Serotonin Reuptake Inhibitor Users Research Articles

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.

Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis

Background Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy. Methods We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results We did not identify any randomised studies but found 32 non-randomized studies (cohort or case–control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23–1.58; p < .001; moderate heterogeneity). Among individuals receiving antiplatelet therapy (2 studies), SRI users were associated with an increased risk of major bleeding: pooled OR was 1.45 (95% CI, 1.17–1.80; p = .001; low heterogeneity). For secondary outcomes, the use of SRI among individuals treated with antithrombotic therapy revealed a higher risk of gastrointestinal bleeding or any bleeding events, whereas only anticoagulant use was illustrated an increased risk of intracranial haemorrhage. Conclusions The use of SRI antidepressants among patients treated with antithrombotic therapy (either anticoagulant or antiplatelet) is associated with a higher risk of bleeding complications, suggesting that caution is warranted in co-prescription. PROSPERO Registration CRD42018083917 KEY MESSAGES In this meta-analysis of 32 non-randomized studies, SRI users were associated with the risk of bleeding complications compared to non-SRI users, with concurrent antithrombotic use (either anticoagulant or antiplatelet). The risk was consistently elevated across types of bleeding events (major bleeding, gastrointestinal bleeding, or any bleeding events), whereas only anticoagulant use was associated with intracranial haemorrhage. To promote the rational use of medicines, our findings suggest that the risk-benefit ratio must account for the clear efficacy of SRI against safety concerns in terms of bleeding risks.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Potentially Inappropriate Drug Duplication in a Cohort of Older Adults with Dementia

BackgroundConcurrent use of 2 nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, loop diuretics, angiotensin-converting enzyme inhibitors, or anticoagulants is considered potentially inappropriate by Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment criteria.ObjectiveThe objective was to examine drug duplication in a cohort of older adults with dementia.MethodsCohort entry for Nova Scotia Seniors’ Pharmacare Program beneficiaries was the date an International Classification of Diseases ninth edition or 10th edition code for dementia was recorded in accessed databases between March 1, 2005, and March 31, 2015. Medication dispensation and sociodemographic data were captured from the Nova Scotia Seniors’ Pharmacare Program database between April 1, 2010, and March 31, 2015. Duplication was considered when 2 drugs from the same class were dispensed such that the supply in the patient's possession could overlap for more than 30 days. We reported number of cases of duplication and duration of overlap. Sex differences in drug duplication were assessed with bivariate logistic regression.ResultsIn the cohort of 28,953 Nova Scotia Seniors’ Pharmacare Program beneficiaries with dementia, we documented concurrent use in 101 (1.7%) nonsteroidal anti-inflammatory drugs users (mean duration = 75.6 days), 95 (1.0%) selective serotonin reuptake inhibitors users (mean duration = 146.6 days), 5 (0.07%) loop diuretic users (mean duration = 530.6 days), 183 (2.0%) angiotensin-converting enzyme inhibitor users (mean duration = 123.9 days), and 160 (3.5%) anticoagulant users (mean duration = 63.6 days). Nonsteroidal anti-inflammatory drug pairs were most commonly celecoxib with naproxen or diclofenac. Selective serotonin reuptake inhibitors duplication was most commonly sertraline with citalopram. No sex differences in risk for drug duplication were identified.ConclusionsDrug duplication was identified in a cohort of older adults with dementia and is a feasible target for intervention. (Curr Ther Res Clin Exp. 2021; 82:XXX–XXX)

Association Between Cerebral Small Vessel Disease With Antidepressant Use and Depression: 3C Dijon Magnetic Resonance Imaging Study.

