Selective Serotonin Reuptake Inhibitors Users Research Articles

SSRI use during acute COVID-19 and risk of long COVID among patients with depression

BackgroundLong COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.MethodsIn an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.ResultsWe analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).ConclusionsThese findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Poor muscle health and cardiometabolic risks associated with antidepressant treatment.

This study aims to investigate whether antidepressant users display differences in fat distribution and muscle composition relative to non-users and to explore risk factors for developing cardiovascular disease (CVD) and type 2 diabetes. The study used quantitative adipose and muscle tissue measures derived from magnetic resonance imaging data from UK Biobank (N = 40,174). Fat distribution and muscle composition of selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) users were compared with sex-, age-, and BMI-matched control individuals. Cox regression models were used to test for increased risk of developing CVD and type 2 diabetes. SSRI users had more visceral fat, smaller muscle volume, and higher muscle fat infiltration compared with matched control individuals. Female users showed a larger increase in BMI over time compared with male users. However, male users displayed an unhealthier body composition profile. Male SSRI users also had an increased risk of developing CVD. Both male and female TCA users showed lower muscle volume and an increased risk of developing type 2 diabetes. Adverse changes in body composition of antidepressant users are not captured by tracking the body weight or the BMI of the patients. These changes may lead to a worsened cardiometabolic risk profile.

Comparison of the Effect of Selective Serotonin and Norepinephrine Reuptake Inhibitors on Bone Mineral Density with Selective Serotonin Reuptake Inhibitors and Healthy Controls

Purpose: This study investigated the association between selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) use and the risk of decreased bone mineral density in postmenopausal women.Methods: Sixty-three patients diagnosed with GAD (Generalized Anxiety Disorder) were treated with venlafaxine or duloxetine from the SNRI group, and sixty patients treated with SSRIs were enrolled. Social demographic features, the Hamilton Anxiety Scale (HAS) results, and the Hamilton Depression Scale (HDS) scores of all the patients were assessed. The BMD (bone mineral density) of the patients was measured by dual-energy X-ray absorptiometry (DXA) at the femoral and lumbar regions. The BMD of the patients was compared with that of 40 healthy controls.Results: Bone measurements in the SNRI and SSRI users were similar to those of the healthy controls. However, osteopenic values were observed in the SSRI users, while normal bone density was found in the SNRI users. Also, the bone mineral densities were compared between patients using duloxetine and venlafaxine with healthy controls, showing similar T-score and Z-score values with no significant differences compared to the control group. However, while the lumbar region T-scores of those using duloxetine were within normal values, they were within the osteopenia range of venlafaxine and healthy controls.Conclusion: SNRIs may have a lower risk of developing osteoporosis than SSRIs. Of the SNRIs, duloxetine appears to be safer than venlafaxine. Further randomized controlled studies are warranted to determine whether SNRI use is risky.

Exploring The Relationship Between SSRIs, Falls, Fractures, And Bone Mineral Density In Older Irish Adults: Results From The TUDA Study

Abstract Background Selective Serotonin Reuptake Inhibitors (SSRIs) are associated with an increased risk of falls and fractures, though the results from studies are inconsistent. SSRIs may cause a decline in bone mineral density (BMD), but this remains unclear. We aimed to explore the relationship between SSRI use and falls, fractures and BMD in older Irish adults. Methods Study participants were from a cross-sectional study of adults aged >60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Falls and falls resulting in fracture in the preceding year were self-reported so participants with an MMSE < 24 were excluded. The relationship between SSRIs and falls and falls with fractures was explored in multivariate logistic regression adjusting for relevant covariates and medications: loop and thiazide diuretics, alpha and beta blockers, calcium channel blockers, ACE-inhibitors, benzodiazepines, opioids. In a subgroup with no prior diagnosis of osteoporosis or on medications for same, the relationship with SSRI's and BMD (as assessed with DXA) was explored. Results There were 4521 participants, 67.6% female, mean age 73.3 ± 8.1 years, 9.4% (n=427) using SSRIs. SSRI use predicted an increased risk of falls in the last year both before and after multivariate adjustment (OR 1.71, 1.37-2.14, p<0.001). In participants with falls (n=1448), those who had a fall with fracture versus a fall with no fracture were no more likely to be using SSRIs. In a subsample, (n=2178) no relationship was found between SSRI use and BMD at the hip, neck of femur or spine. Conclusion SSRIs use was associated with a 71% increased risk of falls though did not predict BMD or fractures. However, duration of SSRI use was not known and there was no prospective follow up. It remains unclear whether increased fracture risk in SSRI users found elsewhere is explained solely by falls risk.

