Pimavanserin: A 2019 Clarification on the FDA Update

See letter by Mohanty et al

Pimavanserin: A 2019 Clarification on the FDA Update

To the Editor: It was with great interest that we read the letter to the editor titled "Pimavanserin for Parkinson Disease Psychosis" by Mohanty et al1 published in The Primary Care Companion for CNS Disorders. This letter discusses Parkinson disease psychosis (PDP) including the clinical features, pathophysiology, and treatments such as quetiapine, clozapine, and the recently introduced antipsychotic, pimavanserin. Although Mohanty and colleagues1 provide a thorough overview of pimavanserin’s mechanism of action and pharmacokinetics, we would like to elaborate on their discussion of pimavanserin’s safety considerations.

The authors state, "As of May 2018, the drug’s safety is currently being evaluated following reports of serious adverse events" and reference an article2 published in The Lancet on May 5, 2018, titled "Pimavanserin Evaluated by the FDA" when discussing the drug’s disadvantages. In September 2018, the US Food and Drug Administration (FDA) had already completed a thorough review of all postmarketing reports of deaths and serious adverse events reported with the use of pimavanserin and posted an online update titled "FDA Analysis Finds No New or Unexpected Safety Risks Associated With Nuplazid (pimavanserin), a Medication to Treat the Hallucinations and Delusions of Parkinson’s Disease Psychosis."3 We believe that the omission of this FDA drug safety update could add to pimavanserin’s prescribing worries and possibly contribute to its underutilization.

We concur with Mohanty et al’s description of pimavanserin’s various side effects such as QT interval prolongation, peripheral edema, nausea, confusion, hallucination, constipation, and gait disturbance and that it is associated with increased risk of death in elderly patients with dementia-related psychosis.1,3,4 Similar to pimavanserin, quetiapine is associated with increased risk of death in elderly patients with dementia-related psychosis and must be used cautiously with drugs that increase QT intervals and in patients with prolonged QT interval.5 Additional side effects include neuroleptic malignant syndrome, suicidal thoughts and behavior, somnolence, orthostatic hypotension, dizziness, stroke, myocarditis, and coronary heart disease.5 On the other hand, clozapine requires weekly complete blood count monitoring for the first 6 months followed by every other week for the next 6 months due to the rare but significant risk of agranulocytosis.6 Black box warnings for clozapine include neutropenia, orthostatic hypertension, seizures, myocarditis, and dementia.6

According to a 6-week placebo-controlled trial,3 no events of neuroleptic malignant syndrome, tardive dyskinesia, or serotonin syndrome were reported with pimavanserin (34 mg). Both clozapine and pimavanserin have demonstrated proven efficacy for PDP without impairing motor function.7 Clozapine has a faster onset of action (1 week) compared to pimavanserin (4-6 weeks).7 Although quetiapine is frequently used for PDP, its efficacy has not been demonstrated by double-blind, randomized trials.7 Understandably so, pimavanserin is the only FDA-approved therapy proven to reduce delusions and hallucinations associated with PDP in elderly patients without impacting motor function.3

We would like to thank Mohanty and colleagues1 for their discussion and bringing to light important facts about the role of antipsychotics in Parkinson disease and the pros and cons of antipsychotic use in PDP.

Zeeshan Mansuri, MD, MPHa

[email protected]

Krupa Patel, MDb

Rupak Desai, MBBSc

Muhammad Khalid Zafar, MDa

Shailesh Jain, MD, MPH, ABDAa

Dr Mohanty and colleagues were shown this letter and declined to comment.

aDepartment of Psychiatry, Texas Tech University Health Science Center at Odessa/Permian Basin, Odessa, Texas

bAvalon University School of Medicine, Willemstad, Curaçao, The Netherlands Antilles

cDivision of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia

Potential conflicts of interest: None.

Funding/support: None.

Published online: December 26, 2019.

Prim Care Companion CNS Disord 2020;21(6):19l02495

To cite: Mansuri Z, Patel K, Desai R, et al. Pimavanserin: a 2019 clarification on the FDA update. Prim Care Companion CNS Disord. 2020;21(6):19l02495.

To share: https://doi.org/10.4088/PCC.19l02495

© Copyright 2019 Physicians Postgraduate Press, Inc.

References

1. Mohanty D, Sarai S, Naik S, et al. Pimavanserin for Parkinson disease psychosis. Prim Care Companion CNS Disord. 2019;21(2):18l02355. PubMed CrossRef

2. Webster P. Pimavanserin evaluated by the FDA. Lancet. 2018;391(10132):1762. PubMed CrossRef

3. FDA analysis finds no new or unexpected safety risks associated with Nuplazid (pimavanserin), a medication to treat the hallucinations and delusions of Parkinson’s disease psychosis. US Food & Drug Administration website. https://www.fda.gov/drugs/drug-safety-and-availability/fda-analysis-finds-no-new-or-unexpected-safety-risks-associated-nuplazid-pimavanserin-medication. September 20, 2018. Accessed December 2, 2019.

4. Nuplazid (pimavanserin) 34 mg capsules: the safety story. Nuplazidhcp.com website. https://www.nuplazidhcp.com/safety-tolerability. 2019. Accessed May 3, 2019.

5. Maan JS, Saadabadi A. Quetiapine. [updated 2019 May 5]. StatPearls website. https://www.ncbi.nlm.nih.gov/books/NBK459145/. Accessed December 2, 2019.

6. Haidary HA, Padhy RK. Clozapine. [updated 2018 Dec 21]. StatPearls website. https://www.ncbi.nlm.nih.gov/books/NBK535399/. Accessed December 2, 2019.

7. Friedman JH. Pharmacological interventions for psychosis in Parkinson’s disease patients. Expert Opin Pharmacother. 2018;19(5):499-505. PubMed CrossRef