Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

2021 ◽  
pp. 1-10
Author(s):  
Lena Rink ◽  
Anne Adams ◽  
Cora Braun ◽  
Tom Bschor ◽  
Kathrin Kuhr ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Major Depressive ◽  
Meta Analyses ◽  
Higher Doses ◽  
Norepinephrine Reuptake

<b><i>Introduction:</i></b> Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. <b><i>Objective:</i></b> This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. <b><i>Methods:</i></b> A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). <b><i>Results:</i></b> From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. <b><i>Conclusion:</i></b> Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

scholarly journals Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis

2014 ◽  
Vol 44 (14) ◽  
pp. 2927-2937 ◽  
Author(s):  
Y.-J. Zhao ◽  
M.-Y. Du ◽  
X.-Q. Huang ◽  
S. Lui ◽  
Z.-Q. Chen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Anterior Cingulate Cortex ◽  
Grey Matter ◽  
Meta Analysis ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Major Depressive ◽  
Meta Regression ◽  
Meta Analyses

BackgroundBecause cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.MethodA systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.ResultsA total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.ConclusionsBy excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal–limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

scholarly journals Alcohol consumption and incidence of prostate cancer among Chinese people: A systematic review and meta-analysis

2020 ◽  
Vol 8 (1) ◽  
pp. 12-28
Author(s):  
Jinhui Zhao ◽  
Di Gao ◽  
Yanhui Li ◽  
Tim Stockwell ◽  
Jun Ma
Keyword(s):  
Prostate Cancer ◽  
Alcohol Consumption ◽  
Dose Response ◽  
Alcohol Intake ◽  
Meta Analysis ◽  
Chinese Language ◽  
Response Relationship ◽  
Chinese People ◽  
Dose Response Relationship ◽  
Meta Analyses

Aims: Meta-analyses have suggested a dose-response relationship between level of alcohol use and risk of prostate cancer, but the populations in the included studies are predominantly Caucasian. Many Chinese language studies have not been included in published reviews and/or meta-analyses. The present meta–analysis accessed research reports in both English and Chinese language sources in order to investigate this relationship specifically among Chinese people. Methods: Searches in five large Chinese biomedical bibliographic databases were made for case–control and cohort studies of alcohol consumption and prostate cancer incidence and death (ICD–10: C61) up to May 2017. Studies were coded for design, outcome, drinker and non-drinkers, extent of control for confounding and other study characteristics. Mixed models were used to estimate relative risk (RR) of incidence or death from prostate cancer due to alcohol consumption with study level controls for designs, drinker bias and types of drinkers. Findings: A total of 415 studies were identified of which 25 (20 in Chinese from five Chinese databases and 5 in English from published meta-analyses) satisfied inclusion criteria providing 36 risk estimates of prostate cancer for drinkers versus non-drinkers. There was a total of 36 OR estimates; 27 using patients as controls and 9 using healthy people. Nine studies (14 OR estimates) specified reference abstainers as “never drank” or “no drinking”. Adjusted RR estimates indicated a significantly increased risk of prostate cancer among drinkers (RR=1.46, 95% CI: 1.40 – 1.52, t-test P<0.001) compared to non-drinkers. Dose-response relationships (t-test P<0.001) were evident in three studies that assessed level of alcohol intake. Conclusions: There is a significantly higher risk of prostate cancer incidence among Chinese drinkers than non-drinkers, with some evidence of a dose-response relationship. However, almost all the identified studies suffered from former and/or occasional drinker biases. Few studies had adequate measures of level of alcohol intake and further well-designed studies are required.

scholarly journals The level of bilirubin and the risk of ischemic stroke: a systematic review and dose-response meta-analysis of real-world studies

2020 ◽  
Author(s):  
Xiao Wang ◽  
Yang Zhou ◽  
Xiaofei Ye ◽  
Fangchen Liu ◽  
Xi Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Secondary Outcome ◽  
Serum Total Bilirubin ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Meta Analyses ◽  
The Relationship

