Parkinson's disease, visual hallucinations and apomorphine: A review of the available evidence

Borgemeester, Robbert W K; Lees, Andrew J.; Laar, Teus van

doi:10.1016/j.parkreldis.2016.04.023

Cited by 46 publications

(34 citation statements)

References 94 publications

(146 reference statements)

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“…The chemical structure of apomorphine includes a piperidine moiety and, unlike other dopamine agonists, this drug exerts intrinsic antagonist effects at the 5-HT 2A receptor as well as agonist affects at both D1-like and D2-like receptors 148 . This unique profile might account for case report and open-label study evidence that apomorphine does not exacerbate psychosis symptoms and, in some studies, may ameliorate these symptoms 149 or improve visual contrast sensitivity 150 .…”

Section: Treatmentmentioning

confidence: 99%

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The psychosis spectrum in Parkinson disease

et al. 2017

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In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors — for example, autonomic dysfunction — that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.

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Section: Treatmentmentioning

confidence: 99%

“…The effect size for apomorphine (0.32) was larger than for intrajejunal levodopa (0.29), although the difference was not significant 152 . Apomophine might have a place in the treatment of PD psychosis; however, a better evidence base is needed to guide future recommendations 148,152,153 .…”

Section: Treatmentmentioning

confidence: 99%

The psychosis spectrum in Parkinson disease

et al. 2017

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“…Similar data were found for users of dopamine agonists in a meta-analysis and review studies. 41,42 Based in the context of drug-induced visual hallucinations in Parkinson's disease patients, magnetic resonance imaging studies have suggested the importance of dopamine in the development of visual hallucations, showing that PD patients frequently display progressive atrophy in the paralimbic, limbic, and neocortical areas, as well as in cerebral areas in which dopamine is the main neurotransmitter. 43 In contrast, we observed a protective effect in the occurrence of visual hallucinations in users of entacapone and amantadine, after the analyses of the multiple Poisson regression.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease

Santos

Duarte

Miranda

et al. 2019

The Journal of Clinical Pharma

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Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile of Parkinson's disease patients seem to influence the occurrence of visual hallucinations. In our study, we investigated a possible relationship of sequence variants in DRD1, DRD2, DRD3, DAT1, and COMT genes with the presence of visual hallucinations in Parkinson's disease patients. A total of 224 Brazilian patients from the Pro-Parkinson service at the Clinical Hospital of the University of Pernambuco, diagnosed with sporadic Parkinson's disease, were enrolled. Parkinson's disease patients were divided into 2 groups based on the presence or absence of visual hallucinations. The sequence variants for DRD1, DRD2, DRD3, DAT1, and COMT were determined through the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple Poisson regression analyses showed that individuals carrying the DRD3 Ser/Ser and Ser/Gly genotypes presented increased prevalence ratios of visual hallucinations (9.7-fold and 4.4-fold, respectively; P < .001). Regarding DAT1 rs28363170, there was a 9.82-fold increase in the prevalence ratio in patients with the 10/11 genotype, 8.78-fold for the 10/8 genotype, and 2.44-fold for the 9/8 genotypes (P < .001, for all). In addition, visual hallucinations were also associated with use of transdermal patches with rotigotine (PR, 3.7; 95%CI, 1.2-10.9; P = .017) and rasagiline (PR, 2.8; 95%CI, 1.3-6.0; P = .006). Our results suggest that the genetic variants DRD3 and DAT1, along with other therapeutic confounders, may influence the prevalence ratio of visual hallucinations.

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“…This is based on the hallucinogenic potency of 5-HT 2A receptor agonists, such as psilocybin, mescaline and Lysergic acid diethylamide (LSD). Additionally, apomorphine has been suggested to treat visual hallucinations as a 5-HT 2A receptor antagonist in Parkinson’s disease (PD) 4. The role of the 5-HT 2A receptor in visual hallucinations in PD is supported by positron emission tomography (PET) studies comparing patients with PD with and without visual hallucinations, demonstrating an increased 5-HT 2A binding in the prefrontal and visual processing areas of the hallucinating patients 4 5…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of intractable visual hallucinations with 5-HT_{_2A}antagonist ketanserin

Sommer¹,

Kleijer

Visser

et al. 2018

BMJ Case Reports

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Hallucinations, visual, auditory or in another sensory modality, often respond well to treatment in patients with schizophrenia. Some, however, do not and can be very chronic and debilitating. We present a patient with schizophrenia with intractable hallucinations despite state of the art care, including high-dose clozapine and transcranial magnetic stimulation. Based on the possible role of the 5-HT receptor in hallucinations, we treated her with the antihypertensive drug ketanserin, a 5-HT receptor antagonist.This significantly reduced her visual but not her auditory hallucinations, suggesting a possible role of the 5HT receptor in the pathophysiology of specifically visual hallucinations. This is the first time ketanserin has been described to successfully reduce visual hallucinations in a patient with schizophrenia.

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Parkinson's disease, visual hallucinations and apomorphine: A review of the available evidence

Abstract: Background

Cited by 46 publications

References 94 publications

The psychosis spectrum in Parkinson disease

The psychosis spectrum in Parkinson disease

Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease

Successful treatment of intractable visual hallucinations with 5-HT_{_2A}antagonist ketanserin

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Parkinson's disease, visual hallucinations and apomorphine: A review of the available evidence

Abstract: Background

Cited by 46 publications

References 94 publications

The psychosis spectrum in Parkinson disease

The psychosis spectrum in Parkinson disease

Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease

Successful treatment of intractable visual hallucinations with 5-HT2Aantagonist ketanserin

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Product

Resources

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Successful treatment of intractable visual hallucinations with 5-HT_{_2A}antagonist ketanserin