March 18, 2024
Hallucinations and delusions (also called psychosis) are prominent features of Lewy body dementia (LBD), occurring in both dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). The FDA recently approved a change to the prescribing label for pimavanserin, a drug previously approved for psychosis in Parkinson’s disease. The new label makes it clear that pimavanserin is FDA-approved for treatment of psychosis in Parkinson’s disease dementia.
The label change is supported by data from the HARMONY study of pimavanserin in dementia-related psychosis, a Phase 3 clinical trial of nearly 400 people. The full results of the HARMONY trial were published previously. The HARMONY study was a rare example of a trial stopped early for efficacy—this means the drug worked so well that it was considered unethical to continue the trial because some people were on placebo. Of the 392 participants in HARMONY, 59 had PDD, and the results from this group have recently been published. The lead author is Dr. Daniel Weintraub, an investigator at the University of Pennsylvania LBDA Research Center of Excellence. Of the 59 participants with PDD, 30 received either pimavanserin (13) or a placebo (17). At the end of the trial, 9 of the 17 receiving placebo had relapsed, but only 1 of the 13 receiving pimavanserin had relapsed. Although the number of people in each group was relatively small, this represents a 95% reduced risk of relapse in the group taking pimavanserin. Moreover, the medication was well tolerated and did not lead to any worsening of motor or cognitive function.
While there were participants with DLB in the trial, the size of this group was too small to do a subgroup analysis. There are currently no medications FDA-approved for the treatment of psychosis in DLB. For treatment of hallucinations and delusions in DLB, clinicians must prescribe treatments ‘off-label,’ such as the antipsychotic medications quetiapine, pimavanserin, clozapine, and olanzapine, or acetylcholinesterase inhibitors such as donepezil, rivastigmine, or galantamine.
Participating in research is one of the most important things a person with LBD and their care partners can do to advance treatment options for the future. LBDA encourages you to learn more about currently recruiting clinical trials and other studies by visiting our clinical trials page. And if you would like to be alerted when new studies become available, please consider signing up for the Lewy Trial Tracker.
REFERENCES
Weintraub D,j.parkreldis.2019.11.009 al. 2024. Pimavanserin for psychosis in Parkinson’s disease dementia: Subgroup analysis of the HARMONY Trial. Parkinsonism and Related Disorders, 119. DOI: 10.1016/j.parkreldis.2023.105951 (doi.org)
Tariot PN, Cummings JL, Soto-Martin ME, et al. 2021. Trial of Pimavanserin in Dementia-Related Psychosis. New England Journal of Medicine, 385. DOI: 10.1056/NEJMoa2034634 (doi.org)
Horn S, Richardson H, Xie SX, et al. 2019. Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson’s disease and dementia with Lewy bodies. Parkinsonism and Related Disorders, 69. DOI:10.1016/j.parkreldis.2019.11.009 (doi.org)