Antipsychotics Efficacy in Treatment of Schizophrenia Negative Symptoms: Meta-analysis of Randomized Clinical Trials

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Darbá ◽  
A. Minoves ◽  
E. Rojo ◽  
F. Jiménez ◽  
J. Rejas

Purpose:To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.Methods:Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, the Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. the outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.Results:A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. in the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.Conclusion:Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Darbá ◽  
A. Minoves ◽  
E. Rojo ◽  
F. Jiménez ◽  
J. Rejas

Purpose:To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.Methods:Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, The Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. The outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.Results:A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. In the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.Conclusion:Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.


BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e034846 ◽  
Author(s):  
Rutger MJ de Zoete ◽  
James H McAuley ◽  
Nigel R Armfield ◽  
Michele Sterling

IntroductionNeck pain is a global burdensome problem, with a large proportion of neck pain cases becoming chronic. Although physical exercise is a commonly prescribed treatment, the evidence on the effectiveness of isolated exercise interventions remains limited. Traditional pairwise randomised controlled trials (RCTs) and meta-analyses are limited in only comparing two interventions. This protocol describes the design of a network meta-analysis, which enables a comparative investigation of all physical exercise interventions for which RCTs are available. We aim to systematically compare the effectiveness of different types of physical exercise in people with chronic non-specific neck pain.Methods and analysisNine electronic databases (AMED, CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Physiotherapy Evidence Database, PsycINFO, Scopus and SPORTDiscus) were searched for RCTs from inception to 12 March 2019. Titles and abstract firstly, and full-text papers secondly, will be screened by two reviewers. Data will be extracted by two reviewers. The primary outcome measure is effectiveness of the intervention. Methodological quality of included studies will be assessed by two reviewers using the PEDro scale. The overall quality of evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, which has been adapted for network meta-analyses. The available evidence will be summarised using a network diagram. A contribution matrix will be presented to allow assessment of direct and indirect evidence. Forest plots will be constructed to visualise effects of all included exercise interventions. Pairwise effect sizes will be calculated by including all evidence available in the network. Effect measures for treatments that have not been compared in a pairwise RCT can be compared indirectly by contrasting effect sizes of comparisons with a common comparator.Ethics and disseminationThis work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal.PROSPERO registration numberCRD42019126523.


Gerontology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Qin-Yi Wang ◽  
Na Ding ◽  
Yi-He Dong ◽  
Zhang-Xin Wen ◽  
Rong Chen ◽  
...  

<b><i>Background:</i></b> The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. <b><i>Objectives:</i></b> The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. <b><i>Methods:</i></b> PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran <i>Q</i> χ<sup>2</sup> test and <i>I</i><sup>2</sup> statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). <b><i>Results:</i></b> The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and <i>p</i> &#x3c; 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and <i>p</i> = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and <i>p</i> = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and <i>p</i> = 0.23). <b><i>Conclusions:</i></b> Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.


2018 ◽  
Author(s):  
Paquito Bernard ◽  
Romain Ahmed Jérôme ◽  
Johan Caudroit ◽  
Guillaume Chevance ◽  
Carayol Marion ◽  
...  

Objective. The present meta-analysis aimed to determine the overall effect of cognitive behavior therapy combined with physical exercise (CBTEx) interventions on depression, anxiety, fatigue, and pain in adults with chronic illness; to identify the potential moderators of efficacy; and to compare the efficacy of CBTEx versus each condition alone (CBT and physical exercise). Methods. Relevant randomized clinical trials, published before July 2017, were identified through database searches in Pubmed, PsycArticles, CINAHL, SportDiscus and the Cochrane Central Register for Controlled Trials.Results. A total of 30 studies were identified. CBTEx interventions yielded small-to-large effect sizes for depression (SMC = -0.34, 95% CI [-0.53; -0.14]), anxiety (SMC = -0.18, 95% CI [-0.34; -0.03]) and fatigue (SMC = -0.96, 95% CI [-1.43; -0.49]). Moderation analyses revealed that longer intervention was associated with greater effect sizes for depression and anxiety outcomes. Low methodological quality was also associated with increased CBTEx efficacy for depression. When compared directly, CBTEx interventions did not show greater efficacy than CBT alone or physical exercise alone for any of the outcomes. Conclusion. The current literature suggests that CBTEx interventions are effective for decreasing depression, anxiety, and fatigue symptoms, but not pain. However, the findings do not support an additive effect of CBT and exercise on any of the four outcomes compared to each condition alone.


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040931
Author(s):  
Djillali Annane ◽  
Romain Pirracchio ◽  
Laurent Billot ◽  
Andre Waschka ◽  
Sylvie Chevret ◽  
...  

IntroductionThe benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock.Methods and analysisTo assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90 days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial.Ethics and disseminationThis IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access.PROSPERO registration numberCRD42017062198.


