The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Trial of Pimavanserin in Dementia-Related Psychosis
Open accessAbstract
BACKGROUND: inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis. RESULTS: Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin. CONCLUSIONS: In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An RCT of pimavanserin (an atypical antipsychotic with selective serotonin 5-HT2a inverse agonist effect) withdrawal in dementia-related psychosis was stopped early due to lower rates of relapse in the treatment versus placebo groups, which appeared to be driven by effects in people with Parkinson's disease .(538)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [538]
Experimental — accuracy not yet measuredIn the citing paper
“Pimavanserin (Nuplazid) Inverse agonist and antagonist of 5-HT2A in neurotransmission Completed phase 2 (2017–2019) Probable AD who has symptoms of agitation and aggression (1) Promising reduction of psychosis score in AD, also see [ 74 ] and (2) delay in psychosis relapse ( p < 0.05) and a lower risk of relapse with the continuation of the drug [ 75 ] 03118947 03325556”
From Current therapeutics for Alzheimer’s disease and clinical trials (2024) · cites this paper as [74]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657
(1976) · Medical Entomology and Zoology · Cited by 8,899
Relatives of the Impaired Elderly: Correlates of Feelings of Burden
Zarit, S. H., Reever, K. E., & Bach-Peterson, J. (1980) · The Gerontologist · doi:10.1093/geront/20.6.649 · Cited by 5,810
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., et al. (2011) · Brain · doi:10.1093/brain/awr179 · Cited by 5,221
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187889.17253.b1 · Cited by 5,069
Self-citationSubjective and objective sleepiness in the active individual
Åkerstedt, T., & Gillberg, M. (1990) · International Journal of Neuroscience · doi:10.3109/00207459008994241 · Cited by 3,088
Clinical diagnostic criteria for dementia associated with Parkinson’s disease
Emre, M., Aarsland, D., Brown, R., Burn, D. J., Duyckaerts, C., Mizuno, Y., Broe, G. A., Cummings, J., Dickson, D. W., Gauthier, S., et al. (2007) · Movement Disorders · doi:10.1002/mds.21507 · Cited by 3,027
Self-citationThe Robust Inference for the Cox Proportional Hazards Model
Lin, D. Y., & Wei, L. J. (1989) · Journal of the American Statistical Association · doi:10.1080/01621459.1989.10478874 · Cited by 2,695
Scale for Assessment of Positive Symptoms (SAPS) 1984
Andreasen, N. C. (1995) · Open Scholarship Institutional Repository (Washington University in St. Louis) · Cited by 2,423
Cummings, J. L., Isaacson, S., Mills, R., Williams, H., Chi‐Burris, K., Corbett, A., Dhall, R., & Ballard, C. G. (2013) · The Lancet · doi:10.1016/s0140-6736(13)62106-6 · Cited by 954
Self-citationDiagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement
Sachdev, P., Kalaria, R., O’Brien, J., Skoog, I., Alladi, S., Black, S. E., Blacker, D., Blazer, D. G., Chen, C., Chui, H., et al. (2014) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000034 · Cited by 852
Predictors of Nursing Home Placement in Parkinson's Disease: A Population‐Based, Prospective Study
Aarsland, D., Larsen, J. P., Tandberg, E., & Laake, K. (2000) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2000.tb06891.x · Cited by 811
Gale, S. A., Acar, D., & Daffner, K. R. (2018) · The American Journal of Medicine · doi:10.1016/j.amjmed.2018.01.022 · Cited by 788
Reus, V. I., Fochtmann, L. J., Eyler, A. E., Hilty, D. M., Horvitz-Lennon, M., Jibson, M. D., Lopez, O. L., Mahoney, J., Pasic, J., Tan, Z. S., et al. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.173501 · Cited by 441
Manual for the Extrapyramidal Symptom Rating Scale (ESRS)
Chouinard, G., & Margolese, H. C. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2005.02.013 · Cited by 424
Peters, M. E., Schwartz, S., Han, D., Rabins, P. V., Steinberg, M., Tschanz, J. T., & Lyketsos, C. G. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14040480 · Cited by 400
On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis
Hacksell, U., Burstein, E. S., McFarland, K., Mills, R., & Williams, H. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1293-3 · Cited by 302
Lyketsos, C. G., Colenda, C. C., Beck, C. M., Blank, K., Doraiswamy, M. P., Kalunian, D. A., & Yaffe, K. S. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000221334.65330.55 · Cited by 274
Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses
Tampi, R. R., Tampi, D. J., Balachandran, S., & Srinivasan, S. (2016) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622316658463 · Cited by 267
Relapse Risk after Discontinuation of Risperidone in Alzheimer's Disease
Devanand, D. P., Mintzer, J. E., Schultz, S. K., Andrews, H., Sultzer, D. L., de la Pena, D., Gupta, S., Colon, S., Schimming, C., Pelton, G. H., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1114058 · Cited by 196
Self-citationBallard, C. G., Bannister, C., Khan, Z., Cummings, J. L., Demos, G., Coate, B., Youakim, J. M., Owen, R., Stankovic, S., Tomkinson, E. B., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30039-5 · Cited by 195
