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Published Online: 14 July 2021

Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs

Mark Weiser, M.D. [email protected], John M. Davis, M.D., Clayton H. Brown, Ph.D., Eric P. Slade, Ph.D., Li Juan Fang, M.S., Deborah R. Medoff, Ph.D., Robert W. Buchanan, M.D., Linda Levi, B.Sc., Michael Davidson, M.D, and Julie Kreyenbuhl, Pharm.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 178, Number 10
https://doi.org/10.1176/appi.ajp.2020.20111657
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Abstract

Objective:

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system.

Methods:

This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group.

Results:

In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine.

Conclusions:

In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 178 • Number 10 • October 01, 2021
Pages: 932 - 940
PubMed: 34256606

History

Received: 26 November 2020
Revision received: 5 February 2021
Accepted: 8 March 2021
Published online: 14 July 2021
Published in print: October 01, 2021

Keywords

  1. Antipsychotics
  2. Long-Acting Injectable
  3. Treatment Discontinuation
  4. Schizophrenia

Authors

Affiliations

Mark Weiser, M.D. [email protected]
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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John M. Davis, M.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Clayton H. Brown, Ph.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Eric P. Slade, Ph.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Li Juan Fang, M.S.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Deborah R. Medoff, Ph.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Robert W. Buchanan, M.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Linda Levi, B.Sc.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Michael Davidson, M.D
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Julie Kreyenbuhl, Pharm.D., Ph.D.
Stanley Medical Research Institute, Kensington, Md. (Weiser); Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Weiser, Levi); Department of Psychiatry, Tel Aviv University, Ramat Aviv, Israel (Weiser); Department of Psychiatry, University of Illinois, Chicago (Davis); VA Capitol Healthcare Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC), Baltimore (Brown, Medoff, Kreyenbuhl); Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Brown; Medoff, Kreyenbuhl); Johns Hopkins School of Nursing, Baltimore (Slade); Department of Psychiatry, Division of Psychiatric Services Research, University of Maryland School of Medicine, Baltimore (Fang); Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore (Buchanan); and University of Nicosia Medical School, Nicosia, Cyprus (Davison)
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Notes

Send correspondence to Dr. Weiser ([email protected]).

Competing Interests

Dr. Weiser has received advisory board, speaker’s, and/or consultant fees from and owns stock with Acadia, Dexcel, Janssen, Lundbeck, Minerva, Pfizer, Roche, and Teva. Dr. Buchanan has served on advisory boards for Acadia, Avanir, GW Pharma, Merck, Minerva, and Roche; he has served as a consultant to Boehringer Ingelheim and Takeda; and he has served on a data safety monitoring board for Roche. Dr. Davidson is an employee of and owns stock options with Minerva Neurosciences. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by the Stanley Medical Research Institute. The content in this article is also the result of work supported with resources provided by the VA VISN 5 MIRECC and the use of facilities at the VA Maryland Health Care System, Baltimore. The contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

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