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Published in final edited form as: Drugs Aging. 2016 Dec;33(12):855–863. doi: 10.1007/s40266-016-0416-8

Psychosis in Parkinson Disease: A Review of Etiology, Phenomenology, and Management

Niyatee Samudra 1, Neepa Patel 2, Kyle B Womack 1,3, Pravin Khemani 1, Shilpa Chitnis 1
PMCID: PMC6760850  NIHMSID: NIHMS1051349  PMID: 27830568

Abstract

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT2A receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.

1. Introduction

Parkinson disease (PD) is classically a neurodegenerative disorder characterized by a motor tetrad: (resting) tremor, rigidity, akinesia/bradykinesia, and postural instability [1]. PD pathology is related to the loss of dopaminergic neurons in the pars compacta of the substantia nigra and ventral tegmental (VT) area [2–4]. PD patients may also experience episodes of hallucinations and delusions, which, prior to the widespread use of dopaminergic drugs as therapy (in the 1910s and 1920s), were assumed to be due to a concomitant epidemic of encephalitis lethargica [5]. After the introduction of levodopa and, later, dopamine agonist treatment for PD, hallucinations were reported as medication side effects [6].

Parkinson disease psychosis (PDP), characterized by visual hallucinations and/or other psychotic symptoms, including auditory hallucinations, delusions, or illusions [7], is now considered to be closely associated with PD. In contrast to psychosis due to toxic/metabolic syndromes, PDP presents with a clear (rather than clouded) sensorium [8]. PDP is associated with high mortality, as well as morbidity, for patients, including decreases in health-promoting behaviors and longer nursing home stays [9]. Furthermore, there is a relationship between the development of PDP and other psychiatric diagnoses, including depression and dementia. Finally, PDP is a source of considerable caregiver stress and burnout [10, 11]. Because of its impact on the longevity and quality of life of many PD patients, PDP is a critical treatment target.

Psychosis can be provoked by the drugs used to treat the motor symptoms of PD. Additionally, PDP may be confounded with other conditions associated with psychosis. Therefore, diagnosis and management of psychosis in the setting of PD can be challenging. Treatment may not be indicated for mild hallucinations with retained insight, but becomes necessary in cases impacting quality of life. Atypical antipsychotics, including quetiapine and clozapine, are currently used where therapy for PDP is indicated, although pimavanserin, a novel therapeutic agent targeted to PDP, has been approved in the US. In this article, we review the literature describing PDP phenomenology and risk factors. We also discuss diagnostic and therapeutic approaches to PDP, as well as future directions for research into better treatment options.

2. Clinical Features

2.1. Hallucinations

Visual hallucinations are the most common feature of PDP, in contrast to primary psychotic disorders, where auditory hallucinations are most common. Hallucinations are more frequent in dim lighting or at the end of the day [12]. Patient retention of insight into these hallucinations may fluctuate over time, and may be related to the degree of concomitant cognitive impairment [13]. In a sample of 191 PD patients without dementia to whom the Parkinson Psychosis Rating Scale (PPRS) was administered, 21.5% of participants had psychosis. Visual hallucinations were common in this sample (13.6%). Auditory hallucinations were present in 6.8% of these patients; illusions or misidentification in 7.3%, and paranoid ideation in 4.7% [14].

The characteristics of hallucinations in PD were described in a sample of 216 PD patients [5]. Visual hallucinations were categorized into ‘minor’ and ‘formed’ variants. ‘Formed’ visual hallucinations included various content, such as of persons, familiar or unfamiliar, animals, or objects, while ‘minor’ hallucinations included illusions, such as of presence or of an object’s passage [15]. Minor hallucinations were present in 25.5% of patients; formed or ‘non-minor’ visual hallucinations in 22.2% (isolated in9.3%), and auditory hallucinations in 9.7% (isolated in 2.3%).

Although less common than visual hallucinations, auditory hallucinations have been reported in PDP. In another study, among a sample of 121 clinic patients with PD, 8% were reported to have auditory hallucinations [16]. None had auditory hallucinations unaccompanied by visual hallucinations, and all patients with auditory hallucinations were cognitively impaired. Auditory hallucinations were non-command and non-paranoid in this sample.

2.2. Delusions

Erotomanic, jealous, and persecutory delusions have been reported in PD [17], and there are case reports of Cotard syndrome (‘nihilistic delusion’ or self-negation) and Capgras syndrome (delusion that a friend or family member has been ‘replaced’) in PD patients [18–20]. Delusional jealousy (Othello syndrome) was observed in 20 of 805 patients with PD (approximately 2%), with a significant association with dopamine agonist therapy, and, in a small sample of five patients, was shown to be treatable with dopamine agonist therapy reduction [21, 22].

3. Diagnostic Criteria

A 2007 National Institute of Neurological Disorders and Stroke/National Institute of Mental Health (NINDS/NIMH) work group composed a consensus diagnostic criteria of psychosis in Parkinson disease [23, 24], which included recurrent or continuous symptoms, namely delusions, hallucinations, or other ‘minor hallucinations’ in the setting of a diagnosis of idiopathic PD, without another medical explanation, for at least 1 month. These manifestations may occur with or without insight, dementia, or medication-treated PD [24, 25].

