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Dr Correll and Colleagues Reply

To the Editor: We thank Dr Stip for his 2 letters1,2 that were stimulated by our recent report on the characteristics, extant data, and implications pertaining to long-acting injectable antipsychotics (LAIs) in the management of patients with schizophrenia.3 Drawing on the Canadian Quebec universal health care program that covers physician services and hospitalizations for the entire Quebec population, Dr Stip adds interesting information to the discussion about the potential value of LAIs that is relevant to 2 questions: (1) Which physicians may require additional education about LAI use, as they differentially prescribe LAIs less often? and (2) Is the cost barrier of LAI medications possibly offset by potential health care cost savings associated with LAIs?

Analyzing data from January 2008–March 2012 including 1,996 patients with schizophrenia treated with LAIs under real-world conditions, Dr Stip first investigated characteristics of LAI prescribers.1 Consistent with prior data, such as from New York State,4 the degree of LAI prescribing was heterogeneous across the province of Quebec. Moreover, LAI prescribing was less common among physicians who graduated earlier, practiced outside of urban centers, and did not work in both inpatient and outpatient settings.1

This type of analysis can be useful to better understand practice patterns and help focus quality improvement efforts. However, prior studies, such as one from Germany,5 reported results contrary to Dr Stip’s analysis. Heres et al found that older psychiatrists, who may be more familiar with LAI use predating the widespread use of oral second-generation antipsychotics, were more likely to prescribe LAIs.5 Regarding the results provided by Dr Stip, it remains unclear whether prescriber age serves as a proxy for clinical characteristics of caseload. Assuming an average age of 25 years at medical school graduation, these cohorts would have been 45–55 years and 65–75 years of age during the study midpoint of 2010. Thus, the lower LAI prescribing in the older prescriber cohort could be due to a smaller caseload or treating fewer more severely ill patients with schizophrenia. The finding that prescribers working in both inpatient and outpatient settings prescribe more LAIs may point to the fact that prescribers who follow patients across treatment settings are more aware of the frequency and consequences of antipsychotic nonadherence and therefore utilize more LAIs to better bridge the potentially problematic gap between inpatient and outpatient care.

Second, health care costs in the year following LAI initiation were associated with significant health care cost savings compared to the prior year. The cost savings to the province of Quebec was related to lower inpatient care utilization.2 Although health care costs were higher in the year before initiation of LAIs in younger compared to older patients, cost savings were apparent across all 5 age groups spanning < 20 to ≥ 60 years of age2; this underscores our tenet that LAIs should be offered to patients at all illness stages.

Various study designs have investigated the relative effectiveness of oral antipsychotics and LAIs, including mirror-image designs such as that reported by Dr Stip, cohort studies, and randomized controlled trials (RCTs). Each design has pros and cons.6 Nevertheless, database studies7 and recent RCTs8,9 indicate that LAIs have an advantage regarding treatment continuation and relapse/hospitalization over oral antipsychotics in patients early in the course of schizophrenia. These data should be taken into consideration when revising treatment guidelines for schizophrenia, as patients at all stages of the illness could potentially benefit from being offered LAIs. Furthermore, LAIs may also have a role in patients who currently appear treatment adherent, as the risk for nonadherence is high.10

References

1. Stip E. Physician characteristics associated with prescription of long-acting injectable antipsychotics. J Clin Psychiatry. 2017;78(8):e1060.

2. Stip E. Cost reductions associated with long-acting injectable antipsychotics according to patient age. J Clin Psychiatry. 2017;78(8):e1061.

3. Correll CU, Citrome L, Haddad PM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. PubMed doi:10.4088/JCP.15032su1

4. Citrome L, Levine J, Allingham B. Utilization of depot neuroleptic medication in psychiatric inpatients. Psychopharmacol Bull. 1996;32(3):321–326. PubMed

5. Heres S, Hamann J, Kissling W, et al. Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry. 2006;67(12):1948–1953. PubMed doi:10.4088/JCP.v67n1216

6. Haddad PM, Kishimoto T, Correll CU, et al. Ambiguous findings concerning potential advantages of depot antipsychotics: in search of clinical relevance. Curr Opin Psychiatry. 2015;28(3):216–221. PubMed doi:10.1097/YCO.0000000000000160

7. Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168(6):603–609. PubMed doi:10.1176/appi.ajp.2011.10081224

8. Schreiner A, Aadamsoo K, Altamura AC, et al. Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia. Schizophr Res. 2015;169(1–3):393–399. PubMed doi:10.1016/j.schres.2015.08.015

9. Subotnik KL, Casaus LR, Ventura J, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015;72(8):822–829. PubMed doi:10.1001/jamapsychiatry.2015.0270

10. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12(3):216–226. PubMed doi:10.1002/wps.20060

Christoph U. Correll, MDa

ccorrell@northwell.edu

Leslie Citrome, MD, MPHb

Peter M. Haddad, MDc

John Lauriello, MDd

Mark Olfson, MD, MPHe

John M. Kane, MDa

aDepartment of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, New York, and Department of Psychiatry, The Zucker Hillside Hospital, New Hyde Park, New York

bDepartment of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York

cUniversity of Manchester, Salford, United Kingdom

dDepartment of Psychiatry, University of Missouri, Columbia, Missouri

eDepartment of Psychiatry, Columbia University, New York, New York

Potential conflicts of interest: Dr Correll has affiliations with Acadia, Actavis, Alkermes, Eli Lilly, FORUM, Genentech, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/Johnson & Johnson (J&J), Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus, Takeda, and Teva (consulting); and FORUM, Janssen/J&J, Lundbeck, Otsuka, Pfizer, ProPhase, Sunovion, and Takeda (non-CME/CE services). Dr Citrome has affiliations with Alexza, Alkermes, Allergan, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FORUM, Genentech, Janssen, Jazz, Lundbeck, Merck, Medivation, Mylan, Novartis, Noven, Otsuka, Pfizer, Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva, Valeant, and Vanda (consulting); Alkermes, Allergan, AstraZeneca, Janssen, Jazz, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Shire, Sunovion, Takeda, and Teva (speakers’ bureau); and Bristol-Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer (ownership). Dr Haddad has affiliations with Allergan, Galen, Janssen, Lundbeck, Newbridge, Otsuka, Quantum, Sunovion, and Teva (consulting); and Janssen, Lilly, Lundbeck, Otsuka, Servier, Sunovion, and Takeda (lecturing). Dr Lauriello has affiliations with Reckitt Benckiser (consulting); and Alkermes and Janssen (research). Dr Olfson has an affiliation with Sunovion (salary). Dr Kane has affiliations with Alkermes, Eli Lilly, FORUM, Forest, Genentech, Lundbeck, Intra-Cellular Therapies, Janssen/J&J, Otsuka, Reviva, Roche, Sunovion, and Teva (consulting); Janssen, Genentech, Lundbeck, and Otsuka (honoraria); and MedAvante and Vanguard Research Group (ownership).

Funding/support: The JCP supplement article by Correll et al [2016;77(suppl 3):1–24] discussed in this letter was supported by educational grants from Janssen Pharmaceuticals, Inc., administered by Janssen Scientific Affairs, LLC, and Alkermes.

J Clin Psychiatry 2017;78(8):e1062

https://doi.org/10.4088/JCP.16lr11402a

© Copyright 2017 Physicians Postgraduate Press, Inc.