2020 ◽  
Vol 34 (8) ◽  
pp. 914-919
Author(s):  
Hiroyoshi Takeuchi ◽  
Gary Remington

Introduction: In two previous meta-analyses of randomized controlled trials (RCTs) examining antipsychotic switching strategies in patients with schizophrenia, we showed no significant differences in any clinical outcomes between immediate versus gradual and gradual versus wait-and-gradual discontinuation of the pre-switch antipsychotic. In this report, we compared immediate versus wait-and-gradual antipsychotic discontinuation. Methods: We identified five RCTs examining immediate versus wait-and-gradual discontinuation of the pre-switch antipsychotic in antipsychotic switching involving patients with schizophrenia. However, no data were available from one RCT. The following clinical outcome data were extracted and meta-analyzed: study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events that were reported in two or more of the studies. Results: The meta-analysis included four RCTs involving 351 patients ( n=175 for immediate and n=176 for wait-and-gradual antipsychotic discontinuation). A significant difference was found in study discontinuation due to all causes ( n=4, n=351, risk ratio=1.58, 95% confidence interval 1.15–2.17, p=0.005, I2=0%) between the immediate and wait-and-gradual antipsychotic discontinuation groups, while there was no significant difference in any other clinical outcomes. The group difference in study discontinuation due to all causes remained significant for the studies adopting immediate antipsychotic initiation but not for the studies switching to ziprasidone. Conclusion: Findings suggest that wait-and-gradual antipsychotic discontinuation may be preferable when a more cautious antipsychotic switch is needed. However, further long-term, double-blind RCTs are needed to confirm the present findings.


2019 ◽  
Vol 52 (01) ◽  
pp. 25-31 ◽  
Author(s):  
Marina Tsoli ◽  
Krystallenia I. Alexandraki ◽  
Maria-Eleni Spei ◽  
Gregory A. Kaltsas ◽  
Kosmas Daskalakis

AbstractMany trials have demonstrated prime antitumor activity of novel, small molecule multikinase inhibitors (MKIs) in advanced and/or metastatic thyroid cancer (TC). In this work, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, and clinicaltrials.gov databases were searched. Quality/risk of bias were assessed using GRADE criteria. Randomized clinical trials (RCTs) comparing two or more systemic therapies in patients with advanced and/or metastatic thyroid cancer were assessed. A total of 1347 articles and 548 clinical trials in clinicaltrials.gov were screened. We included seven relevant RCTs comprising 1934 unique patients assigned to different MKIs. Two separate network meta-analyses included four RCTs in radioiodine refractory well-differentiated thyroid cancer (RR-WDTC) and three RCTs in medullary thyroid cancer (MTC), respectively; all with a low risk of bias. We identified three therapies for RR-WDTC: sorafenib [disease control rate (DCR) odds ratio (OR): 0.11 (95% CI: 0.03–0.40); progression-free survival (PFS) hazard ratio (HR): 1.99 (95% CI: 1.62–2.46)], vandetanib [DCR_OR:0.26 (95% CI: 0.06–1.24); PFS_HR: 0.99 (95% CI: 0.82–1.20)] and lenvatinib [DCR_OR: 0.26 (95% CI: 0.05–1.33); PFS_HR: 0.99 (95% CI: 0.81–1.22)]; and the following therapies for MTC: vandetanib 300 mg [objective response rate (ORR)_OR: 3.31 (95% CI: 0.68–16.22); vandetanib 150 mg ORR_OR: 0.60 (95% CI: 0.16–2.33)]; and cabozantinib [ORR_OR: 85.32 (95% CI: 5.22–1395.15)]. Serious side effect (SE) analysis per organ/system demonstrated a varying MKI SE profile across both RR-WDTC and MTC diagnoses, more commonly involving metabolic/nutritional disorders [OR: 2.07 [95% CI: 0.82–5.18)] and gastrointestinal SE [OR: 1.63 (95% CI: 1.0–2.66)]. This network meta-analysis on advanced and/or metastatic TC points towards a higher efficacy of lenvatinib in RR-WDTC. The included MKIs exhibit a varying SE profile across different organs/systems favoring a patient-tailored approach with the anticipated toxicities guiding clinicians’ decisions.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Joelle Helou ◽  
Charles N Catton ◽  
Glenn Bauman ◽  
Rouhi Fazelzad ◽  
Jacques Raphael