Background and Purpose- Evidence links antidepressant use with cerebral small vessel disease; however, it remains unclear whether people with depression face comparable risk. This study aims to determine the association between antidepressant drug use and depression with markers of cerebral small vessel disease. Methods- One thousand nine hundred five participants (mean age, 72.5 years; 60% women) without stroke or dementia history underwent brain magnetic resonance imaging at baseline, and 1402 individuals underwent a second magnetic resonance imaging at 4 years. Outcomes were lacunes 3 to 15 mm and white matter hyperintensity volume (cm3) at baseline and follow-up. Exposure to antidepressants was grouped as (1) selective serotonin reuptake inhibitors (n=68), (2) tricyclics (n=40), (3) atypicals (n=24), (4) depressed nonusers (n=303), and (5) nondepressed/nonuser group (reference group, n=1470). Statistical analyses adjusted for propensity scores due to the nonrandomized exposure to antidepressant drugs. Results- There was an association between use of atypical antidepressants with lacunes at baseline (adjusted rate ratio, 2.59 [95% CI, 1.14-5.88]; P=0.023) and follow-up (adjusted rate ratio, 3.05 [95% CI, 1.25-7.43]; P=0.014). Lacunes at baseline were also associated with depressed nonusers (adjusted rate ratio, 1.53 [95% CI, 1.06-2.21]; P=0.023). Selective serotonin reuptake inhibitor users and depressed nonusers displayed higher total, periventricular, and deep white matter hyperintensity volumes at baseline. Selective serotonin reuptake inhibitor users had higher deep white matter hyperintensity volumes at follow-up. Conclusions- Users of atypical antidepressants, selective serotonin reuptake inhibitors, and depressed people without any antidepressant exposure all displayed markers of cerebral small vessel disease higher than the nondepressed/nonuser group. The findings suggest that cerebral small vessel disease is associated with depression and exposure to antidepressants.

Evaluation of jawbonemorphology and bonedensityindices in panoramic radiographs of selectiveserotoninreuptakeinhibitorusers: a preliminary study.

To assess the influence of selective serotonin reuptake inhibitor (SSRI) use on jawbone and bone mineral density by retrospective analysis of panoramic radiographs. Radiographic and clinical records were sourced from the Division of Orthodontics and TMJD, Eastman Institute for Oral Health, University of Rochester. Randomly selected adults (20-65 years) were categorized into: "Active" (with history of SSRI use of >6 months) and a "Control" group. Panoramic indices: Klemetti index (KI), panoramic mandibular index, antegonial notching index, condylar pathology, mandibular cortical width (MCW)⁠ and mean ramus height were recorded. Frequency-weighted Χ2 tests and multinomial regression controlling for age and gender were applied to categorical indices (KI, condylar pathology, antegonial notching index). Multivariate generalized linear modeling was applied to mean ramus height, MCW and panoramic mandibular index. Multiple regression analyses determined: (a) panoramic indices that best predicted SSRI use, and (b) independent predictors of KI category. 64 SSRI users and 48 Controls were assessed. SSRI users had significantly higher odds of having worse KI status than normal [mildly to moderately eroded cortex: odds ratio (OR) = 2.926, 95% CI (1.07-8.04) and severely eroded cortex: OR = 19.86, 95% CI (3.91-100.69)], more frequent flat condylar anatomy (right side: p = 0.009, left side: p < 0.001) but greater ramus height (p = 0.001) and mandibular cortical width (p = 0.032). Age, gender, SSRI use each significantly impacted KI. Only SSRI use significantly impacted condylar pathology, ramus height and MCW. KI category (OR = 1.3) was the best panoramic predictor of SSRI use. Conversely, KI category C3 was significantly predicted by SSRI use (OR = 31.2, p = 0.002), female gender (17.5, p = 0.006), and severe antegonial notching (OR = 1289, p < 0.001). SRRI use was significantly associated with worse panoramic morphometric indices: KI, condylar pathology, ramus height, and MCW, where KI was its strongest predictor. Worse KI was independently predicted by SSRI use.

Clinical Management of Bleeding Risk With Antidepressants.

