Factors Associated with the Initiation of Long-Acting Injectable Paliperidone Palmitate Versus Aripiprazole Among Medicaid Patients with Schizophrenia: An Observational Study

  • Qian CaiEmail author
  • Charmi Patel
  • Edward Kim
  • Nancy Connolly
  • Ozgur Tunceli
  • Antoine C. El Khoury
Original Research



Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia.


Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12 months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP.


Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p < 0.01). Patients with obesity (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.71, 0.98), post-traumatic stress disorder (OR 0.76; 95% CI 0.63, 0.92), or prior oral antipsychotic use (OR 0.66; 95% CI 0.55, 0.79) were less likely to initiate LAI-PP; whereas, patients with nonorganic psychoses (OR 1.35; 95% CI 1.18, 1.55) or prior use of other injectable antipsychotics (OR 1.26; 95% CI 1.09, 1.47) were more likely to initiate LAI-PP versus LAI-AP. Patients with at least two all-cause hospitalizations were 1.37 times more likely to initiate LAI-PP vs LAI-AP (OR 1.37; 95% CI 1.18, 1.60).


Factors associated with initiating LAI-PP and LAI-AP differed. Notably, patients who initiated LAI-PP had greater prior use of medical services than LAI-AP patients. Understanding prescribing practices may help optimize treatment strategies and improve disease management.


Janssen Scientific Affairs, LLC.


Aripiprazole Claims database Long-acting injectables Medicaid Mental health Paliperidone palmitate Real-world evidence Schizophrenia 




This study was sponsored by Janssen Scientific Affairs, LLC. The study sponsor also funded the journal’s article processing charges. All authors had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Medical Writing and Editorial Assistance

Editorial assistance in the preparation of this article was provided by Prabhakar Pandey of SIRO Clinpharm Pvt. Ltd. Support for this assistance was funded by Janssen Scientific Affairs, LLC.


All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published.

Authorship Contributions

Conception and design: QC, ACE, CP, OT, EK. Collection and assembly of data: QC. Data analysis and interpretation: QC, OT. Manuscript writing: All authors. Final approval of manuscript: All authors.


Qian Cai is an employee of and holds stock in Johnson & Johnson. Charmi Patel is an employee of and holds stock in Johnson & Johnson. Edward Kim is an employee of and holds stock in Johnson & Johnson. Nancy Connolly is an employee of and holds stock in Johnson & Johnson. Ozgur Tunceli is an employee of and holds stock in Johnson & Johnson. Antoine C El Khoury is an employee of and holds stock in Johnson & Johnson.

Compliance with Ethics Guidelines

All data were de-identified and fully complied with the US Health Insurance Portability and Accountability Act; therefore, this study was exempted from institutional review board review [27].

Data Availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.


