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Original Investigation | Meta-analysis

Prognosis of Brief Psychotic Episodes A Meta-analysis

Paolo Fusar-Poli, MD, PhD1,2,3; Marco Cappucciati, MD1,3; Ilaria Bonoldi, MD1,3; L. M. Christy Hui, PhD4; Grazia Rutigliano, MD1; Daniel R. Stahl, PhD5; Stefan Borgwardt, MD, PhD6; Pierluigi Politi, MD, PhD3; Aaron L. Mishara, PsyD7; Stephen M. Lawrie, MD8; William T. Carpenter Jr, MD, PhD9,10; Philip K. McGuire, MD, PhD1
[+] Author Affiliations
1Department of Psychosis Studies, King’s College London, Institute of Psychiatry, London, England
2OASIS Service, South London and the Maudsley National Health Service Foundation Trust, London, England
3Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
4Department of Psychiatry, University of Hong Kong, Hong Kong SAR, China
5Department of Biostatistics, King's College London, Institute of Psychiatry, London, England
6Department of Psychiatry, University of Basel Psychiatric Clinics, Basel, Switzerland
7Department of Clinical Psychology, Chicago School of Professional Psychology, Southern California Campus, Los Angeles, California
8Division of Psychiatry, University of Edinburgh, Edinburgh, Scotland
9Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore
10Veterans Affairs Capitol Health Care Network, Mental Illness Research, Education, and Clinical Center, Veterans Integrated Service Network, Baltimore, Maryland
JAMA Psychiatry. 2016;73(3):211-220. doi:10.1001/jamapsychiatry.2015.2313.
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Importance  The prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown.

Objective  To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES > ATPD > BPD > BIPS > BLIPS.

Data Sources  The Web of Knowledge and Scopus databases were searched up to May 18, 2015; the articles identified were reviewed as well as citations of previous publications and results of a manual search of the reference lists of retrieved articles.

Study Selection  We included original articles that reported the risk of psychotic recurrence at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES.

Data Extraction and Synthesis  Independent extraction by multiple observers. Random-effects meta-analysis was performed, and moderators were tested with meta-regression analyses, Bonferroni corrected. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Publication bias was assessed with funnel plots and the Egger test.

Main Outcomes and Measures  Proportion of patients with baseline ATPD, BPD, BLIPS, and BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up.

Results  Eighty-two independent studies comprising up to 11 133 patients were included. There was no prognostic difference in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS at any follow-up (P > .03). In the long-term analysis, risk of psychotic recurrence (reported as mean [95% CI]) was significantly higher in the FES group (0.78 [0.58-0.93] at 24 months and 0.84 [0.70-0.94] at ≥36 months; P < .02 and P < .001, respectively) compared with the other 4 groups (0.39 [0.32-0.47] at 24 months and 0.51 [0.41-0.61] at ≥36 months). There were no publication biases. Sex and exposure to antipsychotic medication modulated the meta-analytical estimates (.002 < P < .03).

Conclusions and Relevance  There are no prognostic differences in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS constructs of brief psychotic episodes. Conversely, there is consistent meta-analytical evidence for better long-term prognosis of brief psychotic episodes compared with remitted first-episode schizophrenia. These findings should influence the diagnostic practice and clinical services in the management of early psychosis.

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Figure 1.
Historical Genealogy of Current Competing Diagnostic Constructs for Brief Psychotic Episodes

Information available in multiple publications.5,6,8,1027 Adapted from Marneros and Pillmann.14 ATPD indicates acute and transient psychotic disorder; BIPS, brief intermittent psychotic symptoms; BLIPS, brief limited intermittent psychotic symptom; BPD, brief psychotic disorder; CAARMS, Comprehensive Assessment of At-risk Mental State; ICD-10, International Statistical Classification of Diseases, 10th Revision; SIPS, Structured Interview for Prodromal Syndromes; TIA, transient ischemic attack.

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Figure 2.
PRISMA Flow Diagram

ATPD indicates acute and transient psychotic disorder; BIPS, brief intermittent psychotic symptoms; BLIPS, brief limited intermittent psychotic symptom; BPD, brief psychotic disorder; and FES, remitted first-episode schizophrenia.

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Figure 3.
Meta-analytical Prognosis of Brief Psychotic Episodes During Follow-up Time

ATPD indicates acute and transient psychotic disorder; BIPS, brief intermittent psychotic symptoms; BLIPS, brief limited intermittent psychotic symptoms; BPD, brief psychotic disorder; and FES, remitted first-episode schizophrenia.

aP < .05 compared with BLIPS, BIPS, ATPD, and BPD.

bP < .001 compared with BLIPS, BIPS, ATPD, and BPD.

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Further meta analyses are required.
Posted on January 18, 2016
Christopher Gale, Paul Glue
Dunedin School of Medicine, University of Otago.
Conflict of Interest: None Declared
We read with interest the recent meta-analysis on brief psychotic episodes by Fusar-Poli and others (1) There were significant differences between each study in the number of participants with attenuated psychotic state (APS), brief limited intermittent psychosis (BLIPS) and genetic risk and decline (GRD) as clearly shown in the supplementary graphs 1a, 1b and 1c. As the authors noted, although the pooled proportion of participants with APS, BLIPS and GRD were 85%, 10% and 5% respectively, the variation between studies was significant.

Although it has been proposed that the criteria for these three groups are well defined (2), the relationship of these three concepts is less certain. GRD is a construct of family history and deterioration of function. There is overlap between APS and BLIPS and it may be these are stages on a continuum with a first episode (3). The conflation of GRD with these remains unclear.

It may be useful to pool and meta-analyze interventions by clinical subtype, particularly as the study authors have performed most of the relevant studies. This is a unique opportunity to potentially may clarify which interventions are useful for GRD, APS and BLIPS.


1. Fusar-Poli P, Cappucciati M, Bonoldi I, et al. Prognosis of brief psychotic episodes: A meta-analysis. JAMA Psychiatry. 2016 Jan 13;1–10.
2. Cornblatt BA, Carrión RE. Deconstructing the psychosis risk syndrome: Moving the field of prevention forward. JAMA Psychiatry. 2015 Dec 30;1–2.
3. McGorry P, Nelson B. Why we need a transdiagnostic staging approach to emerging psychopathology, early diagnosis, and treatment. JAMA Psychiatry. 2016 Jan 13;1–2.


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