Dose-dependent increase in risk of bleeding and bleeding complications in relation to SSRI use at delivery

IntroductionDepression during pregnancy is a severe state that increases the risk of suicide, as well as adverse newborn outcomes. Selective serotonin re-uptake inhibitors (SSRIs) are effective for the treatment of depression, but increase the risk of bleeding complications at delivery. Knowledge on the dose dependency of this association is lacking. MethodsA hospital-based cohort study of all women who gave birth at Karolinska University Hospital in Stockholm over the 5-year period from 2007 to 2011, with or without SSRI use, was undertaken. In total, 334 women who delivered vaginally and were exposed to SSRIs at delivery were identified. All other women who delivered vaginally formed the control group (n = 31,929). The electronic maternal health records of the 334 SSRI users were scrutinized, and the women were categorized into two groups: moderate (n = 246) or high (n = 88) SSRI dose at delivery. The main outcome was bleeding complications at delivery in relation to SSRI dose. ResultsA dose-dependent increase in the rate of postpartum haemorrhage (≥1000 ml) was found, affecting 8.4 %, 14.6 % and 23.9 % (p ≤ 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. In addition, a dose-dependent increase in the rate of postpartum anaemia was found, affecting 7.0 %, 9.3 % and 15.9 % (p = 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. Mean blood loss of 406 ml, 483 ml and 482 ml (p ≤ 0.001) was found in the control group, the moderate-dose group and the high-dose group, respectively. Women exposed to SSRIs delivered earlier, but did not have higher prevalence of pre-eclampsia compared with the control group. ConclusionsThe dose-dependent relationship between SSRIs and bleeding complications may be clinically useful in the management of this vulnerable group of women.

Risk of dementia among antidepressant elderly users: A population-based cohort analysis in Spain

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624–2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818–2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance.Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed.

Dose of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding in older adults.

Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of upper gastrointestinal bleeding (UGIB) in older patients but little is known about the risk associated with individual SSRI drugs and doses. To quantify the risk of UGIB in relation to individual SSRI use in older adults. We conducted a nested case-control study within a cohort of 9565 patients aged ⩾65 years prescribed SSRIs from 2000 to 2013 using claims data of universal health insurance in Taiwan. Incident cases of UGIB during the follow-up period were identified and matched with three control subjects. Conditional logistic regression was used to estimate the odds ratio (OR) of UGIB associated with individual SSRI use and cumulative dose. UGIB risk increased with the increasing cumulative doses of SSRIs (adjusted OR: 1.28, 95% confidence interval (CI): 1.02-1.62 for the highest vs. the lowest tertile). Compared with users of other SSRIs, fluoxetine users were at an increased risk of UGIB (adjusted OR: 1.25, 95% CI: 1.03-1.50) with a dose-response manner, whereas paroxetine users had 29% decreased odds (95% CI: 0.56-0.91). The increased risk was only observed among current fluoxetine users. Fluoxetine therapy was associated with an increased risk of UGIB in a dose-response manner among older adults.

Selective Serotonin Reuptake Inhibitors and Risk of Gastrointesinal Bleeding In Dyspepsia: An Evidence-Based Case Report

Aim: This evidence-based case report aims to provide the latest evidence about the risk of gastrointesinal (GI) bleeding in selective serotonin reuptake inhibitor (SSRI) users with dyspepsia.Method: The literature search was conducted in four major electronic databases (PubMed, Cochrane, Scopus, ProQuest). The selected articles were sorted through screening abstract based on the inclusion and exclusion criteria. Critical appraisal was performed by using validated critical appraisal tool.Results: Of 247 records from extensive literature searching, three eligible studies (one randomized clinical trial and two cohort studies) were obtained to answer the clinical question. All studies showed SSRIs did not increase the risk of GI bleeding in patients with functional dyspepsia and peptic ulcer. However, the adverse event of SSRIs might be under-reported.Conclusion: According to the evidence, the risk of GI bleeding in SSRIs users with dyspepsia is still unclear. Larger size of sample of controlled trial study is recommended to be conducted to calculate the precise risk of GI bleeding in SSRI users with dyspepsia.