4. Risk Factors

Various factors impact the risk of developing psychosis in a patient with PD. In a study of 775 PD patients taken off dopaminergic therapy, disease duration and severity, as well as therapy with dopamine agonists and catechol-O-methyltransferase (COMT) inhibitors, were predictors of increased psychosis risk [26]. These 775 patients were a subset of 1008 patients who were members of a Brazilian non-profit organization related to Parkinsonism. The patients fulfilled the Queen Square Brain Bank criteria for PD and did not have other limitations to the performance of motor examinations (including prior stroke, stereotactic neurosurgery). Of these, those who provided informed consent for withdrawal of dopaminergic medications were included.

Furthermore, there is an association between impairment in all cognitive domains and the presence of visual hallucinations [27].

Cognitive impairment, depression, and treatment with anticholinergics are associated with increased risk for PDP [28, 29]. Moustafa et al. found that while PD patients with and without psychosis were impaired on a working memory task compared with controls, PD patients with psychosis had a specific cognitive deficit in transitive inference, a hippocampal task [30]. Additionally, they found that Mini-Mental State Examination (MMSE) scores correlated directly with psychosis severity, as measured by the Thought Disorder subscale of the Unified Parkinson Disease Rating Scale (UPDRS); however, psychosis has also been observed in PD patients without dementia. Of a sample of 175 outpatients with early untreated PD without dementia, 2.3% exhibited delusions and hallucinations [31].

The relationship between PD medications and PDP is unclear. Psychosis risk is increased with anticholinergic medications. In contrast, treatment with cholinesterase inhibitors, such as donepezil and rivastigmine, can ameliorate psychosis [28, 32]. Treatment with dopaminergic medications has been implicated as a psychosis risk factor, although the risk is not substantiated. For instance, in a sample of 102 PD outpatients, with more than 80% receiving levodopa therapy, Holroyd et al. found stronger associations between visual hallucinations and patient characteristics, such as disease severity, dementia, depression, and worse visual acuity, than with dopaminergic medication dosage [12]. Even among dopaminergic therapies, it is unclear whether levodopa or dopamine agonists contribute more to psychosis [33, 34]. Psychosis has also been reported in cases of subthalamic deep brain stimulation [35].

In a study of 87 patients with advanced PD, including 50 patients diagnosed with psychosis, carrying the apolipoprotein E (ApoE) epsilon4 allele was a risk factor for earlier appearance of psychosis [36]. Epsilon4 (in contrast to epsilon2) is associated with smaller hippocampal volumes in carriers, which is also associated with earlier onset of Alzheimer’s disease [37]; smaller hippocampal volumes are also associated with primary psychotic disorders [38, 39]. A recent comprehensive review implicates polymorphisms in the cholecystokinin (CCK) gene in PD psychosis [40].

5. Pathophysiology

Extrinsic (drug-related) and intrinsic (neurotransmitter dysfunction-related) causes of PDP have been suggested. One hypothesis is that degeneration and overstimulation of mesolimbic dopaminergic neurons (specifically in the substantia nigra and VT area) contribute to degeneration in linked areas associated with different neurotransmitters, including locus coeruleus (norepinephrine), nucleus basalis (acetylcholine), and dorsal raphe nuclei (5-hydroxytryptamine [5-HT]) [41]. The functions of dopamine and acetylcholine may be linked because of the role of limbic nicotinic cholinergic receptors in dopamine release [42].

5.1. Neurotransmitter Hypotheses

Although the precise pathophysiology of PDP has not been elucidated, various neurotransmitter systems are being studied.

5.1.1. Dopamine

Degeneration of dopaminergic neurons in the ventral dopaminergic pathway is implicated in PDP because of disruption in limbic and cortical projections from the VT area. Dirnberger et al. found altered pallidal-frontal dopamine processing in six non-depressed, non-demented PD patients, compared with healthy controls, on an executive function task [43]. Overstimulation of striatal/mesolimbic dopamine receptors may be associated with the generation of visual hallucinations [42]. These studies suggest the possibility of striatal dopaminergic impairment influencing frontal regions, providing a pathway for psychosis induction in PD. Therefore, withdrawing or decreasing levels of dopaminergic medications may alleviate psychotic symptoms in PDP.

5.1.2. Acetylcholine

Loss of cholinergic neurons in the nucleus basalis of Meynert is associated with PD progression [44], while cholinergic deficits may be associated with visual hallucinations in PDP [45]. The pedunculopontine nucleus pars compacta (PPNc) is a cholinergic nucleus whose degeneration is associated with PD pathology. Some investigators have found increased volume loss in PPNc in PD patients compared with both normal controls and dementia with Lewy bodies (DLB) patients with visual hallucinations [46, 47].

5.1.3. Serotonin

Serotonin has been implicated in psychosis generation because of the action of 5-HT1A receptor agonists, including lysergic acid diethylamide (LSD), in producing visual hallucinations. The history of serotonergic drug use in PD dates to initial studies using methysergide (a serotonin antagonist with concerning side effects, including retroperitoneal fibrosis) ineffectively for the treatment of PD [48]. More recently, atypical antipsychotics, which block 5-HT as well as dopamine receptors, have been considered for reducing PDP symptoms. Pimavanserin, a new 5-HT2A receptor inverse agonist, has been approved for the treatment of PDP [24, 49]. Part of the antipsychotic action of pimavanserin may be attributable to the role of 5-HT2A receptor inverse agonists in preferentially releasing dopamine in the cortex, rather than the limbic system [49]. It is promising, in conjunction with risperidone, for the treatment of schizophrenia, allowing for decreased use of risperidone for this indication and reducing the risk of extrapyramidal symptoms [50].

5.2. Functional and Structural Imaging Studies

Visual hallucinations may be related to visual pathway disruption. This includes ocular dysfunction, including color discrimination, alterations in visual acuity, retinal dysfunction, diplopia, and blindness (monocular or binocular) [8, 51–53].

Patients with visual hallucinations may also have structural anomalies of the cortical visual processing system, such as gray matter atrophy in several cerebral and cerebellar areas [54–57]. Another notable pathologic marker of visual hallucinations in PDP is the presence of Lewy bodies in the temporal lobe. Well-formed visual hallucinations are associated with the presence of brainstem Lewy bodies, especially in the amygdala and the parahippocampal region [58]. PD patients with visual hallucinations have demonstrated functional imaging differences compared with controls. In a visual processing task, Stebbins et al. found a shift in the processing of strobe stimuli from posterior (visual cortical, including occipital, temporal, parietal posterior cortex) to anterior (attention-related, superior frontal) brain areas in 12 PD patients with visual hallucinations compared with matched PD non-hallucinators, suggesting altered functional visual pathways [59]. Ramirez-Ruiz et al. demonstrated hyperactivation of the inferior frontal gyrus in PD patients with visual hallucinations during a one-back task [60], while Kiferle et al. showed increased caudate uptake in 18 patients with visual hallucinations in a single-photon emission computed tomography (SPECT) study [61]. The results of these and similar studies suggest a derangement in attention and vision networks. Deficits in bottom-up processing and abnormalities in fronto-striatal networks in PD patients may be the basis for hallucinations.

6. Management Approaches

6.1. Assessment

No rating scales have yet been validated for the measurement of PDP, although the Brief Psychiatric Rating Scale (BPRS) for PD, the PPRS, the Neuropsychiatric Inventory (NPI), the UPDRS Thought Disorder subscale, and the Scale for Assessment of Positive Symptoms (SAPS) for PD have been used clinically as well as in research contexts [62]. The pareidolia test assesses for a subject’s propensity for, and ability to perceive, complex visual illusions. Patients with DLB tend to experience pareidolias more often and this test may also help differentiate PD patients with psychosis from healthy controls [63, 64]. Currently, the diagnosis of PDP is made on the basis of clinical presentation of recurrent delusions and hallucinations for at least 1 month.

6.2. Diagnostic Work-Up

Diagnosing PDP entails ruling out other causes of the presenting symptoms. Laboratory tests, including clinically appropriate workup for causes of possible delirium or exclusion of occult infection (which might include a complete metabolic panel, complete blood count [CBC], thyroid-stimulating hormone level, liver function tests, ammonia, vitamin B12 and folate levels, as well as rapid plasma reagin and urinalysis) may be considered. Brain magnetic resonance imaging (MRI) should be considered for investigating other intracranial processes when psychosis is acute, persistent, and accompanied by other neurological deficits. Patient medications should be reviewed, with special attention given to recent medication changes. Any Beer’s list medication (medications to avoid in the geriatric population, corresponding to the screening tool of older people’s prescriptions/screening tool to alert to right treatment [STOPP/START] tool kit in the UK) should be assessed for necessity [65–67]. Concomitantly, a good caregiver history should be obtained. Clinicians should be alert for the possibility of depression or a primary psychotic disorder as a cause of the presenting hallucinations, and clinically assess for these. Chronology and careful history taking are essential; the onset of psychotic symptoms early in life and/or prior to Parkinsonism point to a primary psychiatric disorder. Acute onset of psychotic symptoms early in the course of Parkinsonism suggests DLB, while psychosis in the context of well-established PD suggests PDP. The Lewy Body Composite Risk Score is a new, rapid scoring method that may improve sensitivity of DLB detection [68].

In addition, the impact of psychotic symptoms on the patient’s life should be determined; very mild symptoms with preserved insight may not require pharmacologic treatment [69]. Subsequently, medications for PD should be adjusted because of their potential to worsen psychosis. A suggested order in the literature for discontinuation of medications is to, first, stop adjuvant medications for PD, including anticholinergics, selegiline, and amantadine; second, stop dopamine agonists and COMT inhibitors; and, lastly, reduce levodopa only if these measures fail [70]. Complete removal of all dopaminergic medications should be avoided to prevent significant worsening of parkinsonian symptoms and, in rare instances, development of neuroleptic malignant syndrome [71, 72].

6.3. Drugs with Promise in the Treatment of Parkinson Disease Psychosis

6.3.1. Quetiapine and Clozapine

Atypical antipsychotics can be used if, after other steps are taken, psychosis symptoms are still troubling and persistent. Clozapine is recommended and is the only antipsychotic with proven efficacy in PDP [73]. Although in a randomized open-label trial of 45 patients with PDP, clozapine and quetiapine were shown to be equally effective in reducing psychotic symptoms, as measured by the BPRS, several subsequent randomized clinical trials (RCTs) demonstrated no change in psychotic outcomes with quetiapine [74–77]. Neither worsened motor symptoms on the UPDRS.

