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Selective serotonin reuptake inhibitor use in hip fracture patients: a Danish nationwide prevalence study.

ABSTRACT: Background and purpose - Selective serotonin reuptake inhibitors (SSRIs) are often used in the elderly and are associated with adverse effects. Therefore, it is important to ascertain the prevalence of SSRI use in fragile and surgery-treated hip fracture patients. Methods - This population-based prevalence study included Danish hip fracture patients aged ? 65 years operated in 2006-2016 (n = 68,607) and matched individuals from the background population (n = 343,020). Using Poisson regression, prevalence risk ratios (PRRs) with 95% confidence intervals (CIs) were estimated to compare hip fracture patients with the general population, and to estimate the association between hip fracture patient characteristics and SSRI prescriptions. Results - The prevalence of SSRI use among hip fracture patients was 23% compared with 12% in the general population. During 2006-2016, the prevalence decreased from 26% to 18% among hip fracture patients and from 13% to 10% in the general population. Factors associated with SSRI use in hip fracture patients were age 75-84 years (PRR 1.18, CI 1.13-1.23), age ? 85 years (PRR 1.17, CI 1.11-1.22), female sex (PRR 1.13, CI 1.09-1.17), unmarried status (PRR 1.15, CI 1.11-1.19), living in a residential institution (PRR 2.30, CI 2.19-2.40), Charlson comorbidity index (CCI) score 1-2 (PRR 1.50, CI 1.45-1.55), CCI score 3+ (PRR 1.62, CI 1.55-1.69), and several medications. Interpretation - The prevalence of SSRI use was high among hip fracture patients compared with the general population. Our data stress the importance of continued clinical awareness of frailty, comorbidity, and polypharmacy of hip fracture patients and the potentially adverse drug effects of SSRI treatment.

SUBMITTER: Bruun SB

PROVIDER: S-EPMC6366466 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Selective serotonin reuptake inhibitor use in hip fracture patients: a Danish nationwide prevalence study.

Bruun Stine B SB Petersen Irene I Kristensen Nickolaj R NR Cronin-Fenton Deirdre D Pedersen Alma B AB

Acta orthopaedica 20181210 1

Background and purpose - Selective serotonin reuptake inhibitors (SSRIs) are often used in the elderly and are associated with adverse effects. Therefore, it is important to ascertain the prevalence of SSRI use in fragile and surgery-treated hip fracture patients. Methods - This population-based prevalence study included Danish hip fracture patients aged ≥ 65 years operated in 2006-2016 (n = 68,607) and matched individuals from the background population (n = 343,020). Using Poisson regression, p ...[more]

PMID: 30526179

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Project description:PurposeTo examine the association between selective serotonin reuptake inhibitor (SSRI) use and mortality, postoperative complications, and quality of in-hospital care in hip fracture patients.Patients and methodsThe study was a nationwide cohort study based on individual-level linked, prospectively collected data from Danish population-based national registries covering all hospitals in Denmark. The health care system in Denmark is tax-funded, and all citizens have equal access to health care services. We included patients with first-time hospitalization due to hip fracture undergoing surgery from 2006-2016. We estimated the risk of 30-day mortality, any unplanned readmission, any reoperation, specific postoperative complications including cardiovascular events and major bleeding, and quality of in-hospital care using Cox and Poisson regression analyses comparing current and former SSRI users with non-users.ResultsIn 68,487 hip fracture patients, 13,272 (19%) were current SSRI users, 2,777 (4%) were former SSRI users, and 52,438 (77%) were SSRI non-users. The 30-day mortality risk was 13% in current SSRI users (HR 1.16, 1.10-1.21) and 12% in former (HR 1.15, 1.04-1.27) compared with 10% in non-users. The HR for any unplanned readmission was 1.11 (1.02-1.20) in current and 1.13 (1.01-1.27) in former SSRI users and for any reoperation 1.21 (1.11-1.31) in current and 1.04 (0.84-1.28) in former SSRI users compared with non-users. The risk of venous thromboembolism, myocardial infarction, stroke, and bleeding were similar irrespective of SSRI use. No association between current and former SSRI use and quality of in-hospital care was found.ConclusionIn patients undergoing hip fracture surgery, 30-day mortality and overall readmission risk were elevated in both current and former SSRI users compared with non-users. Those currently using SSRI had a 26% increased reoperation risk compared with non-users. However, SSRI use was not associated with increased risk of other postoperative complications and lower quality of in-hospital care. A limitation of this study was the inability to control for potential confounding of social deprivation.