Association between selective serotonin reuptake inhibitor use and developing irritable bowel syndrome through retrospective analysis.

Serotonin affects the balance and integrity of the gut microbiome; however, studies have confirmed the influence of selective serotonin reuptake inhibitors (SSRIs) on irritable bowel syndrome (IBS). We evaluated the association between SSRI use and subsequent IBS occurrence in a real-world setting. A multivariate Cox proportional hazard model was adopted, and the National Health Insurance Service cohort claims database between 2010 and 2019 was used. Non-SSRI users were selected using the propensity score matching method. Subgroup analyses were performed using the point of use, cumulative dose, and duration of SSRI use. Additional analysis was performed using a control group without psychiatric medications. We included 2901 SSRI users and 2727 non-SSRI users. After adjusting covariates, the risk of developing IBS in SSRI users was 1.54 times that in non-SSRI users (95% confidence interval [CI]: 1.01-2.33). The hazard ratio (HR) of the recent, heavy, and short-term user groups were 3.19 (95% CI: 2.03-4.99), 2.22 (95% CI: 1.50-3.29), and 4.83 (95% CI: 3.02-7.73), respectively, compared with that of non-users. In patients without a history of psychiatric medications, the risk of IBS incidence after SSRI use increased significantly (HR: 1.61, 95% CI: 1.06-2.42), whereas HR was insignificant in patients with a history of psychiatric medications (HR: 1.25, 95% CI: 0.98-1.60). The risk of subsequent IBS occurrence following SSRI use was high in patients who initially took a heavy SSRI dose and those who did not have a history of psychiatric drug use.

Selective Serotonin Reuptake Inhibitors (SSRI) and Dental Implant Failure: A Systematic Review and Meta-Analysis.

Selective Serotonin Reuptake Inhibitors (SSRI) are commonly prescribed to treat mental health disorders, and although scarce, previously published literature has shown a significant association between SSRI use and dental implant failure. This systematic review and meta-analysis aimed to examine if such association exists, and if so, determine its strength. Reviewers performed an extensive search of the literature, last accessed June 2022 in PubMed/Medline, Embase, and Cochrane databases using MeSH terms. Retrospective and prospective observational cohort and experimental studies that evaluated the role of SSRI on dental implant failure among individuals≥18 years of age, with a minimum follow-up of 6 months after implant placement, were deemed eligible. The search yielded a total of six eligible studies, all retrospective cohorts. The statistical analyses were performed using the statistical software R 4.1.3. Results showed higher implant failure rates among SSRI users vs. non-SSRI users at both patient level (5.6-19.6% vs. 1.9-8.0%) and at implant level (5.6-12.5% vs. 1.9-5.8%). The pooled relative risk (pooled-RR) of implant failure was more than double among SSRI users at patient (pooled-RR: 2.44, 95% CI : 1.68-3.55, p <0.01) and implant levels (pooled-RR: 2.34, 95% CI : 1.74-3.15, p <0.01) compared to non-SSRI users. DerSimonian and Laird estimates showed homogeneity of the studies ( I 2 =0%, p >0.05), and funnel plots and Egger's test determined no publication bias across all selected studies at both patient and implant levels. In conclusion, SSRI use is significantly associated with higher implant failure. Providers should be aware of this association and educate their patients on their risk of implant therapy when obtaining informed consent.

