Pimavanserin in Alzheimer's Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms
Open accessAbstract
BACKGROUND: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. OBJECTIVE: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer's disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Nursing home residents. PARTICIPANTS: Patients with AD psychosis. INTERVENTIONS: Pimavanserin 34 mg or placebo daily for 12 weeks. MEASUREMENTS: The primary endpoint was mean change from baseline at Week 6 on the Neuropsychiatric Inventory-Nursing Home Version psychosis score (NPI-NH-PS). In the prespecified subgroup analysis, the mean change in NPI-NH-PS and the responder rates among those with baseline NPI-NH-PS ≥12 were evaluated. RESULTS: Of 181 patients randomized (n=90 pimavanserin; n=91 placebo), 57 had baseline NPI-NH-PS ≥12 (n=27 pimavanserin; n=30 placebo). In this severe subgroup, large treatment effects were observed (delta=-4.43, Cohen's d=-0.73, p=0.011), and ≥30% improvement was 88.9% vs. 43.3% (p<0.001) and ≥50% improvement was 77.8% vs. 43.3% (p=0.008) for pimavanserin and placebo, respectively. The rate of adverse events (AEs) in the severe subgroup was similar between treatment groups, and urinary tract infection, fall, and agitation were most frequent. Serious AEs was similar with pimavanserin (17.9%) and placebo (16.7%) with fewer discontinuations due to AEs with pimavanserin (7.1%) compared to placebo (10.0%). Minimal change from baseline occurred for the mean MMSE score over 12 weeks. CONCLUSIONS: Pimavanserin demonstrated significant efficacy in AD psychosis in patients with higher baseline severity of psychotic symptoms (NPI-NH-PS ≥12). Treatment with pimavanserin showed an acceptable tolerability profile.
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An earlier RCT of pimavanserin efficacy in AD psychosis showed differences favouring pimavanserin at week 6 but not at 2, 4, 9 or 12 weeks.
“An earlier RCT of efficacy in AD psychosis showed differences favouring pimavanserin at week 6 but not at 2, 4, 9 or 12 weeks.(540)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [540]
The Study Design and Discussion describe a randomized placebo-controlled trial and report efficacy in the overall AD-psychosis population at week 6. The Discussion also says the difference from placebo was not significant at week 12 in the more-severe subgroup. Our copy does not establish the claimed lack of differences at weeks 2, 4, or 9, or a week-12 result for the overall population. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA pooled analysis of RCTs of risperidone using the CMAI (n=1150) showed a mean dose of 1mg/day was associated with an improvement of -5.4 CMAI points at 12 weeks.
“In comparison, a pooled analysis of RCTs of risperidone that used the CMAI (n=1150) showed a mean dose of 1mg/day was associated with an improvement of -5.4 CMAI points at 12 weeks.(545)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [545]
The Methods (Study Assessments; page unavailable) mention the CMAI-Short Form, but the paper reports a pimavanserin-versus-placebo study, not a pooled analysis of risperidone trials. Searches for risperidone, the pooled analysis, and the claimed dose and CMAI change found no passage supporting the cited result. (LLM, conf=0.76)
Experimental — accuracy not yet measuredRisperidone remains the atypical antipsychotic with the largest RCT evidence base in the treatment of agitation.
“Risperidone remains the atypical antipsychotic with the largest RCT evidence base in the treatment of agitation.”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [545]
The background passage on antipsychotics discusses randomized trials for psychosis generally, and the Discussion reports a pimavanserin analysis in patients with Alzheimer’s disease psychosis. Searches for risperidone and comparative RCT evidence found no passage saying that risperidone has the largest RCT evidence base for treating agitation. No page numbers were available in the indexed passages. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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- Authors
- Ballard, C., Youakim, J. M., Coate, B., & Stankovic, S.
- Affiliations
- University of Exeter (GB)
- Acadia Pharmaceuticals (United States) (US)
- Corresponding author
- Ballard, Clive
- Venue
- The Journal of Prevention of Alzheimer's Disease
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 6
- Issue
- 1
- Pages
- 27-33
- ISSN
- 2274-5807 (ISSN-L)
- PMC
- PMC12280763
- OpenAlex
- W2889633769
- Cited by
- 40
- References
- 28
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 8 · 2018: 2
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The Journal of Prevention of Alzheimer s Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Pfizer
- GlaxoSmithKline
- ACADIA Pharmaceuticals
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- pimavanserin, 5-HT2A receptor antagonist, inverse agonists, nursing home residents, treatment efficacy, tolerability, adverse events, urinary tract infection, falls
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Double-Blind Method, Female, Humans, Male, Middle Aged, Nursing Homes, Piperidines, Psychotic Disorders, Urea, Treatment Outcome, Serotonin 5-HT2 Receptor Antagonists
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