Cognitive behavioural therapy for the treatment of schizophrenia spectrum disorders: an umbrella review of meta-analyses of randomised controlled trials.

Background: Cognitive behavioural therapy (CBT) forms the standard psychotherapy for schizophrenia spectrum disorders (SSD). We aimed to summarize and evaluate the evidence on the effectiveness of CBT for SSD. Methods: In this umbrella review, we searched PubMed, Embase, Cochrane Database, and PsychInfo, for meta-analyses of randomised controlled trials (RCTs) of CBT in SSD published between database inception up to Aug 18, 2023. Inclusion criteria were RCTs investigating individually provided CBT in a population of patients with SSD, compared to either standard care, treatment as usually, or any other psychosocial therapies. No restrictions concerning follow-up or language were applied. We used the "assessment of multiple systematic reviews" (AMSTAR-2) appraisal checklist for the evaluation of methodological quality of meta-analysis. We extracted summary metrics from eligible studies in duplicate. The strength of evidence was classified by the sample size, p-value, excess significance bias, prediction intervals, significance of largest study, and heterogeneity. The strength of evidence was ranked according to established criteria as: convincing, highly suggestive, suggestive, weak, or not significant. Primary outcomes were general psychopathology, positive and negative symptoms. This study is registered in PROSPERO, CRD42022334671. Findings: We found 26 eligible meta-analyses, of which 16 meta-analyses provided sufficient data. Using the AMSTAR-2, we found limitations in details concerning the selection of study design, quality of the search and reporting of funding in included meta-analyses. A minority of 42.9% of the comparisons showed a significant result in favor of CBT; 57.1% were non-significant with no convincing or highly suggestive evidence. Suggestive evidence was found in favor of CBT for general psychopathology (6.2%, N = 34 RCTs, effect size (ES) = -0.33 (-0.47; -0.19), I2 = 67.93), delusions (16.7%, N = 27, ES = 0.36 (0.22; 0.51), I2 = 50.47), and hallucinations (33.3%, N = 28, ES = 0.32 (0.19; 0.46), I2 = 45.14) at the end of treatment (EoT). Weak (N = 34 RCTs, ES = -0.13 (-0.24; -0.02), I2 = 51.28), or non-significant evidence (N = 28 RCTs, ES = 0.12 (-0.03; 0.27) I2 = 64.63) was found for negative symptoms at EoT. At longer follow-up, evidence became weak or non-significant. Interpretation: Findings suggest that the effectiveness of CBT on general and positive symptoms in SSD at EoT was small to medium, while we found inconsistent evidence for a sustainable effect. CBT has no convincing impact on other relevant outcomes. Guidelines may use these results to specify their recommendations. Funding: None.

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

The bumpy road to achieve reliability of clinical profile characteristics in psychosis and related disorders.

OBJECTIVES: Profile characteristics are factors that are relevant for diagnosis, prognosis or treatment. The present study aims to develop a set of clinically relevant profile characteristics. Moreover, our goal is to determine the inter-rater reliability (IRR) of the selected profile characteristics. METHODS: Potential profile characteristics were determined by literature review. Assessment of IRR was done by comparing scores on profile characteristics determined by two researchers. We conducted three subsequent studies: (1) assessment of pre-training IRR, (2) IRR following implementation of an instruction manual, (3) IRR after optimizing scoring methods. IRR was measured with the Intraclass Correlation Coefficient (ICC). RESULTS: IRR scores of profile characteristic Illegal activities were high across the three studies (ICC ≥ 0.75). Following training procedures in study 2 and 3, reliability estimates remained low to moderate (ICC < 0.75) for the profile characteristics Support of relatives, Aggression recent and lifetime, substance use and insight recent. IRR scores of the other eight profile characteristics varied from low, moderate to high across studies. CONCLUSION: IRR scores of profile characteristics were highly variable, and mostly inadequate in all three studies. Consequently, further research should focus on specification of severity scores of profile characteristics, optimizing scoring methods and re-evaluation of IRR.

Exploration of symptom dimensions and duration of untreated psychosis within a staging model of schizophrenia spectrum disorders.

AIM: Clinical staging of schizophrenia entails a new method that identifies clusters of symptoms and variation in level of remission, with the goal to create a framework for early intervention. Additionally, duration of untreated psychosis (DUP) may influence symptom severity in the first episode of psychosis (FEP) and could necessitate refining of the staging model. However, consistent evidence concerning variation in symptom severity and DUP between stages is missing. Therefore, we evaluated the clinical validity of the staging model by investigating differences in symptom severity across stages in schizophrenia spectrum disorders. Second, we assessed if a prolonged DUP is associated with higher symptom severity in FEP. METHODS: We performed a cross-sectional study of 291 acutely admitted patients with a schizophrenia spectrum disorder. Patients were assigned to clinical stages following the definition of McGorry. Symptom severity was evaluated with the new DSM-5 Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). In FEP, we determined the DUP. RESULTS: Significantly higher severity scores of CRDPSS items hallucinations (H = 14.34, df = 4, P-value = .006), negative symptoms (H = 19.678, df = 4, P-value = .001) and impaired cognition (H = 26.294, df = 4, P-value = <.001) were found in more advanced stages of disease. Moreover, patients with FEP and a DUP longer than 1 year showed significantly more severe negative symptoms (U = 314 000, P = .015) compared to patients with a DUP shorter than 1 year. CONCLUSIONS: The present study found supporting evidence for the clinical validity of the staging model in schizophrenia spectrum disorders. In addition, we found support for refining the stage "first episode" with information concerning the DUP.