Reasons for Discontinuation or Change of Selective Serotonin Reuptake Inhibitors in Online Drug Reviews

Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed medication class to treat a variety of mental disorders. However, adherence to SSRIs is low, and uncovering the reasons for discontinuation among SSRI users is an important first step to improving medication persistence. To identify the reasons SSRIs are discontinued or changed, as reported by patients and caregivers in online drug reviews. This qualitative study used natural language processing and machine learning to extract mentions of changes in SSRI intake from 667 drug reviews posted on the online health forum WebMD from September 1, 2007, to August 31, 2021. The type of medication change, including discontinuation, switch to another medication, or dose change and the reason for the change were manually annotated. In each instance in which an adverse event was reported, the event was categorized using Medical Dictionary for Regulatory Activities primary system organ class (SOC) codes, and its relative frequency was compared with that in spontaneous reporting systems maintained by the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency. Reasons for SSRI medication change as assessed using SOC codes. In total, 667 reviews posted by 659 patients or caregivers (516 [78%] of patients were female; 410 [62%] 25-54 years of age) were identified that indicated a medication change: 335 posts indicated SSRI discontinuation, 188 posts indicated dose change, and 179 posts indicated switched medications. Most authors 625 (95%) were patients. The most common reason for medication discontinuation or switching was adverse events experienced, and the most common reason for dose change was titration. Both uptitration and downtitration were initiated by either a health care professional or patient. The most common adverse events were classified by SOC codes as psychiatric disorders, including insomnia, loss of libido, and anxiety. Compared with those in regulatory data, psychiatric adverse events, adverse events recorded by investigations (mostly weight gain) and adverse events associated with the reproductive system (mostly erectile dysfunction) were reported disproportionately more often. This qualitative study of online drug reviews found that useful information was provided directly by patients or their caregivers regarding their medication behavior, specifically, information regarding SSRI treatment changes that may inform interventions to improve adherence. These findings suggest that these reported adverse events may be associated with SSRI persistence and that people may feel more inclined to report such events on social media than to clinicians or regulatory agencies.

Pre-intensive care unit use of selective serotonin reuptake inhibitors and mortality in critically ill adults with mental disorders: analysis from the MIMIC-IV database

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mental disorders in critically ill patients. We performed a retrospective cohort study to investigate the association between pre-ICU use of SSRIs and mortality in critically ill adults with mental disorders. We identified critically ill adults with mental disorders based on the Medical Information Mart in Intensive Care-IV database. The exposure was the use of SSRIs during the period after hospital admission and before ICU admission. The outcome was in-hospital mortality. Time-dependent Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI). To further test the robustness of the results, we performed propensity score matching and marginal structural Cox model estimated by inverse probability of treatment weighting. The original cohort identified 16601 patients. Of those, 2232 (13.4%) received pre-ICU SSRIs, and 14369 (86.6%) did not. Matched cohort obtained 4406 patients, with 2203 patients in each group (SSRIs users vs. non-users). In the original cohort, pre-ICU use of SSRIs was associated with a 24% increase in the hazard for in-hospital mortality (aHR, 1.24; 95% CI, 1.05–1.46; P = 0.010). The results were robust in the matched cohort (aHR, 1.26; 95% CI, 1.02–1.57; P = 0.032) and the weighted cohort (aHR, 1.43; 95% CI, 1.32–1.54; P < 0.001). Pre-ICU use of SSRIs is associated with an increase in the hazard for in-hospital mortality in critically ill adults with mental disorders.

Periodontal and peri-implant status and whole salivary interleukin 1-beta levels among individuals using selective serotonin reuptake inhibitors: an observational study

ObjectiveSelective serotonin reuptake inhibitors (SSRI) are commonly used for managing psychological diseases such as depression. These disorders are also directly associated with periodontal and peri-implant diseases, namely periodontitis and peri-implantitis, respectively. It is hypothesized that there is no difference in periodontal and peri-implant clinicoradiographic status and unstimulated whole salivary interleukin (IL)-1β levels in participants using selective serotonin reuptake inhibitors (SSRI) and controls (individuals not using SSRI). The aim of the present observational case-control study was to compare periodontal and peri-implant clinicoradiographic statuses and whole salivary IL-1β in participants using SSRI and controls.MethodsUsers of SSRI and controls were included. In all participants, periodontal (plaque index [PI], gingival index [GI], probing depth [PD], clinical attachment loss [AL] and marginal bone loss [MBL]) and peri-implant (modified PI [mPI], modified GI [mGI], PD and crestal bone loss [CBL]) were assessed. Unstimulated whole saliva was collected and IL-1β levels were determined. Information related to duration of implants in function, duration of depressive symptoms and treatment of depression was retrieved from healthcare records. Sample-size was estimated using 5% error and group comparisons were performed. P < 0.05 was considered statistically significant.ResultsThirty-seven SSRI users and 35 controls were assessed. Individuals using SSRI had a history of depression of 4.2 ± 2.5 years. The mean age of SSRI-users and controls were 48.7 ± 5.7 and 45.3 ± 5.1 years, respectively. Tooth brushing twice daily was reported by 75.7% and 62.9% SSRI-users and controls, respectively. There was no statistically significant difference in PI, mPI, GI, mGI, PD, clinical AL, numbers of MT and mesial and distal MBL and CBL among individuals using SSRI compared with controls (Tables 3 and 4). The unstimulated whole salivary flow rate in individuals using SSRI and controls was 0.11 ± 0.003 and 0.12 ± 0.001 ml/min, respectively. Whole salivary IL-1β levels in individuals using SSRI and controls were 57.6 ± 11.6 pg/ml and 34.6 ± 5.2 pg/ml, respectively.ConclusionUsers of SSRI and controls demonstrate healthy periodontal and peri-implant tissue statuses with no marked differences in whole salivary IL-1β levels provided oral hygiene is stringently maintained.

COVID-19 mortality among selective serotonin reuptake inhibitor users—results from a nationwide cohort

ObjectiveTo examine differences in mortality and/or severe acute respiratory syndrome between selective serotonin reuptake inhibitor- (SSRI) users and non-SSRI users up to 60 days after a positive SARS-CoV-2 real-time reverse transcription PCR test. MethodsRetrospective cohort study including all Danish residents above the age of eighteen with a positive SARS-CoV-2 PCR test from 26 February, 2020 to 5 October, 2021. The follow-up period was 60 days. The primary outcome was all-cause mortality, and the secondary outcome was severe acute respiratory syndrome. Exposure of interest was SSRI use. Differences between SSRI users and non-users were examined with Cox regression. ResultsAltogether, 286,447 SARS-CoV-2 positive individuals were identified, and 7113 met the criteria for SSRI use. SSRI users had a mean age of 50.4 years, and 34% were males. Non-SSRI users had a mean age of 41.4 years, and 50% were males. Similar vaccination frequency was observed among the two groups. Sertraline was the most commonly used SSRI, followed by citalopram and escitalopram. We found 255 deaths among SSRI users (3.6%) and 2872 deaths among non-SSRI users (1.0%). SSRI use was significantly associated with increased mortality, with a hazard ratio of 1.32 (95% confidence interval, 1.16 –1.50; p 0.015), even when adjusting for age, sex, vaccination status, and comorbidities. DiscussionWe found significantly higher mortality when comparing SSRI users to non-SSRI users within 60 days after a positive SARS-CoV-2 PCR test. Even when considering possible residual confounding, a positive effect of SSRI intake seems highly unlikely. Our study therefore speaks against the hypothesis of repurposing SSRI drugs for COVID-19 treatment.

Association of selective serotonin reuptake inhibitor use with marginal bone level changes around osseointegrated dental implants: A retrospective study.