Although there is insufficient evidence for the efficacy of quetiapine, clinicians tend to prefer low-dose quetiapine over clozapine because of the extensive need for monitoring for clozapine-induced agranulocytosis, including weekly CBCs for 6 months, followed by biweekly CBCs, which are then administered monthly after 1 year [70]. Additionally, patients and providers must both be registered with the FDA for clozapine to be prescribed. A recent retrospective chart review of clozapine use in PDP patients at a single center over the course of 8 years demonstrated a low overall retention rate on clozapine, in large part due to the inconvenience of frequent blood testing [78]. However, a danger of using quetiapine is the possibility of sedation and subsequent falls in geriatric patients [79]. Both are atypical antipsychotics and carry the risk of weight gain and the metabolic syndrome. The FDA has also determined that available data show increased mortality with the use of atypical antipsychotics in elderly patients with dementia, and this risk appears to carry into the PD population [80]. However, it is of note that low-dose clozapine can be used to good effect in PDP, and this may allay concerns about the metabolic syndrome in association with clozapine [81]. While maintenance doses of 50–200 mg/day may be typically required for the treatment of psychosis associated with schizophrenia, doses<50 mg/day can be used to good effect in PDP [82, 83]. Generally, clozapine may have a fast onset of action, over a few days to 1 week [84]. In a study of 32 patients with PD and psychosis, over 5 years, the major side effect of clozapine that limited dose uptitration was somnolence [85].

In 2006, the American Academy of Neurology (AAN) released guidelines for the treatment of PDP with atypical antipsychotics. These guidelines recommended the use of clozapine over quetiapine (level C evidence) on the basis of a double-blind prospective cohort study (level B evidence) because clozapine may improve both psychosis and motor function [82, 86, 87]. Clozapine is considered the gold standard in the treatment of PDP. The National Institute for Health and Care Excellence (NICE, UK) 2006 guidelines agree with the use of clozapine and quetiapine, and new guidelines are currently in draft form and are expected in 2017 [88].

6.3.2. Other Antipsychotics

Other antipsychotics have been examined in the treatment of PDP, notably olanzapine, risperidone, ziprasidone (all atypical antipsychotics), and melperone (typical antipsychotic). In double-blind studies, olanzapine has not been shown to be effective in treating psychosis but has resulted in significant motor worsening when compared with placebo or clozapine [89, 90]. Consequently, the AAN does not recommend olanzapine for the treatment of PDP (level B evidence). Risperidone is effective in treating psychosis but has variably resulted in worsening motor symptoms [91]. There is no AAN guideline on the use of risperidone in PDP, while NICE guidelines also recommend against the use of olanzapine [88].

In a very small, open-label, prospective trial, ziprasidone has been shown to ameliorate psychosis symptoms, as assessed by SAPS and BPRS, in 14 patients over 4 weeks [92]; however, it carries a possibility of QT prolongation and an unfavorable extrapyramidal symptom side-effect profile. Melperone may not have the side effect of metabolic syndrome. However, results of an unpublished double-blind, placebo-controlled trial in 2011 suggest that it is ineffective in the treatment of PDP, as assessed by the SAPS, although it did not worsen motor function [93].

6.3.3. Cholinesterase Inhibitors

Because of the close association between severe hallucinations in PD and dementia, cholinesterase inhibitors have been investigated as a therapeutic for PDP. These may be effective in the context of pre-existing visual hallucinations or PD with dementia. In several randomized, placebo-controlled, double-blind trials of donepezil to evaluate cognitive outcomes, psychiatric symptoms as assessed by the NPI were a secondary outcome that did not change between treatment and control groups [94]. However, a 24-week study of rivastigmine for PD dementia among outpatients found improvement in visual hallucination incidence [95]. Of note, hallucinations may be treated with cholinesterase inhibitors in DLB, with a current ongoing clinical trial in PDP [96–98]. Studies with cholinesterase inhibitors are needed, with psychotic symptom reduction in PDP as a primary outcome measure.

6.3.4. Serotonin Agonists/Antagonists

Because of the need for dopaminergic therapy for motor symptoms of PD, there has been strong interest in serotonergic agents for PDP [99]. Both clozapine and quetiapine, which are currently used to treat PDP, are 5-HT2A receptor antagonists. Ondansetron, a 5-HT3 receptor antagonist, has shown some efficacy in the treatment of PDP [100], while pimavanserin, a 5-HT2A receptor inverse agonist, has been approved for PDP in the US. Two double-blinded RCTs have compared pimavanserin with placebo in reducing psychotic symptoms. The first, over the course of 28 days, showed patient improvement on SAPS-based measures, and no decline in motor or cognitive function was seen [101]. In addition, a 6-week-long trial of nearly 200 outpatients showed patient improvement on psychotic symptoms versus placebo on a modified version of the SAPS—the SAPS-PD—without significant adverse effects [102]. Pimavanserin and atypical antipsychotics have not been directly compared.

6.3.5. Other Treatments

Case reports for various antidepressants, including clomipramine, citalopram, and mirtazapine have demonstrated potential efficacy in PDP with comorbid depression or insomnia [103–105]. Electroconvulsive therapy has been shown in a few case reports to benefit PDP patients [106].

Non-interventional treatments for psychosis, including psychoeducation and cognitive behavioral therapy, have shown some benefit in schizophrenia and could also be explored in the setting of PDP [107]. Music therapy has been used with benefit for the affective and behavioral symptoms of PD [108]; however, these therapies would pose challenges in patients with cognitive impairment as some degree of insight would be required.

7. Conclusions

PDP, often manifesting with visual hallucinations, is a common complication of PD. Generally, it is comorbid with significant cognitive impairment, with severe social and occupational consequences for the patient. The pathophysiology of PDP is only partly understood. Therefore, available treatments for PDP are suboptimal. There is a conflict between the need for dopaminergic treatment in PD and the anti-dopaminergic mechanism of most antipsychotics. Of the atypical antipsychotics, clozapine has shown effectiveness in an RCT but its side effects and the need for monitoring are undesirable. Pimavanserin, a 5-HT2A receptor inverse agonist, has recently been approved by the FDA for use in the US [109].