Self-citationMintzer, J. E., Tune, L. E., Breder, C. D., Swanink, R., Marcus, R. N., McQuade, R. D., & Forbes, A. (2007) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181557b47 · Cited by 157
Tariot, P. N., Schneider, L. S. S., Katz, I. R., Mintzer, J. E., Street, J. S., Copenhaver, M. D., & Williams-Hughes, C. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000196628.12010.35 · Cited by 146
Self-citationDeberdt, W. G., Dysken, M. W., Rappaport, S. A., Feldman, P. D., Young, C. A., Hay, D. P., Lehman, D. L., Dossenbach, M. R. K., Degenhardt, E. K., & Breier, A. F. (2005) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200508000-00012 · Cited by 129
Mintzer, J., Greenspan, A., Caers, I., Van Hove, I., Kushner, S., Weiner, M., Gharabawi, G., & Schneider, L. S. (2006) · The American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000194643.63245.8c · Cited by 94
Brief Psychosocial Therapy for the Treatment of Agitation in Alzheimer Disease (The CALM-AD Trial)
Ballard, C. G., Brown, R. G., Fossey, J., Douglas, S., Bradley, P., Hancock, J., James, I. A., Juszczak, E., Bentham, P., Burns, A. S., et al. (2009) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181b0f8c0 · Cited by 86
Self-citationEspay, A. J., Guskey, M. T., Norton, J. C., Coate, B., Vizcarra, J. A., Ballard, C. G., Factor, S. A., Friedman, J. H., Lang, A. E., Larsen, N. J., et al. (2018) · Movement Disorders · doi:10.1002/mds.27488 · Cited by 56
Self-citationCerebral correlates of psychotic syndromes in neurodegenerative diseases
Jellinger, K. A. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01311.x · Cited by 43
Vernon, E. K., Cooley, B., Rozum, W., Rattinger, G. B., Behrens, S., Matyi, J., Fauth, E. B., Lyketsos, C. G., & Tschanz, J. T. (2018) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2018.11.010 · Cited by 40
Lornstad, M. T., Aarøen, M., Bergh, S., Benth, J. Š., & Helvik, A.-S. (2019) · BMC Geriatrics · doi:10.1186/s12877-019-1126-y · Cited by 24
Cited by
Sorted by citations
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
Livingston, G., Huntley, J., Liu, K. Y., Costafreda, S. G., Selbæk, G., Alladi, S., Ames, D., Banerjee, S., Burns, A., Brayne, C., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01296-0 · Cited by 3,860
The neuropsychiatry of Parkinson's disease: advances and challenges
Weintraub, D., Aarsland, D., Chaudhuri, К. R., Dobkin, R. D., Leentjens, A. F. G., Rodriguez-Violante, M., & Schrag, A. E. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00330-6 · Cited by 480
Self-citationTanner, C. M., & Ostrem, J. L. (2024) · New England Journal of Medicine · doi:10.1056/nejmra2401857 · Cited by 438
Medical, surgical, and physical treatments for Parkinson's disease.
Foltynie, T., Bruno, V., Fox, S. H., Kühn, A., Lindop, F., & Lees, A. (2024) · The Lancet · doi:10.1016/s0140-6736(23)01429-0 · Cited by 197
Dementia Prevention and Treatment
Reuben, D. B., Kremen, S. A., & Maust, D. T. (2024) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2023.8522 · Cited by 225
Metadata
- Authors
- Tariot, P. N., Cummings, J. L., Soto-Martin, M. E., Ballard, C., Erten-Lyons, D., Sultzer, D. L., Devanand, D. P., Weintraub, D., McEvoy, B., Youakim, J. M., Stankovic, S., & Foff, E. P.
- Affiliations
- University of Nevada, Las Vegas (US)
- From Banner Alzheimer’s Institute and University of Arizona College of Medicine, Phoenix (P.N.T.); Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.); Gérontopôle Alzheimer Clinical and Research Center, Centre Hospitalier Universitaire de Toulouse, Geriatric Department, Maintain Functions and Intrinsic Capacities with Aging Research Team, Center for Epidemiology and Population Health Research, INSERM, Université Paul Sabatier, Toulouse, France (M.E.S.-M.); University of Exeter School of Medicine, Exeter, United Kingdom (C.B.); the Department of Neurology, Oregon Health and Sciences University, Portland (D.E.-L.); the Department of Psychiatry and Human Behavior and the Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine (D.L.S.), and Acadia Pharmaceuticals, San Diego (B.M., J.M.Y., S.S., E.P.F.) — both in California; the Department of Ps...
- Acadia Pharmaceuticals (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-07-22
- Volume
- 385
- Issue
- 4
- Pages
- 309-319
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3184254488
- Cited by
- 145
- References
- 31
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 37 · 2023: 24 · 2022: 29 · 2021: 9
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Figshare (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- ACADIA Pharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- pimavanserin, dementia-related psychosis, Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, relapse, delusions and hallucinations, antipsychotic withdrawal, adverse events, QT prolongation, drug discontinuation
- MeSH terms
- Aged, Aged, 80 and over, Dementia, Double-Blind Method, Female, Hallucinations, Humans, Male, Middle Aged, Parkinson Disease, Piperidines, Psychotic Disorders, Recurrence, Antipsychotic Agents, Urea, Proportional Hazards Models, Kaplan-Meier Estimate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