This nonsystematic review describes risk of bleeding in treatment with serotonin reuptake inhibitors (SRIs) and provide recommendations for the management of patients at risk of bleeding. Articles were identified by English-language MEDLINE search published prior to June 2018 using the terms SRI, serotonin and noradrenaline reuptake inhibitors, OR antidepressive agents, AND hemorrhage OR stroke. Meta-analyses were utilized to identify information regarding risk of bleeding with antidepressants. Individual studies were included if they had information regarding bleeding risk with specific SRIs, timing of risk, or risk with medications of interest. SRIs increase risk of bleeding by 1.16- to 2.36-fold. The risk is synergistic between SRIs and nonsteroidal anti-inflammatory drugs (NSAIDs; odds ratio [OR] range between studies 3.17-10.9). Acid-reducing medications may mitigate risk of gastrointestinal bleeds in chronic NSAIDs and SRI users (OR range between studies 0.98-1.1). Antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be appropriate alternatives for patients at risk of bleeding. Relevance to Patient Care and Clinical Practice: This review includes data regarding bleeding risk for specific antidepressants, concomitant medications, and risk related to duration of SRI use. Considerations and evidence-based recommendations are provided for management of SRI users at high bleeding risk. Clinicians must be aware of the risk of bleeding with SRI use, especially for patients taking NSAIDs. Patient education is prudent for those prescribed NSAIDs and SRIs concurrently.

Antidepressant use and cognitive decline in community-dwelling elderly people \u2013 The Three-City Cohort

BackgroundCognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period.MethodsThe community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale.ResultsAt baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users.ConclusionsIn this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various cognitive domains.

Cardiac Toxicity in Selective Serotonin Reuptake Inhibitor Users.

Several classes of recreational and prescription drugs have been associated with an increased risk of cardiovascular disease and the occurrence of arrhythmias, which may be involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart, which may be caused by selective serotonin reuptake inhibitor use and their possible role in the occurrence of sudden cardiac death. A total of 40 cases were included in the study and were divided evenly into 2 groups: 20 cases of patients treated with selective serotonin reuptake inhibitors and 20 cases of sudden deaths involving patients void of any drug treatment. The first group included 16 patients treated with citalopram and 4 with sertraline. Autopsies, histology, biochemistry, and toxicology were performed in all cases. Pathological changes in selective serotonin reuptake inhibitor users consisted of various degrees of interstitial and perivascular fibrosis as well as a small degree of perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, the results of this study seem to confirm former observations on this topic, suggesting that selective serotonin reuptake inhibitors may play a potential, causative role in the pathogenesis of sudden deaths in chronic users even at therapeutic concentrations.

