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pimavanserin (Nuplazid)

Indications: - psychosis (hallucinations & delusions) associated with Parkinson's disease [1,2] & diffuse Lewy body disease [5] - induces & maintains remission in dementia-related psychosis [7] - add-on treatment of schizophrenia negative symptoms [6] Contraindications: - treatment of hallucinations & delusions in Alzheimer's disease [11] Dosage: - 34 mg PO QD Tablets: 17 mg * mix with soft food [9] Pharmacokinetics: - CYP3A4 substrate Adverse effects: - overall, well tolerated [1,12] - does not worsen motor symptoms (parkinsonism) [12] - does not worsen cognitive symptoms in patients with Parkinson's disease [12] - pedal edema - nausea - confusion - increased risk of 30-day hospitalization [10] - increased risk of death persisting up to 1 year [10] Boxed Warning: - increased risk of death associated with the use to treat older people with dementia-related psychosis [2] - may be used in patients with Parkinson's disease-related hallucinations & delusions with dementia [2] - 600 reported deaths associated with the drug in 2017 [4] Drug interactions: - dosage reduction may be needed with strong CYP3A4 inhibitors - dosage increase may be needed with strong CYP3A4 inducers Mechanism of action: - selective serotonin 5-HT2A receptor antagonist Clinical trials: 1) in a trial stopped early for efficacy, patients with dementia-related psychosis with response to pimavanserin had lower risk of relapse with continuation of pimavanserin than discontinuation [8]

Interactions

drug adverse effects of antipsychotic agents

General

serotonin antagonist antipsychotic agent

Database Correlations

PUBCHEM correlations

References

  1. Cummings J et al Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. The Lancet, Early Online Publication, 1 November 2013 PMID: 24183563 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62106-6/abstract
  2. FDA News Release. April 29, 2016 FDA approves first drug to treat hallucinations and delusions associated with Parkinson's disease. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm498442.htm - Acadia Pharmaceuticals Label Update for NUPLAZID (pimavanserin). Sept 18, 2023 https://acadia.com/media/news-releases/acadia-pharmaceuticals-announces-label-update-for-nuplazid-pimavanserin/
  3. Windle ML FDA Drug Approvals and Changes: May edition. Medscape. May 20, 2016 http://reference.medscape.com/features/slideshow/drug-review/2016/may
  4. NEJM JWatch Editors New Parkinson's Drug Under Scrutiny Over Safety Concerns Physician's First Watch, April 27, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Ellis B, Hicken M FDA re-examines safety of controversial new drug. CNN Health. April 25, 2018 https://www.cnn.com/2018/04/25/health/fda-nuplazid-safety-evaluation-invs/index.html
  5. Velayudhan L, Ffytche D, Ballard C, Aarsland D. New Therapeutic Strategies for Lewy Body Dementias. Curr Neurol Neurosci Rep. 2017 Sep;17(9):68. Review. PMID: 28741230
  6. Monaco K Add-On Nuplazid Gets a Win in Early Schizophrenia Trial - Phase II study met primary efficacy endpoint. MedPage Today September 11, 2020 https://www.medpagetoday.com/meetingcoverage/psychcongress/88578 - Bugarski-Kirola D et al ADVANCE: Phase 2, randomized, double-blind, placebo-controlled study of adjunctive pimavanserin in patients with negative symptoms of schizophrenia. Psych Congress 2020; Poster #106.
  7. Monaco K Trial: Drug Induces, Maintains Dementia-Related Psychosis Remission - Results pave way for Nuplazid label expansion. MedPage Today September 14, 2020 https://www.medpagetoday.com/meetingcoverage/psychcongress/88607 - Foff E, et al Pimavanserin significantly reduces risk of relapse of dementia-related psychosis: results from the double-blind phase of the HARMONY study. Psych Congress 2020; Poster #187 Foff E, et al Response to pimavanserin treatment in patients with dementia-related psychosis: results From the 12-week, open-label phase of the HARMONY study. Psych Congress 2020; Poster #197
  8. Grant K Staying on Pimavanserin Cut Dementia-Related Psychosis Relapse. However, late-stage trial couldn't separate efficacy in dementia subtypes. MedPage Today July 21, 2021 https://www.medpagetoday.com/psychiatry/dementia/93689 - Tariot PN, Cummings JL, Soto-Martin ME et al Trial of pimavanserin in dementia-related psychosis. N Engl J Med 2021; 385:309-319, July 22 PMID: 34289275 https://www.nejm.org/doi/full/10.1056/NEJMoa2034634 - Friedman JI Pimavanserin in dementia-related psychosis. N Engl J Med 2021; 385:372-373. July 22 PMID: 34289282 https://www.nejm.org/doi/full/10.1056/NEJMe2109010
  9. Tumolo J Mixing Pimavanserin With Soft Food Earns Favorable Ratings for Swallowability, Taste. Annals of Long-Term Care. July 22, 2021 - Forman M, Kouassi A, Brandt T. Palatability and Swallowability of Pimavanserin When Mixed with Selected Food Vehicles: An Exploratory Open-Label Crossover Study. Geriatrics (Basel). 2021;6(2):61. Published 2021 Jun 15. PMID: 34203662 PMCID: PMC8293179 Free PMC article
  10. George J Parkinson's Drug Tied to Increased Hospitalizations, Death. Mortality risk persisted in people taking pimavanserin. MedPage Today August 17, 2021 https://www.medpagetoday.com/neurology/parkinsonsdisease/94081 - Hwang YJ, Alexander GC, An H et al Risk of hospitalization and death associated with pimavanserin use in older adults with Parkinson disease. Neurology 2021. August 13 PMID: 34389652 https://n.neurology.org/content/early/2021/08/13/WNL.0000000000012601.abstract - Ali F Pimavanserin: A friend or foe in Parkinson disease psychosis. Neurology 2021. August 13 PMID: 34389650 https://n.neurology.org/content/early/2021/08/13/WNL.0000000000012656
  11. Monaco K FDA Advisers Reject Nuplazid for Alzheimer's Disease Psychosis. Weak trial data not enough to persuade panel to recommend approval. MedPage Today June 17, 2022 https://www.medpagetoday.com/psychiatry/alzheimersdisease/99330
  12. Abler V, Brain C, Ballard C, Berrio A, Coate B, Espay AJ. Motor- and cognition-related safety of pimavanserin in patients with Parkinson's disease psychosis. Front Neurol. 2022. October 5 PMID: 36277907 PMCID: PMC9580496 Free PMC article