Clinical outcomes in brief psychotic episodes: a systematic review and meta-analysis

Abstract

Aims Patients with brief psychotic episodes (BPE) have variable and fluctuating clinical outcomes which challenge psychiatric care. Our meta-analysis aims at providing a comprehensive summary of several clinical outcomes in this patient group. Methods A multistep systematic PRISMA/MOOSE-compliant literature search was performed for articles published from inception until 1st March 2021. Web of Science database was searched, complemented by manual search of original articles reporting relevant outcomes (psychotic recurrence, prospective diagnostic change or stability, remission, quality of life, functional status, mortality and their predictors) for patients diagnosed with acute and transient psychotic disorders (ATPD), brief psychotic disorders (BPD), brief intermittent psychotic symptoms (BIPS) and brief limited intermittent psychotic symptoms (BLIPS). Random-effects methods and Q-statistics were employed, quality assessment with Newcastle-Ottawa Scale, assessment of heterogeneity with I2 index, sensitivity analyses (acute polymorphic psychotic disorders, APPD) and multiple meta-regressions, assessment of publication bias with funnel plot, Egger's test and meta-regression (psychotic recurrence and sample size). Results A total of 91 independent articles (n = 94 samples) encompassed 37 ATPD, 24 BPD, 19 BLIPS and 14 BIPS samples, totalling 15 729 individuals (mean age: 30.89 ± 7.33 years, mean female ratio: 60%, 59% conducted in Europe). Meta-analytical risk of psychotic recurrence for all BPE increased from 15% (95% confidence interval (CI) 12–18) at 6 months, 25% (95% CI 22–30) at 12 months, 30% (95% CI 27–33) at 24 months and 33% (95% CI 30–37) at ⩾36 months follow-up, with no differences between ATPD, BPD, BLIPS and BIPS after 2 years of follow-up. Across all BPE, meta-analytical proportion of prospective diagnostic stability (average follow-up 47 months) was 49% (95% CI 42–56); meta-analytical proportion of diagnostic change (average follow-up 47 months) to schizophrenia spectrum psychoses was 19% (95% CI 16–23), affective spectrum psychoses 5% (95% CI 3–7), other psychotic disorders 7% (95% CI 5–9) and other (non-psychotic) mental disorders 14% (95% CI 11–17). Prospective diagnostic change within APPD without symptoms of schizophrenia was 34% (95% CI 24–46) at a mean follow-up of 51 months: 18% (95% CI 11–30) for schizophrenia spectrum psychoses and 17% (95% CI 10–26) for other (non-psychotic) mental disorders. Meta-analytical proportion of baseline employment was 48% (95% CI 38–58), whereas there were not enough data to explore the other outcomes. Heterogeneity was high; female ratio and study quality were negatively and positively associated with risk of psychotic recurrence, respectively. There were no consistent factor predicting clinical outcomes. Conclusions Short-lived psychotic episodes are associated with a high risk of psychotic recurrences, in particular schizophrenia spectrum disorders. Other clinical outcomes remain relatively underinvestigated. There are no consistent prognostic/predictive factors.

Composite immune marker scores associated with severe mental disorders and illness course

“…On the basis of the inflammatory model of SMDs, a set of generally stable and abundantly expressed immune markers encompassing novel markers and markers with established link to SMDs, representing pathways of potential pathophysiological relevance, including neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration, were chosen. Commonly used illness course characteristics were analyzed, including number of illness episodes ( Häfner, 2019 ; Luciano et al, 2021 ; Peters et al, 2016 ; Provenzani et al, 2021 ), suicide attempts ( Black and Miller, 2015 ; Yates et al, 2019 ), comorbid substance use disorder ( Kendler et al, 2019 ; Messer et al, 2017 ) and for bipolar disorder presence of psychotic features ( Burton et al, 2018 ; Keck et al, 2003 ).…”

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study

“…For example, despite the proportion of males historically being generally similar across APS and BLIPS ( 8 , 23 , 42 , 64 ), due to one study (contributing n = 6 BLIPS; 30% of the total sample) only recruiting males, 90% of our BLIPS sample was male, which is substantially higher compared to previous studies (closer to 50%) ( 10 – 12 , 15 ). While greater proportion of males is associated with greater psychosis risk in BLIPS samples ( 65 ), this is also the case in CHR-P more broadly ( 66 ). Enrichment of psychosis risk through other sociodemographic factors outside of CHR-P subgroup (e.g., migrant status, childhood trauma, urbanicity, parental severe mental illness, etc) ( 67 ) could have reduced the likelihood of finding evidence of neurobiological between-group differences and may reduce generalisability more broadly.…”

“…Due to this and the weak-to-moderate evidence for the null hypothesis and fluctuations in neurobiology over the timecourse of the CHR-P state, future research should aim to investigate larger samples of BLIPS and APS with multiple imaging modalities acquired at multiple time points, which can be achieved through collaboration and harmonization of data through large scale international consortia, e.g., HARMONY incorporating NAPLS ( 70 ), PRONIA ( 71 ), PSYSCAN ( 72 ), and ENIGMA ( 73 ). Similarly, recruitment of BLIPS could be improved through expanding CHR-P detection efforts to other brief psychotic conditions (e.g., acute and transient psychotic disorders and brief psychotic episodes), which all have significant overlap with BLIPS ( 65 , 74 – 77 ). More consistent changes in cerebral perfusion in psychosis have been seen in studies measuring cerebral blood volume (CBV) compared to rCBF; ( 78 ) this may be a promising avenue to explore in future research.…”

Acute and transient psychotic disorders: A review of Indian research

“…This percentage reported in Indian studies is comparable to data from other parts of the globe. [ 259 ] Similarly, when we compare the stability of the diagnosis of ATPD with diagnostic stability for schizophrenia and bipolar disorder,[ 260 261 ] it can be said that it is comparable. Accordingly, it can be said that based on the diagnostic stability, ATPD emerges as a separate diagnosis.…”

“…In terms of recurrence rates, studies from India have suggested that in the short term, the recurrence rates are 10%[ 79 ]–11.7%,[ 93 ] and in long-term follow-up, the recurrence rate varies from 35%[ 234 ] to 46.6%. [ 233 ] Accordingly, it can be said that these data from India[ 33 49 60 62 69 78 79 81 85 90 92 93 94 95 97 100 101 104 233 234 235 236 ] and from other parts of the globe[ 259 ] have led to the inclusion of recurrent ATPD in ICD-11.…”