Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis.
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ABSTRACT:
SUBMITTER: Huhn M
PROVIDER: S-EPMC6891890 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cortical thickness reductions are evident in schizophrenia (SZ). Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in SZ patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex. Structural magnetic resonance imaging was obtained from 127 medication-naive first-episode SZ patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n = 75) or nonresponders (NRs, n = 52) at follow-up. Using surface-based morphometry and structural covariance (SC) analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical covariance. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between covariance and cortical thinning was examined by SC analysis among the top-n regions with thickness reduction. Widespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical covariance and higher network integration in responders than in NRs. For the NRs, some of the prefrontal and temporal nodes were not covariant between the top-n regions with cortical thickness reduction. Antipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.
| S-EPMC8781340 | biostudies-literature
Project description:BackgroundWhile clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression.MethodsEfficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.ResultsEighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12).ConclusionsIn this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.
| S-EPMC8112003 | biostudies-literature
Project description:Purpose: Comprehensive and longitudinal brain analysis is of great significance for understanding the pathological changes of antipsychotic drug treatment in patients with schizophrenia. This study aimed to investigate the changes of structure, function, and network properties in patients with first-episode schizophrenia (FES) after antipsychotic therapy and their relationship with clinical symptoms. Materials and Methods: A total of 30 patients diagnosed with FES and 30 healthy subjects matched for sex and age were enrolled in our study. Patients at baseline were labeled as antipsychotic-naive first-episode schizophrenia (AN-FES), and patients after antipsychotic treatment were labeled as antipsychotic treatment first-episode schizophrenia (AT-FES). The severity of illness was measured by using the PANSS and CGI score. Structural and functional MRI data were also performed. Differences in GMV, ALFF, and ReHo between the FES group and healthy control group were tested using a voxel-wise two-sample t-test, and the comparison of AN-FES group and AT-FES group was evaluated by paired-sample t-test. Results: After the 1-year follow-up, the FES patients showed increased GMV in the right cerebellum, right inferior temporal gyrus, left middle frontal gyrus, parahippocampal gyrus, bilateral inferior parietal lobule, and reduced GMV in the left occipital lobe, gyrus rectus, right orbital frontal cortex. The patients also showed increased ALFF in the medial superior frontal gyrus and right precentral gyrus. For network properties, the patients showed reduced characteristic path length and increased global efficiency. The GMV of the right inferior parietal lobule was negatively correlated with the clinical symptoms. Conclusions: Our study showed that the antipsychotic treatment contributed to the structural alteration and functional improvement, and the GMV alteration may be associated with the improvement of clinical symptoms.
| S-EPMC8668948 | biostudies-literature
Project description:This study examined the miRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia. This study examined the lncRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia. This study examined the mRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia.
2023-08-30 | GSE228881 | GEO
Project description:Background: The maintenance of antipsychotic treatment is an efficient way to prevent the relapse of schizophrenia (SCZ). Previous studies have identified beneficial effects of antipsychotics on brain structural and functional abnormalities during mostly the acute phase in SCZ, but seldom is known about the effects of long-term antipsychotics on the brain. The present study focused on the long-term antipsychotic effect on the default mode network (DMN) dysfunction in SCZ. Methods: A longitudinal study of the functional connectivity (FC) of 11 DMN subdivisions was conducted in 86 drug-naive first-episode patients with SCZ at the baseline and after a long-term atypical antipsychotic treatment (more than 6 months) based on the resting-state functional magnetic resonance image. In total, 52 patients completed the follow-up of clinical and neuroimaging investigations. Results: At the baseline, relative to healthy controls, altered connectivities within the DMN and between the DMN and the external attention system (EAS) were observed in patients. After treatment, along with significant relief of symptoms, most FC alterations between the DMN and the EAS at the baseline were improved after treatment, although the rehabilitation of FC within the DMN was only observed at the link between the posterior cingulate cortex and precuneus. Greater reductions in negative and positive symptoms were both related to the changes of DMN-EAS FC in patients. Conclusion: Our findings provide evidence that maintenance antipsychotics on SCZ is beneficial for the improvement of DMN-EAS competitive imbalance, which may partly contribute to the efficient relapse prevention of this severe mental disorder.