Use of Antidepressants Near Delivery and Risk of Postpartum Hemorrhage

Objective To determine whether use of serotonin or non-serotonin reuptake inhibitors near to delivery is associated with postpartum hemorrhage. Design Cohort study. Setting 2000-07 nationwide Medicaid data (Medicaid Analytic eXtract). Population 106 000 pregnant women aged 12-55 with a diagnosis of mood or anxiety disorder. Women were categorized into four mutually exclusive exposure groups according to pharmacy dispensing data: current (delivery date), recent (1-30 days before delivery date), past (1-5 months before delivery date), and no exposure (reference group). Main outcome measures Risk of postpartum hemorrhage by timing of exposure and by serotonin or non-serotonin reuptake inhibitors, classes of antidepressant, and antidepressant types. Relative risks and 95% confidence intervals adjusted for delivery year, risk factors for postpartum hemorrhage, indicators of severity of mood/anxiety disorder, other indications for antidepressants, and other drugs. High dimensional propensity score (hdPS) methods were used to empirically identify and adjust for additional factors. Results 12 710 (12%) women had current exposure to serotonin reuptake inhibitor monotherapy, and 1495 (1.4%) women had current exposure to non-serotonin reuptake inhibitor monotherapy. The risk of postpartum hemorrhage was 2.8% among women with mood/anxiety disorders but no exposure to antidepressants, 4.0% in the current users of serotonin reuptake inhibitors, 3.8% in the current users of non-serotonin reuptake inhibitors, 3.2% in the recent users of serotonin reuptake inhibitors, 3.1% in the recent users of non-serotonin reuptake inhibitors, 2.5% in the past users of serotonin reuptake inhibitors, and 3.4% in the past users of non-serotonin reuptake inhibitors. Compared with no exposure, women with current exposure to serotonin reuptake inhibitors had a 1.47-fold increased risk of postpartum hemorrhage (95% confidence interval 1.33 to 1.62) and women with current non-serotonin reuptake inhibitor exposure had a 1.39-fold increased risk (1.07 to 1.81). Results were similar with hdPS adjustment. Women with current exposure to serotonin reuptake inhibitors had an adjusted excess risk of 1.26% (0.90% to 1.62%), with a number needed to harm of 80, and for women with current exposure to non-serotonin reuptake inhibitors the excess risk was 1.03% (0.07% to 1.99%), with a number needed to harm of 97. For exposure to serotonin reuptake inhibitors the relative risk was 1.19 (1.03 to 1.38) for recent exposure and 0.93 (0.82 to 1.06) for past exposure; for non-serotonin reuptake inhibitors the figures were 1.17 (0.80 to 1.70) and 1.26 (1.00 to 1.59), respectively. Current exposure to selective serotonin reuptake inhibitor monotherapy was also associated with postpartum hemorrhage (1.42, 1.27 to 1.57), as was current serotonin norepinephrine (noradrenaline) reuptake inhibitor (1.90, 1.37 to 2.63) and tricyclic monotherapy (1.77, 0.90 to 3.47). All types of selective serotonin reuptake inhibitors available for analysis and venlafaxine, a serotonin norepinephrine reuptake inhibitor, were significantly associated with postpartum hemorrhage. Conclusions Exposure to serotonin and non-serotonin reuptake inhibitors, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclics, close to the time of delivery was associated with a 1.4 to 1.9-fold increased risk for postpartum hemorrhage. While potential confounding by unmeasured factors cannot be ruled out, these findings suggest that patients treated with antidepressants during late pregnancy are more likely to experience postpartum hemorrhage.

Selective Serotonin Reuptake Inhibitor Use and Increased Risk of Cataract Surgery: A Population-Based, Case-Control Study

To investigate whether selective serotonin reuptake inhibitor use is associated with an increased risk of cataract surgery. Population-based case-control study. setting: Olmsted County, Minnesota. patient population: Eligible patients were county residents in the Rochester Epidemiology Project. Cases included 6024 county residents aged 50+ years who underwent first-eye cataract surgery between January 1, 2004 and December 31, 2011. Controls included 6024 residents who never had cataract surgery and were matched to cases by age, sex, and date of surgery. Logistic regression models were used to compute odds ratios for differences in selective serotonin reuptake inhibitor use between cases and controls, and to adjust for confounding variables. observation procedure: Rochester Epidemiology Project databases were used to assess cataract surgery and selective serotonin reuptake inhibitor treatment. main outcome measure: Selective serotonin reuptake inhibitor use. In the cataract surgery cohort of 6024 residents, 1024 (17%) were selective serotonin reuptake inhibitor users compared to 788 (13%) in the matched cohort of 6024 residents never having cataract surgery (P < .001). Selective serotonin reuptake inhibitor use of 1 or more years was associated with an increased risk of cataract surgery (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.23-1.51; P < .001). The associations were similar in women (OR = 1.37; 95% CI, 1.22-1.55; P < .001) and men (OR = 1.34; 95% CI, 1.12-1.61; P = .002). The risk of cataract surgery was highest with citalopram use (OR = 1.53; 95% CI, 1.33-1.77; P < .001). Selective serotonin reuptake inhibitor use of 1 or more years in people aged 50+ years is associated with an increased risk of cataract surgery.

Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States

Objective To determine whether use of serotonin or non-serotonin reuptake inhibitors near to delivery is associated with postpartum hemorrhage. Design Cohort study. Setting 2000-07 nationwide Medicaid data (Medicaid Analytic eXtract)....