An old but still burning problem: Inter-rater reliability in clinical trials with antidepressant medication.

BACKGROUND: Antidepressant trials are criticized due to potential methodological flaws. Root causes of failing methodology can be found in insufficient inter-rater reliability (IRR) and training practices, leading to higher placebo response and reduced study-power. However, it is unknown to what extent reliability estimates or training procedures are currently included in antidepressant reports. Therefore, we aimed to determine the proportion of publications concerning double-blind randomized controlled antidepressant trials that report on IRR coefficients and training procedures. METHODS: We extracted all double-blind randomized clinical trials (RCTs) from the meta-analysis of Cipriani et al. (2018) concerning the period from 2000 until January 2016. Further, we conducted a Medline-search for double-blind RCTs from January 2016 until January 2020 for additional reports. We identified IRR coefficients and training procedures in these publications. RESULTS: In total we identified 179 double-blind RCTs. Only 4.5% reported an IRR coefficient whereas 27.9% reported training procedures. LIMITATIONS: We did not contact individual authors for additional information regarding implementation of training procedures or inter-rater reliability assessment. CONCLUSIONS: There is a substantial lack of reporting IRR coefficients and training procedures in RCTs with antidepressant medication. Considering the large implications of insufficient reliability, we urge researchers to conduct and report training procedures and reliability estimations.

Staging and profiling for schizophrenia spectrum disorders: Inter-rater reliability after a short training course.

OBJECTIVE: Clinical staging and profiling have been proposed as a new approach in order to refine the diagnostic assessment of schizophrenia spectrum disorders. However, only limited evidence is available for the inter-rater reliability of the clinical staging and profiling model. The aim of the present study was therefore to determine the inter-rater reliability of the clinical staging and profiling model for schizophrenia spectrum disorders, and to investigate whether a short course can improve inter-rater reliability. METHODS: Consecutively recruited inpatients with schizophrenia spectrum disorders were included between January 2015 and January 2016 (study 1), and between March 2018 and October 2018 (study 2). By contrast with the assessors in study 1, all the assessors in study 2 were trained in clinical staging and profiling. We used the clinical staging model proposed by McGorry and identified profile characteristics. Inter-rater reliability was measured using the Intraclass Correlation Coefficient (ICC). RESULTS: The ICC score for clinical staging in study 1 was moderate (0.578). It improved considerably in study 2 (0.757). In general, the ICC scores for the profile characteristics in studies 1 and 2 ranged from poor to sufficient (0.123-0.781). CONCLUSION: This study demonstrated that inter-rater reliability in clinical staging was sufficient after training. However, inter-rater reliability for clinical profile characteristics was highly variable. The general implementation of the clinical staging model for schizophrenia spectrum disorders is therefore feasible but clinical profile characteristics should be used with caution.

Exploring construct validity of clinical staging in schizophrenia spectrum disorders in an acute psychiatric ward.

OBJECTIVE: clinical staging and profiling of schizophrenia spectrum disorders has been proposed to describe and define the heterogenous course of disease. We examined the construct validity of clinical staging in schizophrenia spectrum disorders by measuring differences in distribution and severity of relevant clinical profilers and therapeutic improvement (HoNOS) across clinical stages. METHODS: we performed a prospective cross-sectional study with 258 inpatiënts who met DSM-IV criteria for schizophrenia spectrum disorders, recruited in an acute ward of a psychiatric hospital from 1-1-2015 until 31-12-2016. All patients (N=258) were assigned to a clinical stage, according to the criteria described by McGorry and clinical profilers were determined. Therapeutic improvement was assessed by measuring change in differences in HoNOS score during admission. RESULTS: significant higher severity scores of clinical profilers were found in more advanced stages compared to earlier stages. This pattern was apparent in the clinical profilers negative symptoms (F=4.56, P<0.01), number of psychotic episodes last year (F=13.65, P<0.01), compliance (F=2.76, P<0.05), work and daily activities (F=9.85, P<0.001), living situation (F=3.71, P<0.05), support of close relatives (F=9.38, P<0.001) and pre-morbid functioning (F=7.33, P<0.001). Judicial background was less prevalent in earlier stages compared to more advanced disease stages. No differences in therapeutic improvement (HoNOS) were found between clinical stages. CONCLUSION: this study demonstrates that clinical staging in schizophrenia spectrum disorders has an acceptable construct validity between earlier and more chronic stages of disease. Several clinical profilers increase in more advanced stages compared to earlier clinical stages, which supports construct validity.