Abstract Background: Bilirubin, a marker of hepatic and hematological diseases in clinical practice, is not only a waste end-product but also an antioxidant that may protect against diseases associated with oxidative stress. Numerous epidemiological studies have shown an inverse relationship between the serum total bilirubin (TBIL) level and the risk of ischemic stroke (IS). However, markedly elevated TBIL levels may exert neurotoxic effects. Based on this, we conducted a dose-response meta-analysis to quantify the relationship between blood TBIL and IS as well as between TBIL and all types of stroke (AS) in the physiological range of bilirubin.Methods: PubMed, Embase, Web of Science, and Cochrane Central databases were searched up to March 2019. Additional studies were identified by reviewing references and contacting authors. Categorical and dose-response meta-analyses were performed to quantify the relationship between TBIL and IS. The primary outcome was ischemic stroke, and the secondary outcome was all types of stroke.Results: Nine observational studies (seven publications) involving 110,032 participants and 3710 stroke cases were included for analysis. The average OR of IS for every 1 µmol/L increment in TBIL level was 0.978 (95% CI: 0.957–0.999). The summary OR of AS for every 1 µmol/L increment in TBIL level was 0.974 (95% CI: 0.956–0.992). Subgroup analysis based on gender showed a negative dose-response relationship between the circulating TBIL level and IS or AS in males, but not in females.Conclusions: The present study found a negative dose-response relationship between the circulating TBIL level and the risk of IS or AS within physiologic range of serum TBIL in males. Moderately elevated blood TBIL levels might be associated with a diminished prevalence of IS. Every 1 µmol/L increment in serum TBIL level was associated with a 2.2% decrease in the risk of IS and a 2.6% decrease in the risk of AS. However, due to the limitations in the number of included studies and their quality, large-scaled prospective cohort studies are needed to confirm the conclusion of the current analysis.Trial registration: This study was registered at PROSPERO (https://www.crd. york.ac.uk/PROSPERO/[CRD42017075988]).

scholarly journals The level of Bilirubin and the risk of ischemic stroke: a systematic review and dose-response meta-analysis of real-world studies

2019 ◽  
Author(s):  
Xiao Wang ◽  
Yang Zhou ◽  
Xiaofei Ye ◽  
Fangchen Liu ◽  
Xi Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Secondary Outcome ◽  
Serum Total Bilirubin ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Meta Analyses ◽  
The Relationship

Abstract Background: Bilirubin, a marker of hepatic and hematological diseases in clinical practice, is not only a waste end-product but also an antioxidant that may protect against diseases associated with oxidative stress. Numerous epidemiological studies have shown an inverse relationship between the serum total bilirubin (TB) level and the risk of ischemic stroke (IS). However, markedly elevated TB levels may exert neurotoxic effects. Based on this, we conducted a dose-response meta-analysis to quantify the relationship between blood TB and IS as well as between TB and all types of stroke (AS) in the physiological range of bilirubin.Methods: PubMed, Embase, Web of Science, and Cochrane Central databases were searched up to March 2019. Additional studies were identified by reviewing references and contacting authors. Categorical and dose-response meta-analyses were performed to quantify the relationship between TB and IS. The primary outcome was ischemic stroke, and the secondary outcome was all types of stroke.Results: Nine observational studies (seven publications) involving 110,032 participants and 3710 stroke cases were included for analysis. The average OR of IS for every 1 µmol/L increment in TB level was 0.978 (95%CI: 0.957–0.999). The summary OR of AS for every 1 µmol/L increment in TB level was 0.974 (95%CI: 0.956–0.992). Subgroup analysis based on gender showed a negative dose-response relationship between the circulating TB level and IS or AS in males, but not in females.Conclusions: The present study indicates a negative dose-response relationship between the circulating TB level and the risk of IS or AS within physiologic range of serum TB in males. Moderately elevated blood TB levels were associated with a diminished prevalence of IS. Every 1 µmol/L increment in serum TB level was associated with a 2.2% decrease in the risk of IS and a 2.6% decrease in the risk of AS. Large-scaled prospective studies are needed to confirm the conclusion of the current analysis.Trial registration: This study was registered at PROSPERO(https://www.crd. york.ac.uk/PROSPERO/[CRD42017075988]).

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