  1. 1.
    Desai PR, Lawson KA, Barner JC, Rascati KL. Estimating the direct and indirect costs for community-dwelling patients with schizophrenia. J Pharm Health Serv Res. 2013;4(4):187–94. Scholar
  2. 2.
    Wu EQ, Shi L, Birnbaum H, Hudson T, Kessler R. Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach. Psychol Med. 2006;36(11):1535–40. Scholar
  3. 3.
    National Institutes of Mental Health. Schizophrenia. 2018 [updated May 2018]. Accessed Nov 2018.
  4. 4.
    Fitch K, Iwasaki K, Villa KF. Resource utilization and cost in a commercially insured population with schizophrenia. Am Health Drug Benef. 2014;7(1):18–26.Google Scholar
  5. 5.
    Cloutier M, Aigbogun MS, Guerin A, et al. The economic burden of schizophrenia in the United States in 2013. J Clin Psychiatry. 2016;77(6):764–71. Scholar
  6. 6.
    MacEwan JP, Forma FM, Shafrin J, Hatch A, Lakdawalla DN, Lindenmayer JP. Patterns of adherence to oral atypical antipsychotics among patients diagnosed with schizophrenia. J Manag Care Spec Pharm. 2016;22(11):1349–61.
  7. 7.
    Jakovljevic M. Long-acting injectable (depot) antipsychotics and changing treatment philosophy: possible contribution to integrative care and personal recovery of schizophrenia. Psychiatr Danub. 2014;26(4):304–7.Google Scholar
  8. 8.
    Kishimoto T, Hagi K, Nitta M, et al. Effectiveness of long-acting injectable vs oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies. Schizophr Bull. 2018;44(3):603–19. Scholar
  9. 9.
    Marcus SC, Zummo J, Pettit AR, Stoddard J, Doshi JA. Antipsychotic adherence and rehospitalization in schizophrenia patients receiving oral versus long-acting injectable antipsychotics following hospital discharge. J Manag Care Spec Pharm. 2015;21(9):754–68.
  10. 10.
    Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophrenia–a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res. 2011;127(1–3):83–92. Scholar
  11. 11.
    Baser O, Xie L, Pesa J, Durkin M. Healthcare utilization and costs of Veterans Health Administration patients with schizophrenia treated with paliperidone palmitate long-acting injection or oral atypical antipsychotics. J Med Econ. 2015;18(5):357–65.
  12. 12.
    Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013;74(10):957–65. Scholar
  13. 13.
    Lafeuille MH, Grittner AM, Fortier J, et al. Comparison of rehospitalization rates and associated costs among patients with schizophrenia receiving paliperidone palmitate or oral antipsychotics. Am J Health Syst Pharm. 2015;72(5):378–89. Scholar
  14. 14.
    Lafeuille MH, Laliberte-Auger F, Lefebvre P, Frois C, Fastenau J, Duh MS. Impact of atypical long-acting injectable versus oral antipsychotics on rehospitalization rates and emergency room visits among relapsed schizophrenia patients: a retrospective database analysis. BMC Psychiatry. 2013;13:221.
  15. 15.
    Offord S, Wong B, Mirski D, Baker RA, Lin J. Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral. J Med Econ. 2013;16(2):231–9.
  16. 16.
    Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168(6):603–9. Scholar
  17. 17.
    Cuomo I, Kotzalidis GD, de Persis S, et al. Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life. Neuropsychiatr Dis Treat. 2018;14:1645–56.
  18. 18.
    US Food and Drug Administration. INVEGA SUSTENNA: Highlights of prescribing information. 2017. Accessed Nov 2018.
  19. 19.
    US Food and Drug Administration. ABILIFY MAINTENA: Highlights of prescribing information. 2016. Accessed Nov 2018.
  20. 20.
    US Food and Drug Administration. ARISTADA: Highlights of prescribing information. 2015. Accessed Nov 2018.
  21. 21.
    Pilon D, Tandon N, Lafeuille MH, et al. Treatment patterns, health care resource utilization, and spending in Medicaid beneficiaries initiating second-generation long-acting injectable agents versus oral atypical antipsychotics. Clin Ther. 2017;39(10):1972–85 e2.
  22. 22.
    Dencker SJ, Axelsson R. Optimising the use of depot antipsychotics. CNS Drugs. 1996;6(5):367–81.CrossRefGoogle Scholar
  23. 23.
    Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56Google Scholar
  24. 24.
    Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry. 2013;14(1):2–44.
  25. 25.
    Florida best practice psychotherapeutic medication guidelines for adults. 2017–2018. 2018. Accessed 2 Nov 2018.
  26. 26.