Next steps will likely include investigating similar serotonergic drugs in comparison studies with atypical antipsychotics, as well as further elucidating the role of cholinesterase inhibitors in treatment. Ongoing studies include [A Study of the Safety and Tolerability of Pimavanserin (ACP-103) in Patients With Parkinson’s Disease Psychosis] and [Cholinesterase Inhibitors to Slow Progression of Visual Hallucinations in Parkinson’s Disease], as well as an observational study, [Understanding Hallucinations (Part I)], among others. Further research is needed to identify imaging, genetic, and other clinical biomarkers for PDP, which, in turn, could lead to more targeted therapies.

Key Points.

Parkinson disease psychosis (PDP) is associated with increased morbidity and mortality in Parkinson disease patients.

Decreasing the number and dosage of anti-Parkinson disease drugs, which could alleviate PDP symptoms, might also worsen motor function.

Atypical antipsychotics, including clozapine and quetiapine, have problematic side effects. Clozapine is proven to be effective in PDP, with fewer side effects than quetiapine.

Pimavanserin, a serotonin receptor inverse agonist, has been newly approved in the US to treat PDP.

Acknowledgements

The authors would like to acknowledge Dr. Samarpita Sengupta for providing critical feedback and editorial assistance. In addition, we would like to acknowledge our patients with PD and psychosis, as we hope to continue to improve in our abilities to help them.

Funding During the completion of this manuscript, Drs. Khemani and Chitnis were co-investigators on a project funded by a National Institute of Neurological Diseases and Stroke grant (1U01NS082148). In addition, Dr. Womack was supported by a grant from the National Institute of Aging (P30AG012300).

Footnotes

Conflict of interest Niyatee Samudra, Neepa Patel, Kyle B. Womack, Pravin Khemani, and Shilpa Chitnis report no conflicts of interest.