Reports of Sexual Disorders Related to Serotonin Reuptake Inhibitors in the French Pharmacovigilance Database: An Example of Underreporting

Depressive disorders and use of antidepressants are associated with adverse effects on sexual function. In pharmacoepidemiological studies, sexual disorders are reported by more than 50% of patients taking serotonin reuptake inhibitors (SRIs). The aim of this study was to determine the reporting rate of sexual disorders in association with SRIs, and to investigate the association between reported cases and the use of SRIs. All cases of adverse drug reactions (ADRs) involving sexual disorders, spontaneously reported to the French Pharmacovigilance Database from 1 January 1985 to December 2009, were reviewed. Cases of sexual disorders in SRI users were described. We calculated the rate of reported sexual disorders as a percentage of the total ADRs reported for each drug. The association between reported cases and the use of SRIs was assessed using reporting odds ratios (ROR) with 95% confidence intervals (CIs). A total of 11,863 ADRs in association with SRIs were collected, of which 98 (0.83%) were spontaneous reports of sexual disorders. Subjects were, on average, 45.0±10.6 years of age and mainly male. Sexual disorders were associated with the use of SRI antidepressants (ROR 4.47; 95% CI 3.61-5.53), milnacipran (ROR 11.72; 95% CI 5.79-23.72), fluvoxamine (ROR 6.91; 95% CI 3.79-12.58), paroxetine (ROR 5.54; 95% CI 3.92-7.83), venlafaxine (ROR 3.50; 95% CI 1.93-6.36), fluoxetine (ROR 3.46; 95% CI 2.26-5.29), citalopram (ROR 2.69; 95% CI 1.28-5.67) and sertraline (ROR 2.49; 95% CI 1.03-6.01). It is likely that there are instances of underreporting, particularly for ADRs that are embarrassing to talk about spontaneously. Despite the likely underreporting of this well-described adverse effect, this case/non-case study performed in a large national pharmacovigilance database confirms the existence of the risk of sexual disorders associated with SRIs, and is an example of the lack of sensitivity of spontaneous notification to measure ADRs. Minimization of antidepressant-induced sexual dysfunction could be an important factor to avoid unsuccessful treatment. Physicians should advise their patients on the possible sexual adverse effects.

Antidepressants and Bleeding Risk After Face-lift Surgery

To determine the rate of post-face-lift hematoma among users of serotonin reuptake inhibitors (SSRIs) vs non-SSRI users. Selective serotonin reuptake inhibitors have come under recent scrutiny because of possible bleeding risks. However, cessation of SSRIs carries inherent risks. The medical charts for 250 consecutive patients who underwent a modified deep-plane face-lift and 13 patients who underwent neck-lift from January 2010 to May 2011 were reviewed for the incidence of postoperative hematoma. Patients' medical records were examined for medical comorbidities, coagulopathy, and medication list, with particular attention to any usage of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs). Twenty-two percent of patients were taking SSRIs or SNRIs. We observed a total hematoma (major + minor) rate of 1.95% for non-SSRI/SNRI users vs 1.72% for SSRI/SNRI users. The minor hematoma rate was 1.95% among nonusers vs 0% for users. The major hematoma rate was 0% among nonusers vs 1.72% for users. Usage of SSRIs was more common in this large series of face-lift patients than in the general population. In these patients, SSRIs in the perioperative period are found to be safe and did not seem to adversely affect outcome. We found no evidence to support discontinuing SSRIs perioperatively.

