Parkinson's Disease Psychosis and the Marketing of Pimavanserin

Abstract

In 2016, Nuplazid (pimavanserin) became the first FDA-approved treatment for Parkinson's Disease Psychosis (PDP). We explored the possibility that PDP was a term created to market Nuplazid. We examined trends in perceptions of psychosis in Parkinson's disease from the 1990s to 2020 through MEDLINE search term frequency, neurology textbooks, guidance from professional societies, Acadia annual reports, sponsored websites, and a sponsored meeting held by the National Institutes of Health (NIH). We analyzed continuing medical education (CME) activities on PDP and analyzed the connection between payments by the manufacturer of pimavanserin and prescriptions. Our analysis of nine sponsored CME activities reveals misleading themes, including: PDP is common, progressive, and not always drug-induced; there is no such thing as a benign hallucination, and psychotic symptoms always worsen; PDP increases mortality; and competing treatments are ineffective or dangerous while pimavanserin is safe and effective for treating PDP. Industry-sponsored CME was used to disseminate inaccurate and misleading marketing messages on psychosis related to Parkinson's disease. Some professional societies and some textbooks also resisted the PDP label. Reframing PDP as a unique condition is a typical example of condition branding. The establishment of PDP expanded the use of pimavanserin and is likely to have resulted in many avoidable deaths.

Keywords

condition branding continuing medical education parkinson's disease psychosis pharmaceutical marketing

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References

FDA News Release. FDA approves first drug to treat hallucinations and delusions associated with Parkinson’s disease.https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-hallucinations-and-delusions-associated-parkinsons-disease. Published April 29, 2016.

FDA. 2016. Pimavanserin for the Treatment of Psychosis Associated with Parkinson’s Disease. Presented at the Psychopharmacologic Drugs Advisory Committee Meeting, Silver Spring, MD. Retrieved from https://web.archive.org/web/20210306193306/https://www.fda.gov/media/96954/download.

Fenelon

. Hallucinations in Parkinson’s disease: Prevalence, phenomenology and risk factors. Brain. 2000;123(4):733–745. doi:https://doi.org/10.1093/brain/123.4.733

Simon

Aminoff

Greenberg

. Clinical Neurology. 10th ed. McGraw-Hill Education LLC; 2018, Accessed September 10, 2021. http://accessmedicine.mhmedical.com/book.aspx?bookid=2274.

Parry

. The art of branding a condition. Medical Marketing and Media. 2003;38(5):43.

Angelmar

Kane

. Building strong condition brands. J Med Market. 2007;7(4):341–351. doi:https://doi.org/10.1057/palgrave.jmm.5050101

Meixel

Yanchar

Fugh-Berman

. Hypoactive sexual desire disorder: Inventing a disease to sell low libido. J Med Ethics. 2015;41(10):859–862. doi:https://doi.org/10.1136/medethics-2014-102596

Jung

Fugh-Berman

. Marketing messages in Continuing Medical Education (CME) modules on binge-eating disorder (BED). J Am Board Fam Med. 2020;33(2):240–251. doi:https://doi.org/10.3122/jabfm.2020.02.190129

Fugh-Berman

. Industry-funded medical education is always promotion—an essay by Adriane Fugh-Berman. Br Med J. 2021;373:n1273. Published online June 4, 2021. doi:https://doi.org/10.1136/bmj.n1273

10.

Greenberg

Aminoff

Simon

. Clinical Neurology. 2nd ed. Appleton & Lange; 1993.

11.

Simon

Greenberg

Aminoff

. Clinical Neurology. 7th ed. Lange Medical Books/McGraw-Hill; 2009.

12.

Greenberg

Aminoff

Simon

. Clinical Neurology. 8th ed. McGraw Hill; 2012.

13.

Simon

Aminoff

Greenberg

. Clinical Neurology. 10th ed. McGraw-Hill Education LLC; 2018, Accessed September 10, 2021. http://accessmedicine.mhmedical.com/book.aspx?bookid=2274.

14.

Jankovic

Tolosa

, eds. Parkinson’s Disease and Movement Disorders. 4th ed. Lippincott Williams & Wilkins; 2002.

15.

Jankovic

Tolosa

, eds. Parkinson’s Disease and Movement Disorders. 5th ed. Lippincott Williams & Wilkins; 2007.

16.

