Suicide risk with selective serotonin reuptake inhibitors and other new-generation antidepressants in adults: a systematic review and meta-analysis of observational studies

2021 ◽  
pp. jech-2020-214611
Author(s):  
Michael P Hengartner ◽  
Simone Amendola ◽  
Jakob A Kaminski ◽  
Simone Kindler ◽  
Tom Bschor ◽  
...  
Keyword(s):  
Systematic Review ◽  
Suicide Attempt ◽  
Publication Bias ◽  
Serotonin Reuptake ◽  
Observational Studies ◽  
Suicide Risk ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Treatment Indications ◽  
Trim And Fill ◽  
New Generation

BackgroundThere is ongoing controversy whether antidepressant use alters suicide risk in adults with depression and other treatment indications.MethodsSystematic review of observational studies, searching MEDLINE, PsycINFO, Web of Science, PsycARTICLES and SCOPUS for case–control and cohort studies. We included studies on depression and various indications unspecified (including off-label use) reporting risk of suicide and/or suicide attempt for adult patients using selective serotonin reuptake inhibitors (SSRI) and other new-generation antidepressants relative to non-users. Effects were meta-analytically aggregated with random-effects models, reporting relative risk (RR) estimates with 95% CIs. Publication bias was assessed via funnel-plot asymmetry and trim-and-fill method. Financial conflict of interest (fCOI) was defined present when lead authors’ professorship was industry-sponsored, they received industry-payments, or when the study was industry-sponsored.ResultsWe included 27 studies, 19 on depression and 8 on various indications unspecified (n=1.45 million subjects). SSRI were not definitely related to suicide risk (suicide and suicide attempt combined) in depression (RR=1.03, 0.70–1.51) and all indications (RR=1.19, 0.88–1.60). Any new-generation antidepressant was associated with higher suicide risk in depression (RR=1.29, 1.06–1.57) and all indications (RR=1.45, 1.23–1.70). Studies with fCOI reported significantly lower risk estimates than studies without fCOI. Funnel-plots were asymmetrical and imputation of missing studies with trim-and-fill method produced considerably higher risk estimates.ConclusionsExposure to new-generation antidepressants is associated with higher suicide risk in adult routine-care patients with depression and other treatment indications. Publication bias and fCOI likely contribute to systematic underestimation of risk in the published literature.RegistrationOpen Science Framework, https://osf.io/eaqwn/

scholarly journals Suicide risk with selective serotonin reuptake inhibitors and new-generation serotonergic-noradrenergic antidepressants in adults: a systematic review and meta-analysis of observational studies

2020 ◽  
Author(s):  
Michael P Hengartner ◽  
Simone Amendola ◽  
Jakob A Kaminski ◽  
Simone Kindler ◽  
Tom Bschor ◽  
...  
Keyword(s):  
Publication Bias ◽  
Observational Studies ◽  
Suicide Risk ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Meta Analysis ◽  
Routine Care ◽  
Case Control ◽  
Risk Estimates ◽  
Trim And Fill ◽  
New Generation

Background: There is ongoing controversy whether antidepressant use alters the suicide risk in adult routine-care patients with depression and other treatment indications. The aim of this study was thus to examine the suicide risk with antidepressants in observational studies, considering financial conflicts of interest (fCOI) and publication bias. Design: Systematic review and meta-analysis. Main outcome measures: Risk of suicide, suicide attempt and/or intentional self-harm. Data sources: We searched MEDLINE, PsycINFO, Web of Science, PsycARTICLES and SCOPUS for case-control and cohort studies published 1990-2020. Eligibility criteria for study selection: Cohort and case-control studies in adults (aged >=18 years) with depression and any unspecified condition reporting suicide risk for patients exposed to selective serotonin reuptake inhibitors (SSRI) or new-generation serotonergic-noradrenergic antidepressants (SNA) relative to unexposed patients. Data extraction and analysis: Effects were aggregated with a random-effects model and reported as relative risk estimates (RE) with 95%-confidence-intervals. We assessed heterogeneity via I2-statistics and publication bias via funnel-plot asymmetry and trim-and-fill method. Study fCOI was defined present when lead-authors' professorship was industry-sponsored, they received payments from the industry, or when the study was industry-sponsored. Results: We included 27 original studies in the meta-analysis; 19 on depression (including other affective and anxiety disorders) and 8 on any unspecified condition. Use of SSRI or SNA for depression was associated with increased suicide risk (comprising both suicide and suicide attempt), RE=1.29, 1.06-1.57. Risk estimates were significantly lower in studies with fCOI (Q=21.87, p<0.001) and the trim-and-fill method estimated that 12 studies were missing due to publication bias; the result with missing studies imputed was RE=1.61, 1.31-1.99. Use of SSRI or SNA for all conditions (including depression and any unspecified condition) was associated with increased suicide risk, RE=1.43, 1.21-1.68. Studies with fCOI reported significantly lower risk estimates (Q=34.19, p<0.001) and the trim-fill method estimated that 13 studies were missing; after imputation of missing studies the result was RE=1.72, 1.44-2.05. Quality of evidence was rated very low due to substantial inconsistency of between-study results (I2>85%). Conclusions: Exposure to new-generation antidepressants is associated with increased suicide risk in adult routine-care patients with depression and other conditions. Publication bias and fCOI contribute to systematic underestimation of risk estimates in the published literature. Registration: Open Science Framework, https://osf.io/eaqwn/

Divalproex and its effect on suicide risk in bipolar disorder: A systematic review and meta-analysis of multinational observational studies

2019 ◽  
Vol 245 ◽  
pp. 812-818 ◽  
Author(s):  
Tien-Yu Chen ◽  
Masoud Kamali ◽  
Che-Sheng Chu ◽  
Chin-Bin Yeh ◽  
San-Yuan Huang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Observational Studies ◽  
Suicide Risk ◽  
Meta Analysis

Effects of the endocrine disruptor vinclozolin in male reproduction: a systematic review and meta-analysis†

2021 ◽  
Author(s):  
Mariana Feijó ◽  
Roberta V L Martins ◽  
Sílvia Socorro ◽  
Luísa Pereira ◽  
Sara Correia
Keyword(s):  
Systematic Review ◽  
Publication Bias ◽  
Meta Analysis ◽  
Endocrine Disrupting Chemicals ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Mean Differences ◽  
Trim And Fill ◽  
Meta Analyses ◽  
Q Statistic

Abstract Endocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivity was also analyzed. Statistical analysis was performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.

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