Differences in the incidence of lurasidone adverse events between depressive disorders and schizophrenia in double-blind, randomized, placebo-controlled trials: a meta-analysis

Background: 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. Objectives: The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. Methods: 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 Q χ2 test and I2 statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). Results: 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 p < 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and p = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and p = 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 p = 0.23). Conclusions: 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.

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Efficacy and safety of guselkumab for the treatment of patients with moderate-to-severe plaque psoriasis: A metaanalysis of randomized clinical trials

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i2.28 ◽

2020 ◽

Vol 19 (2) ◽

pp. 433-440

Author(s):

Xing-Bao Tao ◽

Yin-Qiu Huang ◽

Yi-Hong Zhou ◽

Lv-Lang Zhang ◽

Yao-Kai Chen

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Adverse Events ◽

Plaque Psoriasis ◽

Meta Analysis ◽

Controlled Trials ◽

Double Blind ◽

Severe Plaque Psoriasis ◽

Central Registry

Purpose: To conduct a systematic analysis on data from randomized controlled trials (RCTs) on different doses of guselkumab, and provide high-quality evidence for its use in the treatment of patients with moderate-to-severe plaque psoriasis (PsO). Methods: Related studies were searched using online search engines including MEDLINE, PubMed, and central registry of Cochrane controlled trials from January 2001 to October 2017. Only randomized, placebo-controlled, double-blind clinical trials involving guselkumab- and placebo-treated PsO subjects were included. Results: Five eligible double-blind, randomized, and placebo-controlled trials involving patients with moderate-to-severe PsO subjects treated with guselkumab were included. Compared with the placebo groups, the proportion of patients with improvements in Psoriasis Area and Severity Index (PASI) 75 (RR= 12.14; 95% CI= 9.11-16.16; p < 0.001); PASI 90 (RR= 23.26; 95% CI =14.57-37.13; p < 0.001), and PASI 100 (RR = 37.66; 95% CI = 15.81-89.69; p < 0.001) were significantly higher than those in guselkumab-treated groups. Furthermore, the guselkumab-treated groups showed significant decreases in Physician’s Global Assessment (PGA) score (RR = 10.46; 95% CI = 7.96-13.83; p < 0.001) and the Dermatology Life Quality Index (DLQI) score (SMD = -1.3; 95% CL = -1.4 to -1.19; p < 0.001), when compared with the placebo groups. However, there were no significant differences in adverse events (AEs) (RR = 1.01; 95% CL = 0.93-1.11; p > 0.05); severe adverse events (SAEs) (RR = 1.32; 95% CI =0.69-2.54; p > 0.05) and study discontinuations (RR = 0.79; 95% CI = 0.42-1.48; p > 0.05) between the two groups. Conclusion: This meta-analysis summarizes available evidence for the use of guselkumab in psoriasis. The results suggest that guselkumab is superior to placebo in moderate-to-severe psoriasis, and is welltolerated, effective, and safe in improving the severity of disease and quality of life. Keywords: Guselkumab, Effectiveness, Safety, Plaque psoriasis, Meta-analysis, Quality of life

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St John's wort for depression

The British Journal of Psychiatry ◽

10.1192/bjp.186.2.99 ◽

2005 ◽

Vol 186 (2) ◽

pp. 99-107 ◽

Cited By ~ 133

Author(s):

Klaus Linde ◽

Michael Berner ◽

Matthias Egger ◽

Cynthia Mulrow

Keyword(s):

Major Depression ◽

Depressive Disorders ◽

Meta Analysis ◽

Current Evidence ◽

Controlled Trials ◽

Clinical Effects ◽

Double Blind ◽

Beneficial Effects ◽

St John’S Wort ◽

St John's Wort

BackgroundExtracts of Hypericum perforatum (St John's wort) are widely used to treat depression. Evidence for its efficacy has been criticised on methodological grounds.AimsTo update evidence from randomised trials regarding the effectiveness of Hypericum extracts.MethodsWe performed a systematic review and meta-analysis of 37 double-blind randomised controlled trials that compared clinical effects of Hypericum monopreparation with either placebo or a standard antidepressant in adults with depressive disorders.ResultsLarger placebo-controlled trials restricted to patients with major depression showed only minor effects over placebo, while older and smaller trials not restricted to patients with major depression showed marked effects. Compared with standard antidepressants Hypericum extracts had similar effects.ConclusionsCurrent evidence regarding Hypericum extracts is inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that Hypericum has minimal beneficial effects while other trials suggest that Hypericum and standard antidepressants have similar beneficial effects.

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Efficacy and safety of extended-release amantadine in levodopa-induced dyskinesias: a meta-analysis

Neurodegenerative Disease Management ◽

10.2217/nmt-2019-0011 ◽

2019 ◽

Vol 9 (4) ◽

pp. 205-215 ◽

Cited By ~ 3

Author(s):

Azalea T Pajo ◽

Adrian I Espiritu ◽

Roland Dominic G Jamora

Keyword(s):

Adverse Events ◽

Extended Release ◽

Meta Analysis ◽

Mean Difference ◽

Controlled Trials ◽

Visual Hallucinations ◽

Efficacy And Safety ◽

Double Blind ◽

Parallel Group ◽

Troublesome Dyskinesia

Aim: To determine the effectiveness and safety of extended-release amantadine (ADS-5102) for levodopa-induced dyskinesias (LID) in patients with Parkinson disease (PD) by conducting a meta-analysis of relevant trials. Methods: The electronic databases were searched on or before March 1, 2019 for relevant trials. Only randomized, double-blind, parallel-group, placebo-controlled trials using ADS-5102 for LID in PD were included. Results: The ADS-5102 showed a reduction in the dyskinesia scores (mean difference: -9.56: CI: -10.05 to -9.07; p < 0.00001) and in the on time without troublesome dyskinesia (mean difference 2.50: CI 2.38 to 2.63; p < 0.00001). The adverse events identified in ADS-5102 were visual hallucinations, constipation, dry mouth and fall. Conclusion: ADS-5102 can be used as an adjunct therapy for LID.