Jankovic

Tolosa

, eds. Parkinson’s Disease and Movement Disorders. 6th ed. Wolters Kluwer; 2015.

17.

Miyasaki

Shannon

Voon

, et al. Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): [RETIRED]: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):996–1002. doi:https://doi.org/10.1212/01.wnl.0000215428.46057.3d

18.

Zesiewicz

Sullivan

Arnulf

, et al. Practice Parameter: Treatment of nonmotor symptoms of Parkinson disease [RETIRED]: Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2010;74(11):924–931. doi:https://doi.org/10.1212/WNL.0b013e3181d55f24

19.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2004 Annual Report. Acadia Pharmaceuticals Inc.; 2004. https://ir.acadia.com/static-files/eead40a8-1644-429a-8f66-70fa2bf4da0f.

20.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2006 Annual Report. Acadia Pharmaceuticals Inc.; 2006. https://ir.acadia.com/static-files/375cd3c4-3a5b-45cc-ac10-48b4eef02b22.

21.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2008 Annual Report. Acadia Pharmaceuticals Inc.; 2008. https://ir.acadia.com/static-files/dd2b3ffe-eff0-4f7c-9642-4346e165b0ad.

22.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2009 Annual Report. Acadia Pharmaceuticals Inc.; 2009. https://ir.acadia.com/static-files/19ad25fd-807b-4294-a948-eb24a60363b6.

23.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2012 Annual Report. Acadia Pharmaceuticals Inc.; 2012. https://ir.acadia.com/static-files/2446d001-35dd-4967-8023-46063af14568.

24.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2016 Annual Report. Acadia Pharmaceuticals Inc.; 2016. https://ir.acadia.com/static-files/fd8c3cbf-fe1d-4da9-8324-84092d9be628.

25.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2005 Annual Report. Acadia Pharmaceuticals Inc.; 2005. https://ir.acadia.com/static-files/824e3766-0da6-4c56-907c-af799254424b.

26.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2007 Annual Report. Acadia Pharmaceuticals Inc.; 2007. https://ir.acadia.com/static-files/98c81eba-dc5b-4440-8bfe-b44d67282b87.

27.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2010 Annual Report. Acadia Pharmaceuticals Inc.; 2010. https://ir.acadia.com/static-files/e9f99633-028e-461c-8dc0-7915c47c4e8c

28.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2011 Annual Report. Acadia Pharmaceuticals Inc.; 2011. https://ir.acadia.com/static-files/85ea74f5-cd31-4b3d-b817-63c46b151983.

29.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2013 Annual Report. Acadia Pharmaceuticals Inc.; 2013. https://ir.acadia.com/static-files/398fe743-9f50-4ed9-af4f-23d307c30be4.

30.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2014 Annual Report. Acadia Pharmaceuticals Inc.; 2014. https://ir.acadia.com/static-files/723c5800-1394-44e8-9197-5fea70c4b85c.

31.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2015 Annual Report. Acadia Pharmaceuticals Inc.; 2015. https://ir.acadia.com/static-files/ac5b684f-805f-421b-b8c1-5319ebff43c8.

32.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2017 Annual Report on Form 10-K. Acadia Pharmaceuticals Inc.; 2017. https://ir.acadia.com/static-files/2b67833e-a318-432f-afeb-7f219b2ef1ba.

33.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals Inc. 2018 Annual Report. Acadia Pharmaceuticals Inc.; 2018. https://ir.acadia.com/static-files/edac377e-1774-4f21-aefa-f5cfe9903120.

34.

Acadia Pharmaceuticals Inc. Acadia Pharmaceuticals 2019 Annual Report. Acadia Pharmaceuticals Inc.; 2019. https://ir.acadia.com/static-files/78a5e0e6-d0c9-480c-97cb-0b6e06881140.

35.

Acadia Pharmaceuticals Inc. Parkinson’s-Related Hallucinations & Delusions Treatment. Nuplazid. Accessed February 21, 2023. www.nuplazid.com.

36.

Acadia Pharmaceuticals Inc. NUPLAZID (pimavanserin). NUPLAZID (pimavanserin) | For Healthcare Professionals. Accessed August 25, 2020. www.nuplazidhcp.com.

37.

Acadia Pharmaceuticals Inc. Understanding Parkinson’s - Hallucinations & Delusions. More to Parkinson’s. Accessed August 25, 2020. https://www.moretoparkinsons.com/.

