The Lewy Body Dementia Association is deeply concerned about the recent ruling by the FDA in which it rejected ACADIA Pharmaceutical’s supplemental new drug application for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis.
Visual hallucinations occur in up to 80% of people with LBD and delusions in up to 50%; these symptoms are often distressing to both the person with LBD and their primary caregiver. In a study comparing AD and DLB caregiver, only DLB caregivers had high distress, which was driven by hallucinations, delusions, anxiety and apathy. Psychosis may even present before the onset of dementia in DLB; as such, one possible prodrome of DLB being explored is “psychiatric-onset DLB.” 
Psychosis is especially challenging to manage in LBD: up to 50% of people with DLB may have a severe negative reaction to any form of antipsychotic medication and particularly those which act by blocking dopamine receptors. While the mainstay treatments are off-label use of cholinesterase inhibitors, quetiapine, and clozapine which requires weekly blood monitoring, clinical trials have not shown efficacy and a significant proportion of patients experience side effects which limit their clinical utility. Atypical antipsychotics with high D2 receptor antagonism (such as olanzapine and risperidone), should be avoided due to the risk of severe neuroleptic sensitivity reactions, neuroleptic malignant syndrome, worsening parkinsonism, somnolence and orthostatic hypotension.
LBD families currently have little option but to accept substantial risk of side effects from existing treatments, risks that may seem smaller compared to challenges with safety and providing care for a person with difficult behavioral changes. In a recent article by two members of LBDA’s Scientific Advisory Council, Daniel Weintraub, MD and Melissa Armstrong, MD, MSc, FAAN included quotes from LBD caregivers participating in LBDA’s online forums to support the case for antipsychotics in DLB despite the potential risk for adverse effects:
“At this point, I am willing to try anything just to keep him safe from hurting himself or anyone else. I hate the feeling of being scared to death of him.”
“Risperdal is the only thing that worked… It is on the no-no list for LBD, but her psychosis got so bad without it that it affected her physical health and well-being….”
LBD families also face considerable challenges in access to long term care, both at time of admission and from unanticipated discharge. Some long-term care facilities prohibit admission of people with an LBD simply based on their diagnosis, to avoid caring for a person who may have behavioral changes. For companies that do admit people with LBD, there is a considerable risk of involuntary discharge due to insufficient clinical management of hallucinations and delusions, or if staffing levels and/or training is inadequate to provide person-centered care in response to behavioral changes.
In summary, people with LBD and family caregivers are facing extensive burden from the currently inadequate options for clinical management of hallucinations and delusions, starting as early as the prodromal stage of the disease. Improved therapeutics for hallucinations and delusions are urgently needed by people with LBD and their families, and in fact, have been eagerly awaited.
 Ricci M, Guidoni SV, Sepe-Monti M, et al. Clinical findings, functional abilities and caregiver distress in the early stage of dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Archives of Gerontology and Geriatrics. 2009;49:e101–e104.
 McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020:94(7);1-13
 Stinton C, McKeith I, Taylor J-P, et al. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2015;172:731–742.
 1. Armstrong MJ, Weintraub D. The Case for Antipsychotics in Dementia with Lewy Bodies. Mov Disord Clin Pract. 2016;4:32–35.