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Placebo and nocebo responses in restless legs syndrome

Neurology ◽

10.1212/wnl.0000000000004004 ◽

2017 ◽

Vol 88 (23) ◽

pp. 2216-2224 ◽

Cited By ~ 28

Author(s):

Maria A. Silva ◽

Gonçalo S. Duarte ◽

Raquel Camara ◽

Filipe B. Rodrigues ◽

Ricardo M. Fernandes ◽

...

Keyword(s):

Adverse Events ◽

Restless Legs Syndrome ◽

Meta Analysis ◽

Placebo Response ◽

Controlled Trials ◽

Pool Data ◽

Double Blind ◽

Restless Legs ◽

Statistical Heterogeneity ◽

Registration Number

Objective:To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants.Methods:Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable in the placebo arm. Placebo response was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with I2 statistic. Several predetermined subgroup and sensitivity analysis were performed. PROSPERO registration number is CRD42015027992.Results:We included 85 randomized controlled trials (5,046 participants). Pooled placebo response effect size was −1.41 (95% confidence interval [CI] −1.56 to −1.25, 64 trials, I2 = 88.1%), corresponding to −6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%–50.29%, 72 trials; I2 = 89.8%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacologic interventions and idiopathic RLS, and in industry-funded and unpublished studies. The placebo response was considerably smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors.Conclusions:The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.

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Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

10.1101/2020.06.22.20136531 ◽

2020 ◽

Author(s):

Yun Zhu ◽

Zhaowei Teng ◽

Lirong Yang ◽

Shuanglan Xu ◽

Jie Liu ◽

...

Keyword(s):

Adverse Events ◽

Discharge Rate ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Serious Adverse Events ◽

Double Blind ◽

Randomized Controlled ◽

Central Register ◽

Registration Number

AbstractBACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

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Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Frontiers in Psychology ◽

10.3389/fpsyg.2021.648691 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongjiao An ◽

Changwei Wei ◽

Jing Wang ◽

Anshi Wu

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Clinical Response ◽

Clinical Remission ◽

Meta Analysis ◽

Controlled Trials ◽

Major Depressive ◽

Double Blind ◽

Madrs Score ◽

Randomized Controlled

BackgroundThere is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).MethodsWe searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery–Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.ResultsData were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (n = 858 with MDD, n = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44–7.88) in 2–4 h, 9.96 (95% CI 8.97–10.95) in 24 h, and 4.09 (95% CI 2.18–6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5–8.38, z = 2.89, and p < 0.001) for clinical remission and 3.22 (95% CI 1.85–5.61, z = 4.14, and p < 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28–2.24, z = 3.72, and p < 0.001) for clinical remission and 1.48 (95% CI 1.17–1.86, z = 3.28, and p < 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.ConclusionOur meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.Systematic Review RegistrationPROSPERO, CRD42020196856.

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The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649883 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1064-1070 ◽

Cited By ~ 76

Author(s):

Marco Cattaneo ◽

Alan S Harris ◽

Ulf Strömberg ◽

Pier Mannuccio Mannucci

Keyword(s):

Cardiac Surgery ◽

Blood Loss ◽

Meta Analysis ◽

Postoperative Blood Loss ◽

Controlled Trials ◽

Double Blind ◽

Double Blind Placebo ◽

Transfusion Requirements ◽

The Mean ◽

Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

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Effects of Teriparatide versus Salmon Calcitonin Therapy for the Treat-ment of Osteoporosis in Asia: A Meta-analysis of Randomized Controlled Trials

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320999200817114817 ◽

2020 ◽

Vol 20 ◽

Author(s):

Changjun Chen ◽

Mohammed Alqwbani ◽

Jie Chen ◽

Ruitong Yang ◽

Songgang Wang ◽

...

Keyword(s):

Femoral Neck ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Salmon Calcitonin ◽

Bone Markers ◽

Meta Analysis ◽

Controlled Trials ◽

Randomized Controlled ◽

Asian Patients ◽

Teriparatide Treatment

Objective: The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. Methods: PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis popula-tion were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthe-sis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. Results: Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in femoral neck and total hip join. There was a positive correlation between bone-specific alka-line phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. And the proportion of the occurrence of adverse effect was more obvious in teriparatide group compared with salmon calciton-in, but there was no significant difference. Conclusion: Results suggested that the use of teriparatide could improve the lumbar BMD by short-term (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

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Comparative efficacy and safety of different regimens of ranibizumab for neovascular age-related macular degeneration: a network meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2020-040906 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040906

Author(s):

Xinyu Zhao ◽

Lihui Meng ◽

Youxin Chen

Keyword(s):

Adverse Events ◽

Macular Degeneration ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Controlled Trials ◽

Cochrane Central Register ◽

Efficacy And Safety ◽

Age Related ◽

Randomised Controlled

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.

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