Selective serotonin reuptake inhibitors (SSRIs) are used for the management of anxiety and depression. Existing evidence shows their negative impact on implant osseointegration, survival rates, and peri-implant health. Currently, there are limited data on their effect on peri-implant marginal bone levels. The primary goal of this retrospective study is to evaluate the association between SSRIs use and marginal bone level (MBL) changes around osseointegrated dental implants over time. Records from patients who received at least one dental implant between 2010 and 2021 were reviewed. Information related to medical history, SSRI use, and the implant site was obtained from patients' electronic charts. Mesial and distal MBLs were measured relative to the implant platform on digital intraoral radiographs, taken at the time of prosthesis installation and at the most recent follow-up visit. MBL changes were calculated. A total of 152 dental implants from 105 patients were included. The mean follow-up period was 46.97±21.87 months. The mean MBL change was significantly greater for SSRI users (0.41±0.76mm) compared to non-users (0.04±0.65mm) [MD=0.37mm, p=0.00, 95% CI: (-0.61)-(-0.15mm)]. Mesial MBL change of 0.42±0.84mm and 0.02±0.71mm was noted for SSRI users and non-users, respectively. The distal MBL change was 0.4±0.93mm and 0.07±0.73mm, respectively. Smoking, sex, and implant location did not seem to influence the MBL differences between groups. Use of SSRIs is associated with greater marginal bone loss around osseointegrated dental implants in function for a mean period of 3.8 years.

Selective serotonin reuptake inhibitor use and risk of major bleeding during treatment with vitamin K antagonists: results of a cohort study.

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding by decreasing platelet function or decreasing vitamin K antagonist (VKA) metabolism via cytochrome P450 (CYP) inhibition. To determine whether SSRIs are associated with major bleeding during VKA treatment and investigate the possible mechanisms. In this cohort study, information on SSRI use and bleeding complications was obtained from patient records of VKA initiators between 2006 and 2018 from two anticoagulation clinics. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRI users. The adjusted hazard ratio of major bleeding was 1.22 (95%CI 0.99-1.50) in all SSRI users and 1.31 (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRI users compared to non-users. SSRI use is associated with an increased risk of high INR and might be associated with major bleeding. The risk of a high INR was slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting there might be a pharmacokinetic interaction (by CYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation.

Risk of Gastrointestinal Bleeding with Concurrent Use of NSAID and SSRI: A Systematic Review and Network Meta-Analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used over-the-counter medications that can increase the risk of gastrointestinal (GI) bleeding through antiplatelet effects and loss of GI protection. Selective serotonin reuptake inhibitors (SSRIs), commonly used for mental and behavioral health, are another group of medications that can cause platelet dysfunction. Previous literature has shown a possible increased risk of GI bleeding with concurrent use of SSRIs and NSAIDs. We performed a network meta-analysis comparing NSAIDs, SSRIs, and combined SSRI/NSAIDs to assess the risk of GI bleeding. The following databases were searched: MEDLINE, Embase, Web of Science Core Collection, SciELO, KCI, and Cochrane database. All comparative studies, i.e., case-control, cohort, and randomized controlled trials were included. Direct and network meta-analysis was conducted using DerSimonian-Laird approach and random effect. For binary outcomes, odds ratio (OR) with 95% confidence interval (CI) and p value were calculated. After a comprehensive search through November 10th, 2021, 15 studies with 82,605 patients were identified. 11 studies reported higher rates of GI bleeds in SSRI/NSAID than SSRI users (36.9% vs 22.8%, OR 2.14, 95% CI 1.52-3.02, p < 0.001, I2 = 86.1%). 10 studies compared SSRI/NSAID to NSAID users with higher rates of bleeds in SSRI/NSAID group (40.9% vs 34.2%, OR 1.49, 95% CI 1.20-1.84, p < 0.001, I2 = 68.8%). The results were consistent using network meta-analysis as well. Given higher risk of bleeding with concurrent NSAIDs and SSRIs, prescribers should exercise caution when administering NSAIDs and SSRIs concurrently especially in patients with higher risks of GI bleeding.

Use of Selective Serotonin Reuptake Inhibitors Is Associated with a Lower Risk of Colorectal Cancer among People with Family History

Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical and population-based evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might play a role in preventing CRC. We performed a nationwide cohort study to explore whether the use of SSRIs could reduce CRC risk among individuals with family history. We identified individuals aged 50 and above who had one or more first-degree relatives diagnosed with CRC. A total of 38,617 incident SSRI users were identified and matched with 115,851 non-users, on a ratio of 1:3. The Cox regression model was used to calculate hazard ratios (HRs) and 95% CI confidence intervals (CIs). We found a significant negative association between SSRI use and the risk of CRC (adjusted HR, 0.77; 95% CI, 0.70-0.85). Restricted cubic spline regression showed a non-linear dose-responded relationship between SSRI use and CRC risk. The association was stronger in rectal cancer than colon cancer (adjusted HR, 0.73 vs. 0.79), and more pronounced in advanced-stage CRC than early-stage CRC (adjusted HR, 0.73 vs. 0.80). This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC.