Serotonin Reuptake Inhibitors and Hyperprolactinaemia

Hyperprolactinaemia is a common endocrinological disorder that can be caused by a variety of physiological and pathological conditions, although in a large proportion of cases hyperprolactinaemia is drug-induced. Serotonin reuptake inhibitors (SRIs) are reportedly associated with hyperprolactinaemia; however, the number of published cases in the literature is limited. The aim of the study was to investigate the association between exposure to SRIs and the risk of reporting of hyperprolactinaemia in a spontaneous reporting database. All cases of adverse drug reactions (ADRs) involving hyperprolactinaemia spontaneously reported to the French Pharmacovigilance Database from 1985 to December 2009 were reviewed. Cases of hyperprolactinaemia in SRI users were described. In a case/non-case analysis, the association between reported cases of hyperprolactinaemia and the use of SRIs was assessed by calculating reporting odds ratios (ROR) with their 95% confidence intervals (CIs). A total of 11 863 reports with SRIs were collected, of which 187 reported hyperprolactinaemia ADRs. Subjects were 39.7 ± 13.5 years of age on average and mainly female (71%). We observed an increased risk of reporting of hyperprolactinaemia with the use of SRIs as antidepressants (overall ROR 3.3; 95% CI 2.8, 3.8), particularly with fluvoxamine (ROR 4.5; 95% CI 2.8, 7.2), citalopram (ROR 3.9; 95% CI 2.6, 5.8), fluoxetine (ROR 3.6; 95% CI 2.8, 4.7) and paroxetine (ROR 3.1; 95% CI 2.3, 4.2). Duloxetine, milnacipran and sertraline were not associated with an increased risk of reporting of hyperprolactinaemia. Treatment with SRIs is associated with an increased risk of reported hyperprolactinaemia. When investigating the aetiology of diagnosed hyperprolactinaemia, physicians should systematically enquire about treatment with SRIs. The risk of hyperprolactinaemia should be mentioned in the labelling of all SRI compounds.

Concomitant Use of Gastroprotective Drugs among Elderly NSAID/COX-2 Selective Inhibitor Users

NSAIDs and cyclo-oxgenase (COX)-2-selective inhibitors have been associated with gastrointestinal (GI) complications among the elderly. It is recommended that gastroprotective drugs (i.e. misoprostol, proton pump inhibitors or high doses of histamine H2 receptor antagonists) be taken concomitantly to prevent NSAID-induced GI complications among older people. However, there are concerns that the rate of concomitant use of gastroprotective drugs in elderly NSAID users is too low. This study aimed to investigate the extent to which elderly users of NSAIDs/COX-2-selective inhibitors are concurrently taking gastroprotective drugs, and to determine the factors associated with concomitant use of gastroprotective drugs and NSAIDs/COX-2-selective inhibitors in a nationwide population of older people. We analysed data on age, sex and dispensed drugs for people>or=75 years of age registered in the Swedish Prescribed Drug Register from October to December 2005 (n=732,230) and located 41,626 NSAID/COX-2-selective inhibitor users. Logistic regression analysis was used for analysing the association between the use of different NSAIDs/COX-2-selective inhibitors and gastroprotective drugs, and between individual characteristics and use of gastroprotective drugs. Gastroprotective drugs were used by 22% of NSAID/COX-2-selective inhibitor users. Celecoxib, ketoprofen, meloxicam and etoricoxib were most commonly used concomitantly with gastroprotective drugs. Meloxicam and celecoxib were most strongly associated with gastroprotective drugs, after adjustment for age, sex and number of other drugs. Furthermore, NSAID/COX-2-selective inhibitor+oral corticosteroid users, NSAID/COX-2-selective inhibitor+selective serotonin reuptake inhibitor users and users of two or more NSAIDs/COX-2-selective inhibitors were more likely to concomitantly use gastroprotective drugs compared with NSAID/COX-2-selective inhibitor only users, after adjustment for age, sex and number of other drugs. However, users of NSAIDs/COX-2-selective inhibitors+anticoagulants (both warfarin and low-dose aspirin [acetylsalicylic acid]) did not show an increased likelihood of concomitant use of gastroprotective drugs, after adjustment for age, sex and number of other drugs. Our results indicate that gastroprotective drugs are not prescribed to elderly NSAID users according to guidelines. Furthermore, COX-2-selective inhibitors were used with gastroprotective drugs more often than were traditional NSAIDs. Greater awareness of factors contributing to NSAID/COX-2-selective inhibitor-induced GI complications is warranted, particularly with respect to advanced age and concurrent use of anticoagulants.

