Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management

John O'Brien, John Paul Taylor, Clive Ballard, Roger A Barker, Clare Bradley, Alistair Burns, Daniel Collerton, Sonali Dave, Rob Dudley, Paul Francis, Andrea Gibbons, Kate Harris, Vanessa Lawrence, Iracema Leroi, Ian McKeith, Michel Michaelides, Chaitali Naik, Claire O'Callaghan, Kirsty Olsen, Marco Onofrj, Rebecca Pinto, Gregor Russell, Peter Swann, Alan Thomas, Prabitha Urwyler, Rimona Sharon Weil, Dominic Ffytche, John O'Brien, John Paul Taylor, Clive Ballard, Roger A Barker, Clare Bradley, Alistair Burns, Daniel Collerton, Sonali Dave, Rob Dudley, Paul Francis, Andrea Gibbons, Kate Harris, Vanessa Lawrence, Iracema Leroi, Ian McKeith, Michel Michaelides, Chaitali Naik, Claire O'Callaghan, Kirsty Olsen, Marco Onofrj, Rebecca Pinto, Gregor Russell, Peter Swann, Alan Thomas, Prabitha Urwyler, Rimona Sharon Weil, Dominic Ffytche

Abstract

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson's disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.

Keywords: dementia; hallucinations; parkinson's disease.

Conflict of interest statement

Competing interests: Roger A Barker has acted as a consultant to UCB, Living Cell Technologies, BlueRock Therapeutics, Sana Biotechnology, FCDI, Novo Nordisk and Cellino. Clare Bradley is director and majority shareholder of Health Psychology Research Ltd, which licences her patient-reported outcome measures for others to use and manages their linguistic validation into other languages. She receives royalties when existing language versions of her questionnaires are licensed to commercial companies. Her College currently receives research grants to support her research from ViiVHealthCare and from Medtronic. She has recently received speaker fees from Astellas and routinely advises many pharmaceutical companies and contract research organisations on the use of her questionnaires in their clinical trials. Robert Dudley reports delivering training workshops and has written books about CBT, for which he has received fees, and reports delivering CBT in the National Health Service (NHS). Paul Francis has received speaking fees from Suven and Nutricia. Iracema Leroi has received speaking fees from Eisai, Boehringer Ingelheim, GE Healthcare, GlaxoSmithKline, Shire and Lundbeck. Ian McKeith has acted as a consultant for GE Healthcare, Sumitomo Dainippon Pharma, Sanofi and Eisai. John O’Brien has acted as a consultant for TauRx, Axon, GE Healthcare and Eisai. Marco Onofrj has served on the scientific advisory boards of GlaxoSmithKline, Novartis, Lundbeck, Eisai, Valeant, Medtronic and Newron; has received speaker honoraria from Zambon, the World Parkinson Congress, the Movement Disorder Society and the Atypical Dementias congress; was an invited guest and lecturer for the Mental Disorders in Parkinson Disease Congress; serves on the editorial board of Medicine (Baltimore); has been employed as a speaker for Boehringer Ingelheim, GlaxoSmithKline, UCB and Zambon and has received research support from the Italian Ministry of Health and the Italian Ministry of Education. Rimona S Weil has received speaker fees from GE Healthcare. John-Paul Taylor has received speaker fees from GE Healthcare and acted as a consultant for Heptares-Sosei. No other authors declared any conflicts.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
The consensus framework for the management of visual hallucinations in different conditions. Recommendations not supported by meta-analysis are indicated in white. Orange boxes indicate hallucination characteristics and therapeutic targets.AD, Alzheimer’s disease; CBS, Charles Bonnet syndrome; CBT, cognitive behavioural therapy; DLB, dementia with Lewy bodies;PD, Parkinson’s disease; PDD, PD dementia.

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