References

  • 1.Hughes AJ, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Braak H, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211. [DOI] [PubMed] [Google Scholar]
  • 3.Jankovic J Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–76. [DOI] [PubMed] [Google Scholar]
  • 4.Damier P, et al. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain. 1999;122(Pt 8):1437–48. [DOI] [PubMed] [Google Scholar]
  • 5.Fenelon G, et al. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain. 2000;123(Pt 4):733–45. [DOI] [PubMed] [Google Scholar]
  • 6.Factor SA, et al. Parkinson’s disease: drug-induced psychiatric states. Adv Neurol. 1995;65:115–38. [PubMed] [Google Scholar]
  • 7.Aarsland D, et al. Range of neuropsychiatric disturbances in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999;67(4):492–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Diederich NJ, et al. Hallucinations in Parkinson disease. Nat Rev Neurol. 2009;5(6):331–42. [DOI] [PubMed] [Google Scholar]
  • 9.Fenelon G, Alves G. Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci. 2010;289(1–2):12–7. [DOI] [PubMed] [Google Scholar]
  • 10.Thanvi BR, Lo TC, Harsh DP. Psychosis in Parkinson’s disease. Postgrad Med J. 2005;81(960):644–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Aarsland D, et al. Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry. 2007;78(1):36–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Holroyd S, Currie L, Wooten GF. Prospective study of hallucinations and delusions in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2001;70(6):734–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Williams-Gray CH, et al. Cognitive deficits and psychosis in Parkinson’s disease: a review of pathophysiology and therapeutic options. CNS Drugs. 2006;20(6):477–505. [DOI] [PubMed] [Google Scholar]
  • 14.Lee AH, Weintraub D. Psychosis in Parkinson’s disease without dementia: common and comorbid with other non-motor symptoms. Mov Disord. 2012;27(7):858–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Fenelon G, et al. Feeling of presence in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2011;82(11):1219–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Inzelberg R, Kipervasser S, Korczyn AD. Auditory hallucinations in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1998;64(4):533–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Pacchetti C, et al. Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson’s disease. Mov Disord. 2005;20(11):1439–48. [DOI] [PubMed] [Google Scholar]
  • 18.Josephs KA. Capgras syndrome and its relationship to neurodegenerative disease. Arch Neurol. 2007;64(12):1762–6. [DOI] [PubMed] [Google Scholar]
  • 19.Ramirez-Bermudez J, et al. Cotard syndrome in neurological and psychiatric patients. J Neuropsychiatry Clin Neurosci. 2010;22(4):409–16. [DOI] [PubMed] [Google Scholar]
  • 20.Factor SA, Molho ES. Threatening auditory hallucinations and Cotard syndrome in Parkinson disease. Clin Neuropharmacol. 2004;27(5):205–7. [DOI] [PubMed] [Google Scholar]
  • 21.Poletti M, et al. Dopamine agonists and delusional jealousy in Parkinson’s disease: a cross-sectional prevalence study. Mov Disord. 2012;27(13):1679–82. [DOI] [PubMed] [Google Scholar]
  • 22.Georgiev D, et al. Othello syndrome in patients with Parkinson’s disease. Psychiatr Danub. 2010;22(1):94–8. [PubMed] [Google Scholar]
  • 23.Ravina B, et al. Diagnostic criteria for psychosis in Parkinson’s disease: report of an NINDS. NIMH work group. Mov Disord. 2007;22(8):1061–8. [DOI] [PubMed] [Google Scholar]
  • 24.Friedman JH. Parkinson disease psychosis: update. Behav Neurol. 2013;27(4):469–77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Rabey JM. Hallucinations and psychosis in Parkinson’s disease. Parkinsonism Relat Disord. 2009;15(Suppl 4):S105–10. [DOI] [PubMed] [Google Scholar]
  • 26.Munhoz R, et al. Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2013;84(8):883–7. [DOI] [PubMed] [Google Scholar]
  • 27.Factor SA, et al. Cognitive correlates of hallucinations and delusions in Parkinson’s disease. J Neurol Sci. 2014;347(1–2):316–21. [DOI] [PubMed] [Google Scholar]
  • 28.Sawada H, et al. Trigger medications and patient-related risk factors for Parkinson disease psychosis requiring anti-psychotic drugs: a retrospective cohort study. BMC Neurol. 2013;13:145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Giladi N, et al. Risk factors for dementia, depression and psychosis in long-standing Parkinson’s disease. J Neural Transm (Vienna). 2000;107(1):59–71. [DOI] [PubMed] [Google Scholar]
  • 30.Moustafa AA, et al. Cognitive correlates of psychosis in patients with Parkinson’s disease. Cogn Neuropsychiatry. 2014;19(5): 381–98. [DOI] [PubMed] [Google Scholar]
  • 31.Aarsland D, et al. The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2009;80(8):928–30. [DOI] [PubMed] [Google Scholar]
  • 32.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;16(6):1171–4. [DOI] [PubMed] [Google Scholar]
  • 33.Ecker D, et al. Dopamine agonists and their risk to induce psychotic episodes in Parkinson’s disease: a case-control study. BMC Neurol. 2009;9:23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Aarsland D, et al. Prevalence and clinical correlates of psychotic symptoms in Parkinson disease: a community-based study. Arch Neurol. 1999;56(5):595–601. [DOI] [PubMed] [Google Scholar]
  • 35.Widge AS, et al. Psychosis from subthalamic nucleus deep brain stimulator lesion effect. Surg Neurol Int. 2013;4:7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Feldman B, Chapman J, Korczyn AD. Apolipoprotein epsilon4 advances appearance of psychosis in patients with Parkinson’s disease. Acta Neurol Scand. 2006;113(1):14–7. [DOI] [PubMed] [Google Scholar]
  • 37.Alexopoulos P, et al. Hippocampal volume differences between healthy young apolipoprotein E e2 and e4 carriers. J Alzheimers Dis. 2011;26(2):207–10. [DOI] [PubMed] [Google Scholar]
  • 38.Velakoulis D, et al. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Arch Gen Psychiatry. 2006;63(2):139–49. [DOI] [PubMed] [Google Scholar]