354 Background: Recent meta-analyses suggested an improvement in overall survival (OS) with the addition of Abiraterone (A) vs Docetaxel (D) to androgen deprivation therapy (ADT) in the treatment of men with metastatic castration-sensitive prostate cancer. However, none have reported castration resistance-free survival (CFS) and toxicity data; two clinically relevant outcomes for physicians and patients. Methods: We conducted a systematic review and meta-analysis to assess CFS and toxicity of adding A or D to ADT in men with castration-sensitive prostate cancer. The electronic databases Ovid MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE, were searched for randomized controlled trials. Pooled hazard ratios (HR) for CFS, and pooled risk ratios (RR) for grade 3 or higher toxicity were analyzed using the Mantel-Haenszel method and generic inverse variance. To account for between-studies heterogeneity, random-effect models were used to compute pooled estimates. Subgroup analyses compared patients on A and D in terms of CFS. Results: Five studies were included. The addition of A or D to ADT decreased the risk of development of castration-resistance by 53% (5 studies, 4,462 participants, HR = 0.47, 95% CI 0.33-0.67). In a subgroup analysis, the addition of A seemed to be better than D for the outcome CFS (5 studies, HR = 0.31, 95% CI 0.27-0.34 versus HR = 0.62, 95% CI 0.56-0.69, test for subgroup difference, p< 0.001). Different profiles of toxicity were seen with A and D. While A increased the risk of hypokalemia (3,107 participants, HR = 6.63, 95% CI 3.5-12.5) and cardiac toxicity (3,107 participants, HR = 2.4, 95% CI 1.7-3.3), D increased the risk of neutropenia (2,151 participants, HR = 13, 95% CI 8.9-18.8) and neuropathy (2,151 participants, HR = 2.25, 95% CI 1.18-4.3). Conclusions: The addition of A and D to ADT increases CFS in men with castration-sensitive prostate cancer, with a longer CFS noted for A compared to D. Considering CFS and OS, A may be preferred to D as initial therapy. Toxicity profiles differed between A and D. Quality of life and cost differences between A and D are other important factors and were not considered in this analysis.


2016 ◽  
Vol 47 (3) ◽  
pp. 414-425 ◽  
Author(s):  
K. Kamenov ◽  
C. Twomey ◽  
M. Cabello ◽  
A. M. Prina ◽  
J. L. Ayuso-Mateos

BackgroundThere is growing recognition of the importance of both functioning and quality of life (QoL) outcomes in the treatment of depressive disorders, but the meta-analytic evidence is scarce. The objective of this meta-analysis of randomized controlled trials (RCTs) was to determine the absolute and relative effects of psychotherapy, pharmacotherapy and their combination on functioning and QoL in patients with depression.MethodOne hundred and fifty-three outcome trials involving 29 879 participants with depressive disorders were identified through database searches in Pubmed, PsycINFO and the Cochrane Central Register of Controlled Trials.ResultsCompared to control conditions, psychotherapy and pharmacotherapy yielded small to moderate effect sizes for functioning and QoL, ranging from g = 0.31 to g = 0.43. When compared directly, initial analysis yielded no evidence that one of them was superior. After adjusting for publication bias, psychotherapy was more efficacious than pharmacotherapy (g = 0.21) for QoL. The combination of psychotherapy and medication performed significantly better for both outcomes compared to each treatment alone yielding small effect sizes (g = 0.32 to g = 0.39). Both interventions improved depression symptom severity more than functioning and QoL.ConclusionDespite the small number of comparative trials for some of the analyses, this study reveals that combined treatment is superior, but psychotherapy and pharmacotherapy alone are also efficacious for improving functioning and QoL. The overall relatively modest effects suggest that future tailoring of therapies could be warranted to better meet the needs of individuals with functioning and QoL problems.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wei Jiang ◽  
Shaojun Liao ◽  
Xiankun Chen ◽  
Cecilia Stålsby Lundborg ◽  
Gaetano Marrone ◽  
...  

Background. Depression is a debilitating comorbidity of heart failure (HF) that needs assessment and management. Along with mind-body exercise to deal with HF with depression, the use of TaiChi and/or Qigong practices (TQPs) has increased. Therefore, this systematic review assesses the effects of TQPs on depression among patients with HF. Methods. Randomized controlled trials (RCTs) that examined the effect of TQPs on depression in patients with HF were searched by five databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI)). With standardized mean difference (SMD) and 95% confidence intervals (95% CI), random-effects meta-analyses of the effect of TQPs on depressive symptoms were performed. Results. Of eight included RCTs, seven (481 patients) provided data for the meta-analysis. The pooling revealed that TQPs contribute to depression remission in HF (SMD −0.66; 95% CI −0.98 to −0.33, P < 0.0001 ; I2 = 64%). Its antidepressive effect was not influenced by intervention duration or exercise setting, but rather by ejection fraction subtype, depressive severity, and depression instruments. The beneficial effects were preserved when the study with the largest effect was removed. Conclusion. This study suggests that TQPs might be a good strategy for alleviating depressive symptoms in patients with HF. And rigorous-design RCTs, which focus on the identified research gaps, are needed to further establish the therapeutic effects of TQPs for depression in HF.


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