38.

Ravina

Marder

Fernandez

, et al. Diagnostic criteria for psychosis in Parkinson’s disease: Report of an NINDS, NIMH work group. Mov Disord. 2007;22(8):1061–1068. doi:https://doi.org/10.1002/mds.21382

39.

Acadia Pharmaceuticals Inc. 2016. Nuplazid (pimavanserin) Sponsor Background Information for a Meeting Of The Psychopharmacologic Drugs Advisory Committee On 29 March 2016 (pp. 1–173). Retrieved from https://web.archive.org/web/20210930144718/https://www.fda.gov/media/96755/download.

40.

FDA. 2016. FDA Briefing Document Psychopharmacologic Drugs Advisory Committee Meeting (pp. 1–107). Retrieved from: https://web.archive.org/web/20211209233211/https://www.fda.gov/media/96750/download.

41.

FDA. 2016. Summary Meeting Minutes. Psychopharmacologic Drugs Advisory Committee. Retrieved from (https://web.archive.org/web/20210305025819/https://www.fda.gov/media/97752/download.

42.

Acadia Pharmaceuticals Inc. 2016. NUPLAZID (pimavanserin). Presented at the Psychopharmacologic Drugs Advisory Committee Meeting, Silver Spring, MD. Retrieved from https://web.archive.org/web/20211020210626/https://www.fda.gov/media/96963/download.

43.

FDA. 2016. Meeting of the Psychopharmacologic Drugs Advisory Committee (PDAC) (Minutes). Psychopharmacologic Drugs Advisory Committee Meeting. https://web.archive.org/web/20210305222551/https://www.fda.gov/media/97761/download.

44.

FDA. 2016. AGENDA. Presented at the Psychopharmacologic Drugs Advisory Committee Meeting, Silver Spring, MD. Retrieved from https://web.archive.org/web/20210305025817/https://www.fda.gov/media/96921/download.

45.

Medscape. Medscape Education. Accessed August 25, 2020. https://www.medscape.org/.

46.

U.S. Centers for Medicare & Medicaid Services. Medicare Provider Utilization and Payment Data: Part D Prescriber. Accessed August 25, 2020. https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Medicare-Provider-Charge-Data/Part-D-Prescriber.

47.

Lang

Lees

. Management of Parkinson’s disease: An evidence-based review. Mov Disord. 2002;17(S4):i–i. doi:https://doi.org/10.1002/mds.5554

48.

Seppi

Weintraub

Coelho

, et al. The movement disorder society evidence-based medicine review update: Treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(S3):S42–S80. doi:https://doi.org/10.1002/mds.2388

49.

Seppi

Ray Chaudhuri

Coelho

, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34(2):180–198. doi:https://doi.org/10.1002/mds.27602

50.

Manheim

. Personal Communication via Emailed Letter with NINDS FOIA Public Liaison OGIS. Published online January 6, 2021.

51.

Armstrong

Weintraub

Fox

, et al. Three Key Clinical Takeaways in Parkinson’s Disease Psychosis. Presented at: August 16, 2016. https://www.medscape.org/viewarticle/867032.

52.

Hermanowicz

Kremens

Okun

, et al. Expert Perspectives on New Treatment Options for Parkinson’s Disease Psychosis. Presented at: March 25, 2016. https://www.medscape.org/viewarticle/858430.

53.

Cummings

. Assessing Your Practice: Recognizing and Managing Parkinson’s Disease Psychosis. Presented at: April 28, 2015. https://www.medscape.org/viewarticle/843118.

54.

Kellogg

Ballard

Isaacson

, et al. The Parkinson’s Disease Psychosis Journal Club: Long-term Care and New Treatments. Presented at: January 29, 2016. https://www.medscape.org/viewarticle/857114.

55.

Cannone

Pahwa

. Parkinson Disease Psychosis: Implications for General Practice. Presented at: November 14, 2018. https://www.medscape.org/viewarticle/904587.

56.

Cannone

Kremens

Durbin

. Long-Term Care Perspectives on Improving Care of Parkinson Disease Psychosis. Presented at: June 9, 2020. https://www.medscape.org/viewarticle/931850.

57.

Weintraub

Fernandez

Okun

Isaacson

Goetz

. Ask the Expert Series Part 1: Challenging Issues in Parkinson’s Disease Psychosis. Presented at: September 19, 2016. https://www.medscape.org/viewarticle/867045.

