08:30 Uhr
Dose-response meta-analysis of antipsychotic-induced weight gain
H. Wu (München, DE)
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Autor:innen:
H. Wu (München, DE)
S. Siafis (DE)
T. Hamza (CH)
J. Schneider-Thoma (DE)
J. Davis (US)
G. Salanti (CH)
S. Leucht (DE)
Background: Antipsychotic-induced weight gain is a serious problem and is associated with metabolic disturbances, which may cause excess mortality of people with schizophrenia. The relationship between weight gain and antipsychotic doses is still unclear. We conducted a dose-response meta-analysis to look into this question.
Methods: We searched in multiple electronic databases (last update search June 2021) for fixed-dose randomized controlled trials investigating 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. Random-effects dose-response meta-analyses were conducted using restricted cubic splines to model the dose-response relationship. We used mean weight gain in kilogram as the primary outcome and the number of patients with clinically important weight gain as the secondary outcome.
Results: 97 studies with 333 dose arms (36 326 participants) were included in our meta-analyses. Study duration ranged from 4 to 26 weeks, with median duration of 6 weeks. In patients with acute exacerbation of schizophrenia, the following antipsychotics produced mild weight gain (mean difference at any dose≤1 kg) in comparison to placebo: amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone, while more significant weight gain was observed for the rest. For most drugs, dose-response curves showed an initial dose-related increase in weight followed by a plateau at higher doses, while for others curves were still increasing at higher doses and some even had bell-shaped curves, meaning less weight gain to be associated with higher doses.
Interpretation: Second generation antipsychotics do not only differ in their risk of weight gain, but also in their dose-response curves. This information could facilitate better dosing decisions in clinical practice
08:42 Uhr
The clinical relevance of PANSS-derived criteria of relapse in schizophrenia trials: an evaluation using equipercentile linking and diagnostic test accuracy meta-analysis
S. Siafis (München, DE)
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Autor:innen:
S. Siafis (München, DE)
L. Brandt (DE)
R. McCutcheon (GB)
S. Gutwinski (DE)
J. Davis (US)
O. Howes (GB)
C. Correll (DE)
S. Leucht (DE)
Introduction: There is yet no consensus on the criteria of relapse in schizophrenia trials, and scale-derived the are often used. Therefore, we explored the clinical relevance of criteria of relapse based on the Positive and Negative Syndrome Scale (PANSS).
Methods: We used individual-participant data from randomized controlled trials (RCTs) within the Yale University Open Data Access (YODA), which investigated antipsychotic drugs in stable patients with schizophrenia-like disorder. First, we conducted equipercentile linking between change scores in PANSS total, clinical global impression severity (CGI-S) and Personal Social Performance (PSP). Second, we conducted random-effects diagnostic test accuracy (DTA) meta-analysis in order to evaluate the performance of a series of operationalized criteria based on PANSS against a clinically important worsening in global severity of illness in CGI-S (at least 1 point increase and a score of 4) and rehospitalizations.
Results: Data from seven RCTs (2352 participants) were analyzed. We found that an increase of about 10 points in PANSS total corresponded to an increase of about 1 point in CGI-S and a decline of about 10 points in PSP. In addition, an increase of at least 10 points in PANSS total had a good test accuracy to identify participants with a clinically important worsening in global severity of illness and a good sensitivity against to identify participants readmitted to the hospital. The performance of item-based and multifactorial criteria was also assessed.
Discussion: Our analysis could facilitate the selection of proper definitions of relapse in clinical trials of schizophrenia.
08:54 Uhr
Real-world effectiveness of aripiprazole once-monthly: pooled analysis of two non-interventional studies
D. Schöttle (Hamburg, DE)
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Autor:in:
D. Schöttle (Hamburg, DE)
Background: Non-interventional naturalistic studies are an important complement to randomized controlled trials. Aripiprazole once-monthly (AOM) is an atypical antipsychotic in a long-acting injectable formulation.
Methods: A pooled analysis of 2 non-interventional studies was undertaken to validate previous results on AOM effectiveness and safety in a larger population and improve statistical power for pre-planned subgroup analyses. We analyzed data from 409 patients with schizophrenia who were treated with AOM and were enrolled in non-interventional studies in Germany (vfa non-interventional studies registry 15960N) and Canada (NCT02131415). Data collected at baseline, 3 months and 6 months were analyzed. Among the endpoints were psychopathology (Brief Psychiatric Rating Scale, BPRS) and disease severity (Clinical Global Impression, CGI).
Results: Mean patient age was 38.9 (SD 14.8) years, and 59.9% were male. BPRS decreased from 48.1 (SD 15.6) at baseline to 36.5 (SD 13.7) at month 6 (p < 0.001). CGI decreased from 4.47 (SD 0.90) at baseline to 3.64 (SD 1.16) at month 6 (p < 0.001). 54.4% were responders (at least 20% reduction) on the BPRS, and 56.4% had a CGI-S-score that was at least 1 level better than baseline. 43.4% were considered responders on both the BPRS and CGI scales. 45.2% were considered in remission. Adverse events were rare and corresponded to the previously known safety profile of AOM.
Conclusions: Treatment with AOM for patients with schizophrenia appeared effective and safe under real-life conditions.
09:06 Uhr
Exploring the clinical relevance of exercise-effects on brain volume and connectivity in patients with schizophrenia
L. Röll (München, DE)
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Autor:in:
L. Röll (München, DE)
Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. Patients diagnosed with schizophrenia in accordance to the DSM IV were included in this resting-state fMRI analysis. The functional connectome was examined using two global approaches: We computed functional connectivity within and between core intrinsic connectivity networks and assessed functional connectivity between different regions of interest. Multilevel Bayesian partial correlations between aerobic fitness and the functional connectome as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. The current work provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia.