Mariah W Panoussi, BS, MBS

Thirteen-fold disparities between states in clozapine prescriptions to United States Medicaid patients Interview with:

Mariah W Panoussi, BS, MBS

Mariah W Panoussi

Mariah W Panoussi, BS, MBS
Second-year medical student at Saba University School of Medicine, Saba, Dutch Caribbean
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, PA What is the background for this study?

Response: Clinical guidelines currently state that the atypical antipsychotic clozapine effectively treats patients with treatment-resistant schizophrenia (TRS) 1. TRS occurs in up to one-third of patients with schizophrenia.2,3 However, there is evidence that demonstrates a lack of clozapine utilization by providers.2 This underutilization has been attributed to clozapine’s numerous adverse effects, in particular agranulocytosis.4 Other barriers include close monitoring for agranulocytosis, changes in administration and registry programs, as well as concerns regarding physician’s attitude toward and knowledge about clozapine.4,5 These barriers have thus caused a sizable variation in clozapine usage throughout the US. Using Medicaid data from 2015-2019, we conducted a secondary data analysis to examine the varied usage of clozapine in the US Medicaid programs.6 What are the main findings?

Response: States in the upper Midwest and Northeast regions were found to have the highest average clozapine prescriptions per 10,000 Medicaid enrollees from 2015-2019. The states with lower prescription rates were in the Southeast and Southwest US. South Dakota had the highest clozapine prescribing rate (191.6), while Arkansas was the lowest (14.7). Between these two states, there was a 13.0-fold difference in clozapine prescribing rate. Total clozapine prescription rates remained relatively constant during 2015-2019, except for a considerable drop in 2017.6 What should readers take away from your report?

Response:  Due to this nationwide variation in clozapine, there must be a reevaluation on how to improve provider education on the usage and monitoring of patients on clozapine.4,5 There was a significant impact on race affecting the likelihood of prescribing clozapine6. Thus, this disparity must be addressed to improve the health of racial minority patients with TRS.7 Clozapine usage can also increase if there was improved integration of care and effective communication among psychiatrists, primary care physicians, advanced practitioners, and pharmacists.8 What recommendations do you have for future research as a result of this study?

Response: Future research would include a pharmacoeconomic evaluation among different state formulations of clozapine. An in-depth analysis on the cost effectiveness of clozapine compared with long-acting injectable antipsychotics would also enlighten the benefits of clozapine. It would be beneficial if a point of care device was developed for patient use at home for self-monitoring while on clozapine. The analysis of US Medicaid prescription utilization could be expanded to other second-generation antipsychotic medications. Lastly, development of physician education and integrated care programs would improve prescriber reluctance to prescribe clozapine. Is there anything else you would like to add? Any disclosures?

Response:  Brian J. Piper was (2019-2021) part of an osteoarthritis research team supported by Eli Lilly and Pfizer. The other authors have no disclosures.

Data was obtained from: Drug Utilization 2020 – National Totals.9 This is a freely available national database. We continue to be surprised that this is not used more by other pharmacoepidemiology or pharmaco-economics studies.


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  5. Kelly DL, Freudenreich O, Sayer MA, et al. Addressing barriers to clozapine underutilization: A national effort. Psychiatr Serv 2018; 69: 224–227.
  6. Benito RA, Gatusky MH, Panoussi MW, et al. Thirteen-fold variation between states in clozapine prescriptions to United States Medicaid patients. Schizophr Res 2023; 255:79-81.
  7. Stroup TS, Gerhard T, Crystal S, et al. Geographic and clinical variation in clozapine use in the United States. Psychiatr Serv 2014; 65: 186–192.
  8. van der Zalm YC, Schulte PF, Bogers JPAM, Termorshuizen F, Marcelis M, van Piere MAGB, et al. Delegating clozapine monitoring to advanced nurse practitioners: an exploratory, randomized study to assess the effect on prescription and its safety. Adm Policy Ment Health. 2020 Jul;47(4):632–40.
  9. (accessed April 22, 2023).
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Last Updated on April 25, 2023 by Marie Benz