  • 39.Arnold SJ, et al. Hippocampal volume is reduced in schizophrenia and schizoaffective disorder but not in psychotic bipolar I disorder demonstrated by both manual tracing and automated parcellation (FreeSurfer). Schizophr Bull. 2015;41(1):233–49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Lenka A, et al. Genetic substrates of psychosis in patients with Parkinson’s disease: a critical review. J Neurol Sci. 2016;364: 33–41. [DOI] [PubMed] [Google Scholar]
  • 41.Wolters EC. Intrinsic and extrinsic psychosis in Parkinson’s disease. J Neurol. 2001;248 Suppl 3:III22–7. [DOI] [PubMed] [Google Scholar]
  • 42.Goetz CG, Tanner CM, Klawans HL. Pharmacology of hallucinations induced by long-term drug therapy. Am J Psychiatry. 1982;139(4):494–7. [DOI] [PubMed] [Google Scholar]
  • 43.Dirnberger G, Frith CD, Jahanshahi M. Executive dysfunction in Parkinson’s disease is associated with altered pallidal-frontal processing. Neuroimage. 2005;25(2):588–99. [DOI] [PubMed] [Google Scholar]
  • 44.Bosboom JL, Stoffers D, Wolters E. Cognitive dysfunction and dementia in Parkinson’s disease. J Neural Transm (Vienna). 2004;111(10–11):1303–15. [DOI] [PubMed] [Google Scholar]
  • 45.Papapetropoulos S, Mash DC. Psychotic symptoms in Parkinson’s disease. From description to etiology. J Neurol. 2005;252(7):753–64. [DOI] [PubMed] [Google Scholar]
  • 46.Janzen J, et al. The pedunculopontine nucleus is related to visual hallucinations in Parkinson’s disease: preliminary results of a voxel-based morphometry study. J Neurol. 2012;259(1):147–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Hepp DH, et al. Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients. J Neuropathol Exp Neurol. 2013;72(12): 1162–70. [DOI] [PubMed] [Google Scholar]
  • 48.Klawans HL, Ringel SP. A clinical study of methysergide in Parkinsonism: evidence against a serotonergic mechanism. J Neurol Sci. 1973;19(4):399–405. [DOI] [PubMed] [Google Scholar]
  • 49.Li Z, et al. ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Psychopharmacology. 2005; 183(2):144–53. [DOI] [PubMed] [Google Scholar]
  • 50.Meltzer HY, et al. Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: comparison with reference dose risperi-done, 6 mg/day. Schizophr Res. 2012;141(2–3):144–52. [DOI] [PubMed] [Google Scholar]
  • 51.Nebe A, Ebersbach G. Selective diplopia in Parkinson’s disease: a special subtype of visual hallucination? Mov Disord. 2007;22(8):1175–8. [DOI] [PubMed] [Google Scholar]
  • 52.Matsui H, et al. Impaired visual acuity as a risk factor for visual hallucinations in Parkinson’s disease. J Geriatr Psychiatry Neurol. 2006;19(1):36–40. [DOI] [PubMed] [Google Scholar]
  • 53.Silva MF, et al. Independent patterns of damage within magno-, parvo- and koniocellular pathways in Parkinson’s disease. Brain. 2005;128(Pt 10):2260–71. [DOI] [PubMed] [Google Scholar]
  • 54.Pagonabarraga J, et al. Neural correlates of minor hallucinations in non-demented patients with Parkinson’s disease. Parkinsonism Relat Disord. 2014;20(3):290–6. [DOI] [PubMed] [Google Scholar]
  • 55.Meppelink AM, et al. Regional cortical grey matter loss in Parkinson’s disease without dementia is independent from visual hallucinations. Mov Disord. 2011;26(1):142–7. [DOI] [PubMed] [Google Scholar]
  • 56.Ramirez-Ruiz B, et al. Cerebral atrophy in Parkinson’s disease patients with visual hallucinations. Eur J Neurol. 2007;14(7): 750–6. [DOI] [PubMed] [Google Scholar]
  • 57.Goldman JG, et al. Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson’s disease with hallucinations. Brain. 2014;137(Pt 3):849–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain. 2002;125(Pt 2):391–403. [DOI] [PubMed] [Google Scholar]
  • 59.Stebbins GT, et al. Altered cortical visual processing in PD with hallucinations: an fMRI study. Neurology. 2004;63(8):1409–16. [DOI] [PubMed] [Google Scholar]
  • 60.Ramirez-Ruiz B, et al. Brain response to complex visual stimuli in Parkinson’s patients with hallucinations: a functional magnetic resonance imaging study. Mov Disord. 2008;23(16):2335–43. [DOI] [PubMed] [Google Scholar]
  • 61.Kiferle L, et al. Caudate dopaminergic denervation and visual hallucinations: evidence from a (1)(2)(3)I-FP-CIT SPECT study. Parkinsonism Relat Disord. 2014;20(7):761–5. [DOI] [PubMed] [Google Scholar]
  • 62.Fernandez HH, et al. Scales to assess psychosis in Parkinson’s disease: critique and recommendations. Mov Disord. 2008;23(4):484–500. [DOI] [PubMed] [Google Scholar]
  • 63.Uchiyama M, et al. Pareidolias: complex visual illusions in dementia with Lewy bodies. Brain. 2012;135(Pt 8):2458–69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Uchiyama M, et al. Pareidolia in Parkinson’s disease without dementia: a positron emission tomography study. Parkinsonism Relat Disord. 2015;21(6):603–9. [DOI] [PubMed] [Google Scholar]
  • 65.Hindle JV. The practical management of cognitive impairment and psychosis in the older Parkinson’s disease patient. J Neural Transm (Vienna). 2013;120(4):649–53. [DOI] [PubMed] [Google Scholar]
  • 66.Campanelli CM. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60(4):616–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.O’Mahony D, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Galvin JE. Improving the clinical detection of lewy body dementia with the lewy body composite risk score. Alzheimers Dement (Amst). 2015;1(3):316–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Zahodne LB, Fernandez HH. Pathophysiology and treatment of psychosis in Parkinson’s disease: a review. Drugs Aging. 2008;25(8):665–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Friedman JH, Factor SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord. 2000;15(2):201–11. [DOI] [PubMed] [Google Scholar]
  • 71.Adnet P, Lestavel P, Krivosic-Horber R. Neuroleptic malignant syndrome. Br J Anaesth. 2000;85(1):129–35. [DOI] [PubMed] [Google Scholar]
  • 72.Toru M, et al. Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. J Nerv Ment Dis. 1981;169(5):324–7. [DOI] [PubMed] [Google Scholar]
  • 73.Eng ML, Welty TE. Management of hallucinations and psychosis in Parkinson’s disease. Am J Geriatr Pharmacother. 2010;8(4):316–30. [DOI] [PubMed] [Google Scholar]
  • 74.Ondo WG, et al. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease. Mov Disord. 2005;20(8):958–63. [DOI] [PubMed] [Google Scholar]