    Sajatovic M, Ross R, Legacy SN, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder - expert consensus survey part 2. Neuropsychiatr Dis Treat. 2018;14:1475–92.
  27. 27.
    Department of Health and Human Services National Institutes of Health Office for Protection from Research Risks. Code of Federal Regulations, Title 45, public welfare, part 46, protection of human subjects §46.101 2006. 1991. (revised June 18, 1991; accessed 14 Feb 2019).
  28. 28.
    Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82. Scholar
  29. 29.
    US Bureau of Labor Statistics. CPI Detailed Report. 2018. Accessed Nov 2018.
  30. 30.
    US Food and Drug Administration. INVEGA TRINZA: Highlights of prescribing information 2015. 2018. Accessed Sept 2018.
  31. 31.
    Kishimoto T, Sanghani S, Russ MJ, et al. Indications for and use of long-acting injectable antipsychotics: consideration from an inpatient setting. Int Clin Psychopharmacol. 2017;32(3):161–8. Scholar
  32. 32.
    Rajagopalan K, Hassan M, Boswell K, Sarnes E, Meyer K, Grossman F. Review of outcomes associated with restricted access to atypical antipsychotics. Am J Manag Care. 2016;22(6):e208–e214214.Google Scholar
  33. 33.
    Whitney Z, Boyda HN, Procyshyn RM, et al. Therapeutic drug levels of second generation antipsychotics in youth: a systematic review. J Child Adolesc Psychopharmacol. 2015;25(3):234–45. Scholar
  34. 34.
    Kronick RG, Bella M, Gilmer TP. Faces of Medicaid III: refining the portrait of people with multiple chronic conditions. Center for Health Care Strategies, Inc. 2009. Accessed Sept 2018.
  35. 35.
    Brown JD, Barrett A, Ireys H, Caffery E, Hourihan K. Evidence-based practices for Medicaid beneficiaries with schizophrenia and bipolar disorder. Washington, DC: US Department of Health and Human Services, Office of Disability, Aging and Long-Term Care Policy. 2012. Accessed Sept 2018.
  36. 36.
    Joshi K, Lafeuille MH, Kamstra R, et al. Real-world adherence and economic outcomes associated with paliperidone palmitate versus oral atypical antipsychotics in schizophrenia patients with substance-related disorders using Medicaid benefits. J Comp Eff Res. 2018;7(2):121–33. Scholar
  37. 37.
    Gaviria AM, Franco J, Rico G, et al. Noninterventional, naturalistic, retrospective study to describe prescription patterns of long-acting injectable antipsychotics and the impact of introducing a new atypical antipsychotic in the Spanish province of Tarragona catchment area. Prim Care Companion CNS Disord. 2017.
  38. 38.
    Patel R, Chesney E, Taylor M, Taylor D, McGuire P. Is paliperidone palmitate more effective than other long-acting injectable antipsychotics? Psychol Med. 2018;48(10):1616–23. Scholar
  39. 39.
    Masand PS, Roca M, Turner MS, Kane JM. Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia: a review. Prim Care Companion J Clin Psychiatry. 2009;11(4):147–54. Scholar
  40. 40.
    Brasso C, Bellino S, Bozzatello P, Montemagni C, Rocca P. Role of 3-monthly long-acting injectable paliperidone in the maintenance of schizophrenia. Neuropsychiatr Dis Treat. 2017;13:2767–79.
  41. 41.
    Brown JD, Barrett A, Caffery E, Hourihan K, Ireys HT. State and demographic variation in use of depot antipsychotics by Medicaid beneficiaries with schizophrenia. Psychiatr Serv. 2014;65(1):121–4. Scholar
  42. 42.
    Kreyenbuhl J, Zito JM, Buchanan RW, Soeken KL, Lehman AF. Racial disparity in the pharmacological management of schizophrenia. Schizophr Bull. 2003;29(2):183–93.CrossRefGoogle Scholar
  43. 43.
    Kohen I, Lester PE, Lam S. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole. Neuropsychiatr Dis Treat. 2010;6:47–58.CrossRefGoogle Scholar
  44. 44.
    Kari F, Bryan B, Paul J. The use of claims data in healthcare research. Open Public Health J. 2009;2(1)Google Scholar
  45. 45.
    Walsh EG, Clark WD. Managed care and dually eligible beneficiaries: challenges in coordination. Health Care Financ Rev. 2002;24(1):63–82.Google Scholar
  46. 46.
    Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063–71. Scholar

Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Qian Cai
    • 1
    Email author
  • Charmi Patel
    • 1
  • Edward Kim
    • 1
  • Nancy Connolly
    • 1
  • Ozgur Tunceli
    • 1
  • Antoine C. El Khoury
    • 1
  1. 1.Janssen Scientific Affairs, LLCTitusvilleUSA

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