Effect of Selective Serotonin-Reuptake Inhibitors on the Risk of Fracture

Evaluation of: Richards JB, Papaioannou A, Adachi JD et al.: Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch. Intern. Med. 167, 188–194 (2007) [1] . The results of a cohort study of 5008 community-dwelling subjects aged over 50 years was presented. Among these, 137 were daily users of selective serotonin-reuptake inhibitors. The study reported an increased risk of fragility fractures (fractures occurring after minimal trauma; hazard ratio: 2.1; 95% confidence interval: 1.3–3.4) and an increased risk of falls (hazard ratio: 2.2; 95% confidence interval: 1.4–3.5) among daily users of selective serotonin-reuptake inhibitors. Bone mineral density was lower in the hip in daily selective serotonin-reuptake inhibitors users and there was a trend towards lower bone mineral density in the spine. A dose–response relationship was present.

The Role of Cohort Studies in Drug Development: Clinical Evidence of Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA Reductase Inhibitors in the Central Nervous System

Effective antiretroviral therapy (ART) has reduced the incidence of HIV-associated neurocognitive impairment (HNCI) but its prevalence remains high. Clinical trials have yet to identify a consistently effective treatment for HNCI, other than ART, but in vitro data support that some drugs approved by the Food and Drug Administration (FDA) for other indications might benefit individuals with HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in the CNS and are already widely used by HIV-infected individuals. Six-hundred fifty-eight HIV-infected participants of the CHARTER cohort had a baseline assessment, which included comprehensive neuropsychological (NP) testing and HIV RNA measurements in plasma and cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used ART, 195 (30%) used SRIs, and 63 (10%) used statins. SRI users were less likely to have HIV RNA levels in CSF above 50 copies (c)/mL (29 vs. 37% in non-SRI users, OR 0.69, p = 0.05). This association was most evident for three of the seven SRIs (citalopram, sertraline, and trazodone, or "antiviral" SRIs, combined 25 vs. 38% in non-SRI users, OR 0.56, p = 0.01) and was strongest in those not taking concomitant ART (61 vs. 83%, OR 0.31, p = 0.01). "Antiviral" SRI users also performed better on NP tests (median global deficit score 0.37 vs. 0.47, p = 0.04). Statin users were also less likely to have HIV RNA levels in CSF above 50 c/mL (16 vs. 37%, p < 0.001) but, in contrast to SRIs, the association was strongest in those taking ART (2 vs. 18%, p < 0.001). Statin use was not associated with better NP performance. Multivariate analyses indicated that the use of "antiviral" SRIs-but not statins-was associated with undetectable HIV RNA levels in CSF and better NP performance. SRIs may reduce HIV replication in CSF and improve NP performance. This was particularly true for three SRIs-supporting differences in antiviral efficacy between drugs-in individuals who were not taking ART. In contrast, statins were not associated with lower HIV replication in CSF in multivariate analyses and were not associated with better NP performance. These analyses support the value of large observational cohort studies in identifying FDA-approved drugs that may be worth further investigation.

Concomitant prescribing of benzodiazepines during antidepressant therapy in the elderly

A follow-up study was performed in two ambulatory cohorts aged ⩾65 to investigate whether the prevalence and incidence of anxiolytic/hypnotic benzodiazepine drug prescribing is comparable between users of serotonin reuptake inhibitors (SSRIs) and users of tricyclic antidepressants (TCAs). The prevalence and incidence of benzodiazepines during antidepressant therapy was estimated among users of TCAs and SSRIs. Coprescribing of benzodiazepines occurred in 53% of the TCA users and 57% of the SSRI users (prevalence RR 1.1; CI 95 0.9–1.2). The average duration of benzodiazepine drug use was >65 days per 100 days of antidepressant use. During SSRI therapy, significantly more people started benzodiazepine drug therapy than during TCA therapy (incidence rate ratio (RR) 1.7; CI 95 1.2–2.4). Analyses repeated 5 years later yielded similar results (overall incidence RR MH 1.6; CI 95 1.3–2.0). These data indicate that SSRI use is associated with a significantly higher chance of starting benzodiazepines compared with TCA use.