| S-EPMC9171718 | biostudies-literature
Project description:BackgroundThe exosomal lncRNA-miRNA-mRNA networks in first episode schizophrenia (FOS) have not reported yet. This study examined the lncRNA, miRNA and mRNA expression level in exosome derived from first episode schizophrenia (FOS) patients, and explored the the potential of exosomes as biomarkers for schizophrenia.MethodsWe recruited 10 FOS patients and healthy controls (HCs) respectively, examined the lncRNA, miRNA and mRNA expression level of plasma exosome by high throughput sequencing, constructed lncRNA-miRNA-mRNA network, and performed correlation analysis, GO and KEGG pathway analysis, PPI network construction and ROC analysis.ResultsThere were 746 differently expressed lncRNA, 22 differently expressed miRNA, and 2637 differently expressed mRNA in plasma exosome in FOS compared with HCs. Then we constructed ceRNA network consisting of 8 down-regulated lncRNA, 7 up-regulated miRNA and 65 down-regulated mRNA, and 1 up-regulated lncRNA, 1 down-regulated miRNA and 4 up-regulated mRNA. The expression level of 1 lncRNA and 7 mRNA in exosomal network were correlated with PANSS score. GO and KEGG pathway analysis showed that 4 up-regulated mRNAs were enriched in neuropsychiatric system function. Down-regulated mRNA EZH2 and SIRT1 were identified as hub gene. Finally, we detected the ROC curve of ENSG00000251562, miR-26a-5p, EZH2, miR-22-3p, SIRT1, ENSG00000251562-miR-26a-5p-EZH2, ENSG00000251562-miR-22-3p-SIRT1, and found that the AUC of ceRNA network was higher than lncRNA, miRNA and mRNA alone.ConclusionWe constructed the lncRNA-miRNA-mRNA network in exosome derived from FOS plasma, and found that lncRNA-miRNA-mRNA network has potential as biomarkers for FOS.
| S-EPMC10441745 | biostudies-literature
Project description:Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown. The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms. Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs. Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.
| S-EPMC11293415 | biostudies-literature
Project description:Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [?20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (?50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ?350-400 ?g/L) with a response rate (?20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.
| S-EPMC6180374 | biostudies-other
Project description:BackgroundCurrently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients.MethodsRecord retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by p score.ResultsA total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60-1.10); 0.79 (0.57-1.10)] and 3-month XELOX [0.95 (0.86-1.04); 0.93 (0.83-1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63-0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events.ConclusionsThe 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.
| S-EPMC7739130 | biostudies-literature
Project description:BackgroundProbiotics are commonly used for the prevention of antibiotic-associated diarrhea (AAD). However, the optimum regimen remains controversial.ObjectiveThe objective of this article is to compare and rank the relative efficacy and tolerability among all available probiotic agents for AAD through a network meta-analysis.MethodsEligible studies were identified by searching PubMed, Embase, Medline, Cochrane library and Web of Science for randomized controlled trials (RCTs) that examined the efficacy of probiotic therapy for AAD. A random-effects model was applied within a frequentist framework. Quality of evidence was performed by the GRADE approach. The project was prospectively registered with PROSPERO (CRD 42016050776).ResultsFifty-one articles (60 comparisons, 9569 participants), including 10 probiotic interventions, were identified. Lactobacillus rhamnosus GG (LGG) had the highest probability of being ranked best both in effectiveness (odds ratio (OR), 95% confidence interval (CI) = 0.28 (0.17, 0.47)) and tolerance (0.44 (0.23, 0.84)) on prevention of AAD. With regard to reducing Clostridium difficile infection rate, Lactobacillus casei (L. casei) was considered better efficacy (0.04 (0.00, 0.77)) and medium tolerance (0.56 (0.19, 1.66)). Strain combination reported no superiority over single strain in either efficacy or tolerability.ConclusionsLGG is probably the best option to consider when AAD is indicated. L. casei appears to be the most efficacious choice when associated with severe C. difficile-related cases.
| S-EPMC5833232 | biostudies-literature