  • 75.Rabey JM, et al. Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months’ duration. Mov Disord. 2007;22(3):313–8. [DOI] [PubMed] [Google Scholar]
  • 76.Prohorov T, et al. The effect of quetiapine in psychotic Parkinsonian patients with and without dementia. An open-labeled study utilizing a structured interview. J Neurol. 200;253(2):171–5. [DOI] [PubMed] [Google Scholar]
  • 77.Morgante L, et al. Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol. 2004;27(4):153–6. [DOI] [PubMed] [Google Scholar]
  • 78.Hack N, et al. An eight-year clinic experience with clozapine use in a Parkinson’s disease clinic setting. PLoS One. 2014;9(3):e91545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Alexopoulos GS, et al. Using antipsychotic agents in older patients. J Clin Psychiatry. 2004;65 Suppl 2:5–99 (discussion 100–102; quiz 103–4). [PubMed] [Google Scholar]
  • 80.Weintraub D, et al. Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurol. 2016;73(5):535–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Ruggieri S, et al. Low dose of clozapine in the treatment of dopaminergic psychosis in Parkinson’s disease. Clin Neuropharmacol. 1997;20(3):204–9. [DOI] [PubMed] [Google Scholar]
  • 82.The Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med. 1999;340(10):757–63. [DOI] [PubMed] [Google Scholar]
  • 83.Gaszner P, Makkos Z. Clozapine maintenance therapy in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(3):465–9. [DOI] [PubMed] [Google Scholar]
  • 84.Zedkova I, et al. Onset of action of atypical and typical antipsychotics in the treatment of adolescent schizophrenic psychoses. Neuro Endocrinol Lett. 2011;32(5):667–70. [PubMed] [Google Scholar]
  • 85.Klein C, et al. Clozapine in Parkinson’s disease psychosis: 5-year follow-up review. Clin Neuropharmacol. 2003;26(1):8–11. [DOI] [PubMed] [Google Scholar]
  • 86.Pollak P, et al. Clozapine in drug induced psychosis in Parkinson’s disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry. 2004;75(5):689–95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Miyasaki JM, et al. 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;66(7):996–1002. [DOI] [PubMed] [Google Scholar]
  • 88.National Collaborating Centre for Chronic Conditions (UK). Parkinson’s disease: national clinical guideline for diagnosis and management in primary and secondary care NICE clinical guidelines, no. 35 London: Royal College of Physicians (UK); 2006. [PubMed] [Google Scholar]
  • 89.Ondo WG, et al. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord. 2002;17(5):1031–5. [DOI] [PubMed] [Google Scholar]
  • 90.Marsh L, Lyketsos C, Reich SG. Olanzapine for the treatment of psychosis in patients with Parkinson’s disease and dementia. Psychosomatics. 2001;42(6):477–81. [DOI] [PubMed] [Google Scholar]
  • 91.Meco G, et al. Risperidone in levodopa-induced psychosis in advanced Parkinson’s disease: an open-label, long-term study. Mov Disord. 1997;12(4):610–2. [DOI] [PubMed] [Google Scholar]
  • 92.Pintor L, et al. Ziprasidone versus clozapine in the treatment of psychotic symptoms in Parkinson disease: a randomized open clinical trial. Clin Neuropharmacol. 2012;35(2):61–6. [DOI] [PubMed] [Google Scholar]
  • 93.Friedman JH. Melperone is ineffective in treating Parkinson’s disease psychosis. Mov Disord. 2012;27(6):803–4. [DOI] [PubMed] [Google Scholar]
  • 94.Leroi I, et al. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson’s disease. Int J Geriatr Psychiatry. 2004;19(1):1–8. [DOI] [PubMed] [Google Scholar]
  • 95.Emre M, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24):2509–18. [DOI] [PubMed] [Google Scholar]
  • 96.McKeith IG, et al. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. 2000;54(5):1050–8. [DOI] [PubMed] [Google Scholar]
  • 97.Sawada H, Oeda T. Protocol for a randomised controlled trial: efficacy of donepezil against psychosis in Parkinson’s disease (EDAP). BMJ Open. 2013;3(9):e003533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Boot BP. Comprehensive treatment of dementia with Lewy bodies. Alzheimers Res Ther. 2015;7(1):45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Nicholson SL, Brotchie JM. 5-hydroxytryptamine (5-HT, serotonin) and Parkinson’s disease: opportunities for novel therapeutics to reduce the problems of levodopa therapy. Eur J Neurol. 2002;9(Suppl 3):1–6. [DOI] [PubMed] [Google Scholar]
  • 100.Zoldan J, et al. Psychosis in advanced Parkinson’s disease: treatment with ondansetron, a 5-HT3 receptor antagonist. Neurology. 1995;45(7):1305–8. [DOI] [PubMed] [Google Scholar]
  • 101.Meltzer HY, et al. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacology. 2010;35(4):881–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 102.Cummings J, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533–40. [DOI] [PubMed] [Google Scholar]
  • 103.Voon V, Lang AE. Antidepressants in the treatment of psychosis with comorbid depression in Parkinson disease. Clin Neuropharmacol. 2004;27(2):90–2. [DOI] [PubMed] [Google Scholar]
  • 104.Godschalx-Dekker JA, Siegers HP. Reduction of parkinsonism and psychosis with mirtazapine: a case report. Pharmacopsychiatry. 2014;47(3):81–3. [DOI] [PubMed] [Google Scholar]
  • 105.Meco G, Bernardi S. Antidepressant use in treatment of psychosis with comorbid depression in Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(1):311–3. [DOI] [PubMed] [Google Scholar]
  • 106.Hurwitz TA, Calne DB, Waterman K. Treatment of dopaminomimetic psychosis in Parkinson’s disease with electroconvulsive therapy. Can J Neurol Sci. 1988;15(1):32–4. [DOI] [PubMed] [Google Scholar]
  • 107.McGorry PD. Psychoeducation in first-episode psychosis: a therapeutic process. Psychiatry. 1995;58(4):313–28. [DOI] [PubMed] [Google Scholar]
  • 108.Pacchetti C, et al. Active music therapy in Parkinson’s disease: an integrative method for motor and emotional rehabilitation. Psychosom Med. 2000;62(3):386–93. [DOI] [PubMed] [Google Scholar]
  • 109.US FDA. FDA approves first drug to treat hallucinations and delusions associated with Parkinson’s disease. 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm498442.htm. [Google Scholar]

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