Use of central nervous system drugs in combination with selective serotonin reuptake inhibitor treatment: A Bayesian screening study for risk of suicidal behavior.

Using other central nervous system (CNS) medications in combination with selective serotonin reuptake inhibitor (SSRI) treatment is common. Despite this, there is limited evidence on the impact on suicidal behavior of combining specific medications. We aim to provide evidence on signals for suicidal behavior risk when initiating CNS drugs during and outside of SSRI treatment. Using a linkage of Swedish national registers, we identified a national cohort of SSRI users aged 6-59 years residing in Sweden 2006-2013. We used a two-stage Bayesian Poisson model to estimate the incidence rate ratio (IRR) of suicidal behavior in periods up to 90 days before and after a CNS drug initiation during SSRI treatment, while accounting for multiple testing. For comparison, and to assess whether there were interactions between SSRIs and other CNS drugs, we also estimated the IRR of initiating the CNS drug without SSRI treatment. We identified 53 common CNS drugs initiated during SSRI treatment, dispensed to 262,721 individuals. We found 20 CNS drugs with statistically significant IRRs. Of these, two showed a greater risk of suicidal behavior after versus before initiating the CNS drug (alprazolam, IRR = 1.39; flunitrazepam, IRR = 1.83). We found several novel signals of drugs that were statistically significantly associated with a reduction in the suicidal behavior risk. We did not find evidence of harmful interactions between SSRIs and the selected CNS drugs. Several of the detected signals for reduced risk correspond to drugs where there is previous evidence of benefit for antidepressant augmentation (e.g., olanzapine, quetiapine, lithium, buspirone, and mirtazapine). Novel signals of reduced suicidal behavior risk, including for lamotrigine, valproic acid, risperidone, and melatonin, warrant further investigation.

Kidney function and prescribed dose in middle-aged and older patients starting selective serotonin reuptake inhibitors.

PurposeTo avoid adverse drug reactions, dose reductions are recommended when prescribing selective serotonin reuptake inhibitors (SSRIs) to patients with impaired kidney function. The extent of this practice in routine clinical care is however unknown. We aimed to evaluate the starting and maintenance SSRI doses prescribed to patients stratified by levels of kidney function in real‐world practice.MethodsUsing data from the Stockholm CREAtinine Measurements (SCREAM) project, we identified 101 409 new users of antidepressants (including 52 286 SSRI users) in the region of Stockholm during 2006–2019, who were ≥50 years of age and had a recent creatinine test taken in order to estimate glomerular filtration rate (eGFR). SSRI dose reduction was defined as a prescribed SSRI dose of ≤0.5 defined daily doses, according to current recommendations. We examined the associations between eGFR and reductions in initial dose and maintenance dose of SSRIs using logistic regression models.ResultsOverall, reductions in initial and maintenance dose were observed among 54.1% and 34.1% of new SSRI users. Nevertheless, about 40% of individuals with an eGFR <30 ml/min/1.73 m2 were prescribed an SSRI without dose reduction. After adjusting for age and other covariates, lower eGFR was associated with moderately higher odds of dose reduction, for both initial and maintenance dose. Compared to individuals with an eGFR of 90–104 ml/min/1.73 m2, the adjusted odds ratios for those with an eGFR <30 ml/min/1.73 m2 were 1.18 (95% CI: 1.03, 1.36) for initial dose reduction, and 1.49 (1.29, 1.72) for maintenance dose reduction. Stratified analyses showed stronger associations between lower eGFR and SSRI dose reduction among individuals aged 50–64 years and in those receiving prescriptions from psychiatric care.ConclusionsLower kidney function was moderately associated with a reduced SSRI dose, independently of age. Prescribing SSRIs to middle‐aged and older patients should not only consider patients' age but also their kidney function.