Neurology Case Challenge: Visual and Auditory Hallucinations in a Patient With Parkinson Disease

Lee Neilson, MD; Elena Cecilia Rosca, MD, PhD; Simu Mihaela, MD, PhD; Chirileanu Ruxanda Dana, MD, PhD


January 24, 2022

In this patient, the cognitive impairments and neuropsychiatric symptoms (hallucinations, cognition fluctuations) were treated with donepezil 10 mg at bedtime. Acetylcholinesterase inhibitors are useful in treating the cognitive deficits of DLB. Robust evidence supports the efficacy of rivastigmine and donepezil; however, high-quality randomized controlled studies of galantamine are lacking. The evidence for adding mematine, an N-methyl D-asparatate receptor antagonist, is mixed.[18] Investigators reported that this agent appeared to improve global clinical status and behavioral symptoms of patients with mild to moderate DLB. Compared with patients who received placebo, a higher proportion of patients with PDD and DLB who were treated with memantine showed improvement or stabilization in their clinical global status (Alzheimer's Disease Cooperative Study-clinical global impression of change [ADCS-CGIC] scores) at the end of the study.[19] Mean neuropsychiatric inventory (NPI) total scores were also significantly higher in patients with DLB who received memantine, including single-item scores for delusions, hallucinations, sleeping or night-time behavior, and appetite or eating disorder. However, no significant differences were seen in any of the cognitive tests in patients with PDD at the end of the study. The incidence of adverse events and drug discontinuation was similar between the PDD or DLB treatment and placebo groups. The most common adverse event associated with memantine treatment compared with placebo was somnolence. The most common serious adverse events reported were stroke, falls, and worsening dementia.

The patient in this case also received quetiapine 25 mg/day for depression and hallucinations. Data are limited regarding the treatment of depression in DLB; however, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) appear to be effective and tolerated well. Typical neuroleptics (eg, haloperidol) should be avoided in the treatment of psychosis, given the sensitivity of these patients to neuroleptics and the increased risk for neuroleptic malignant syndrome.[21] When psychosis is severe or distressing, atypical neuroleptics are preferred if a cholinesterase inhibitor is insufficient. Quetiapine is relatively safe. Clozapine may be more effective, but its use mandates hematologic monitoring.[22] Pimavanserin, a serotonin receptor modulator, is currently approved only for Parkinson disease psychosis. However, one phase 3 study showed that it was effective at preventing psychosis relapse in undifferentiated dementia; 7.1% of participants in that group had DLB.[23] A similar study comparing the efficacy of pimavanserin to quetiapine is underway in Parkinson disease.[24]


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