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Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: A population-based cohort study.

ABSTRACT: To estimate the risk of gastrointestinal (GI) bleeding associated with serotonin reuptake inhibitors (SSRIs) by level of kidney function.We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified patients with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml min-1 1.73 m-2 for ?3 months), and a comparison group of patients without it. Patients with CKD were further classified as stage 3a (eGFR 45-59 ml min-1 1.73 m-2 ), 3b (30-44 ml min-1 1.73 m-2 ) and 4/5 (<30 ml min-1 1.73 m-2 ). We excluded prevalent SSRI users at cohort entry. Exposure was time-dependent SSRI prescription and outcome was first hospitalization for GI bleeding. We estimated adjusted rate ratio (aRR) and rate difference (aRD) of GI bleeding comparing periods with and without SSRI prescription at each level of kidney function.The aRRs and aRDs were: (i) no CKD (n = 202?121) aRR: 1.66 (95%CI 1.37-2.01), aRD: 2.0/1000 person-years (5.5 vs. 3.5/1000 person-years in period with and without SSRIs); (ii) CKD stage 3a (n = 153?316) aRR: 1.86 (1.62-2.15), aRD: 4.2/1000 person-years (8.3 vs. 4.1/1000 person-years); (iii) CKD stage 3b (n = 46?482) aRR: 1.61 (1.27-2.04), aRD: 4.8/1000 person-years (9.9 vs. 5.1/1000 person-years); and (iv) CKD stage 4/5 (n = 11?197) aRR: 1.84 (1.14-2.96), aRD: 7.9/1000 person-years (15.3 vs. 7.4/1000 person-years). While there was no evidence of increase in the aRR (P = 0.922), there was strong evidence that the aRD increased as kidney function deteriorated (P = 0.001).While the relative risk was constant, the excess risk of GI bleeding associated with SSRIs markedly increased among patients with decreased kidney function.

SUBMITTER: Iwagami M

PROVIDER: S-EPMC6089824 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: A population-based cohort study.

Iwagami Masao M Tomlinson Laurie A LA Mansfield Kathryn E KE Douglas Ian J IJ Smeeth Liam L Nitsch Dorothea D

British journal of clinical pharmacology 20180708 9

<h4>Aim</h4>To estimate the risk of gastrointestinal (GI) bleeding associated with serotonin reuptake inhibitors (SSRIs) by level of kidney function.<h4>Methods</h4>We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified patients with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml min<sup>-1</sup> 1.73 m<sup>-2</sup> for ≥3 months), and a comparison group of patients without it. Patients with CKD we ...[more]

PMID: 29864791

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Project description:BackgroundAlthough selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain.Methods and findingsFrom Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08-1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19-1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25-34 y (HR = 1.20, 95% CI 0.95-1.52, p = 0.125, absolute risk = 1.6%), in those aged 35-44 y (HR = 1.06, 95% CI 0.83-1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84-1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16-1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10-1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07-1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22-1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76-2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13-1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08-2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors.ConclusionsThe association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.

Project description:BackgroundAnxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis.Methods and findingsWe searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials.ConclusionsIn this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.

Project description:ImportanceSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized.ObjectivesTo assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk.Design, setting, and participantsA population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration.ExposuresConcomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone.Main outcomes and measuresThe main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding.ResultsThere were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47).Conclusions and relevanceThis study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

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Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: A population-based cohort study.

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Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: A population-based cohort study.

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