulsive therapy. Can J Neurol Sci. 1988 Feb;15(1):32-4. doi: 10.1017/s0317167100027141. PMID: 3345460.
382. Höflich G, Burghof KW, Kasper S, Möller HJ. Elektrokrampftherapie bei Komorbidität einer therapieresistenten paranoid-halluzinatorischen Psychose mit Morbus Parkinson [Electroconvulsive therapy in comorbidity of treatment refractory paranoid hallucinatory psychoses with Parkinson disease]. Nervenarzt. 1994 Mar;65(3):202-5. German. PMID: 7909917.
383. Factor SA, Molho ES, Brown DL. Combined clozapine and electroconvulsive therapy for the treatment of drug-induced psychosis in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1995 Summer;7(3):304-7. doi: 10.1176/jnp.7.3.304. PMID: 7580188.
384. Ozer F, Meral H, Aydin B, Hanoglu L, Aydemir T, Oral T. Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome. J ECT. 2005 Jun;21(2):125-7. doi: 10.1097/01.yct.0000159325.08303.45. PMID: 15905757.
385. Hanin B, Lerner Y, Srour N. An unusual effect of ECT on drug-induced parkinsonism and tardive dystonia. Convuls Ther. 1995 Dec;11(4):271-4. PMID: 8919580.
386. Herzog J, Volkmann J, Krack P, Kopper F, Pötter M, Lorenz D, Steinbach M, Klebe S, Hamel W, Schrader B, Weinert D, Müller D, Mehdorn HM, Deuschl G. Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease. Mov Disord. 2003 Nov;18(11):1332-7. doi: 10.1002/mds.10518. PMID: 14639676.
387. Castelli L, Perozzo P, Zibetti M, Crivelli B, Morabito U, Lanotte M, Cossa F, Bergamasco B, Lopiano L. Chronic deep brain stimulation of the subthalamic nucleus for Parkinson's disease: effects on cognition, mood, anxiety and personality traits. Eur Neurol. 2006;55(3):136-44. doi: 10.1159/000093213. Epub 2006 May 8. PMID: 16682797.
388. Vesper J, Haak S, Ostertag C, Nikkhah G. Subthalamic nucleus deep brain stimulation in elderly patients--analysis of outcome and complications. BMC Neurol. 2007 Mar 16;7:7. doi: 10.1186/1471-2377-7-7. PMID: 17367531; PMCID: PMC1847528.
389. Hanna S, Palmadottir V, Penar PL, Boyd JT. Pallidal stimulation-induced psychosis and suicidality in Parkinson's disease. Clin Park Relat Disord. 2022 Dec 17;8:100175. doi: 10.1016/j.prdoa.2022.100175. PMID: 36594072; PMCID: PMC9803938.
390. Segal GS, Xie SJ, Paracha SU, Grossberg GT. Psychosis in Parkinson's Disease: Current Treatment Options and Impact on Patients and Caregivers. J Geriatr Psychiatry Neurol. 2021 Jul;34(4):274-279. doi: 10.1177/08919887211018280. PMID: 34219522.
391. Diederich NJ, Pieri V, Goetz CG. Coping strategies for visual hallucinations in Parkinson's disease. Mov Disord. 2003 Jul;18(7):831-2. doi: 10.1002/mds.10450. PMID: 12815665.
392. McGorry PD. Psychoeducation in first-episode psychosis: a therapeutic process. Psychiatry. 1995 Nov;58(4):313-28. doi: 10.1080/00332747.1995.11024736. PMID: 8746490.
393. Tarrier N, Wykes T. Is there evidence that cognitive behaviour therapy is an effective treatment for schizophrenia? A cautious or cautionary tale? Behav Res Ther. 2004 Dec;42(12):1377-401. doi: 10.1016/j.brat.2004.06.020. PMID: 15500811.
394. Jenner JA, van de Willige G, Wiersma D. Effectiveness of cognitive therapy with coping training for persistent auditory hallucinations: a retrospective study of attenders of a psychiatric out-patient department. Acta Psychiatr Scand. 1998 Nov;98(5):384-9. doi: 10.1111/j.1600-0447.1998.tb10103.x. PMID: 9845177.
395. Goetz CG, Vogel C, Tanner CM, Stebbins GT. Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology. 1998 Sep;51(3):811-4. doi: 10.1212/wnl.51.3.811. PMID: 9748031.
396. Gordon PC, Kauark RB, Costa CD, de Oliveira MO, Godinho FL, Rocha MS. Clinical Implications of the National Institute of Neurological Disorders and Stroke Criteria for Diagnosing Psychosis in Parkinson's Disease. J Neuropsychiatry Clin Neurosci. 2016 Winter;28(1):26-31. doi: 10.1176/appi.neuropsych.15050119. Epub 2015 Oct 9. PMID: 26449268.