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Abstract

Objective:

This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses.

Methods:

The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation (“acceptability”). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation).

Results:

Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone).

Conclusions:

LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

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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
Pages: 424 - 436
PubMed: 33596679

History

Received: 28 July 2020
Revision received: 27 November 2020
Accepted: 2 December 2020
Published online: 18 February 2021
Published in print: May 01, 2021

Keywords

  1. Antipsychotics
  2. Depot Formulation
  3. Network Meta-Analysis
  4. Relapse Prevention
  5. Maintenance Treatment

Authors

Details

Giovanni Ostuzzi, M.D., Ph.D. [email protected]
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Federico Bertolini, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Cinzia Del Giovane, Ph.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Federico Tedeschi, Ph.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Chiara Bovo, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Chiara Gastaldon, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Michela Nosé, M.D., Ph.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Filippo Ogheri, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Davide Papola, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Marianna Purgato, Psy.D., Ph.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Giulia Turrini, Psy.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Christoph U. Correll, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).
Corrado Barbui, M.D.
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, and Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy (Ostuzzi, Bertolini, Tedeschi, Gastaldon, Nosé, Ogheri, Papola, Purgato, Turrini, Barbui); Institute of Primary Health Care, University of Bern, Bern, Switzerland (Del Giovane); University Hospital of Verona, Verona, Italy (Bovo); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin (Correll).

Notes

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

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