58.

Black

Okun

. Simulated Patient Cases in Parkinson’s Disease: Can You Diagnose and Treat These Patients? Presented at: September 24, 2019. https://www.medscape.org/viewarticle/868446.

59.

Fernandez

. Parkinson's Disease Psychosis: Causes, Symptoms, and Treatment Options. Presented at: May 27, 2015. https://www.medscape.org/viewarticle/842622.

60.

Molho

Factor

. Parkinson's disease: The treatment of drug-induced hallucinations and psychosis. Curr Neurol Neurosci Rep. 2001;1(4):320–328. doi:https://doi.org/10.1007/s11910-001-0085-8

61.

Ferreira

Katzenschlager

Bloem

, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol. 2013;20(1):5–15. doi:https://doi.org/10.1111/j.1468-1331.2012.03866.x

62.

Visser

Apostolov

Vlaar

AMM

Twisk

JWR

Weinstein

Berendse

. Visual hallucinations in Parkinson’s disease are associated with thinning of the inner retina. Sci Rep. 2020;10(1):21110. doi:https://doi.org/10.1038/s41598-020-77833-1

63.

Llorca

Pereira

Jardri

, et al. Hallucinations in schizophrenia and Parkinson’s disease: An analysis of sensory modalities involved and the repercussion on patients. Sci Rep. 2016;6(1):38152. doi:https://doi.org/10.1038/srep38152

64.

Fenelon

Soulas

de Langavant

Trinkler

Bachoud-Levi

. Feeling of presence in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2011;82(11):1219–1224. doi:https://doi.org/10.1136/jnnp.2010.234799

65.

Hwang

Alexander

Moore

Mehta

. Risk of hospitalization and death associated with pimavanserin use in older adults with Parkinson disease. Neurology. 2021 Sep 28;97(13):e1266–e1275. doi: https://doi.org/10.1212/WNL.0000000000012601

66.

Mitchell

Trivedi

Gennarelli

, et al. Are financial payments from the pharmaceutical industry associated with physician prescribing?: A systematic review. Ann Intern Med. 2021 Mar;174(3):353–361.

67.

U.S. Centers for Medicare & Medicaid Services. Open Payments. Accessed August 25, 2020. https://openpaymentsdata.cms.gov/.

68.

Boyd

. Acadia Pharmaceuticals: This Is Not a Pharmaceutical Company. The Foundation for Financial Journalism. 2018. https://ffj-online.org/2018/07/09/acadia-pharmaceuticals-this-is-not-a-pharmaceuticals-company/. Published July 9 2018.

69.

Mehta

Moore

Alexander

. Association of pharmaceutical industry payments to physicians with prescription and medicare expenditures for pimavanserin. PS (Wash DC). 2021;72(1):77–80. doi:https://doi.org/10.1176/appi.ps.202000251

70.

Roy

Sharma

. FDA declines to approve expanded use of Acadia's antipsychotic drug. Reuters US. https://www.reuters.com/business/future-of-health/us-fda-declines-approve-expanded-use-acadias-antipsychotic-drug-2022-08-05/. Published August 5, 2022.

71.

Bugarski-Kirola

Bitter

Liu

Abbs

Stankovic

. ENHANCE: Phase 3, randomized, double-blind, placebo-controlled study of adjunctive pimavanserin for schizophrenia in patients with an inadequate response to antipsychotic treatment. Schizophr Bull Open. 2022;3(1):sgac006. https://doi.org/10.1093/schizbullopen/sgac006

72.

Bugarski-Kirola

Arango

Fava

, et al. Pimavanserin for negative symptoms of schizophrenia: Results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe. Lancet Psychiatry. 2022;9(1):46–58. doi:https://doi.org/10.1016/S2215-0366(21)00386-2

73.

Nuplazid [Package Insert]. FDA: Acadia Pharmaceuticals, Inc. 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207318lbl.pdf

74.

Food and Drug Administration’ to ‘Blake Burrell’. April 29, 2016. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/207318Orig1s000ltr.pdf.

75.

Ellis

Hikken

. March 9, 2019. New Parkinson’s psychosis drug target of DOJ investigation. CNN Health. https://www.cnn.com/2019/03/08/health/nuplazid-justice-department-invs/index.html.