Project description:Importance:In 2006, the US Food and Drug Administration (FDA) issued an advisory warning on the risk of serotonin syndrome with concomitant use of triptans and selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) antidepressants, but the true risk of serotonin syndrome in these patients remains unknown. Objective:To assess the risk of serotonin syndrome with concomitant use of triptans and SSRI or SNRI antidepressants. Design, Setting, and Participants:This study used electronic health record data from the Partners Research Data Registry (RPDR) to identify patients who had received an International Classification of Diseases, Ninth Revision diagnosis compatible with serotonin syndrome who had been coprescribed triptans and SSRI or SNRI antidepressants in the Greater Boston, Massachusetts, area from January 1, 2001, through December 31, 2014 (14 years). Clinical information was extracted to determine whether the case met formal diagnostic criteria and had coprescription within a calendar year. Both conservative and broad case definitions were used to better characterize the spectrum of risk. Data analysis was performed from November 23, 2016, to July 15, 2017. Main Outcomes and Measures:Incidence of serotonin syndrome. Results:The RPDR search revealed 47?968 (±3) unique patients who were prescribed triptans during the 14-year period of the study. A total of 19?017 (±3) patients were coprescribed triptans and antidepressants during the study, with a total of 30?928 person-years of exposure. Serotonin syndrome was suspected in 17 patients. Only 2 patients were classified as having definite serotonin syndrome (incidence rate, 0.6 cases per 10?000 person-years of exposure; 95% CI, 0.0-1.5). Five patients were classified as having possible serotonin syndrome (incidence rate with these 5 cases added to the 2 definite cases, 2.3 cases per 10?000 person-years of exposure; 95% CI, 0.6-3.9). The proportion of patients with triptan prescriptions who were coprescribed an SSRI or SNRI antidepressant was relatively stable during the study, ranging from 21% to 29%. Conclusions and Relevance:The risk of serotonin syndrome associated with concomitant use of triptans and SSRIs or SNRIs was low. Coprescription of these drugs is common and did not decrease after the 2006 FDA advisory. Our results cast doubt on the validity of the FDA advisory and suggest that it should be reconsidered.

Project description:ObjectiveTo examine the risk factors for new chronic opioid use in elderly patients who underwent hip fracture surgery.DesignProspective population-based cohort study.Setting and participantsUsing Danish nationwide health registries, we identified all opioid non-user patients aged ≥65 years who had undergone hip fracture surgery from 2005 to 2016 and were alive within the first year following surgery.Main outcome measuresNew chronic opioid use defined by the dispensing of at least two prescription opioids within two of the last three quarters during the first year following surgery.ResultsWe identified 37 202 opioid non-user patients who underwent hip fracture surgery. Of these, 5497 (15%) developed new chronic opioid user within 1 year of surgery. Risk factors for new chronic opioid use were Body Mass Index (BMI) of <18.5 (adjusted OR (aOR) 1.22, 95% CI 1.09 to 1.36), BMI of 25.0-29.9 (aOR 1.12, 95% CI 1.04 to 1.21) and BMI of ≥30 (aOR 1.57, 95% CI 1.40 to 1.76) with BMI 18.6-24.9 as reference, a pertrochanteric/subtrochanteric fracture (aOR 1.27, 95% CI 1.20 to 1.34) with femoral neck fracture as reference, preoperative use (vs no-use) of non-steroidal anti-inflammatory drug (aOR 1.68, 95% CI 1.55 to 1.83), selective serotonin reuptake inhibitor (aOR 1.42, 95% CI 1.32 to 1.53), antidepressants (aOR 1.36, 95% CI 1.24 to 1.49), antipsychotics (aOR 1.21, 95% CI 1.07 to 1.35), corticosteroids (aOR 1.54, 95% CI 1.35 to 1.76), statins (aOR 1.09, 95% CI 1.02 to 1.18), antibiotics (aOR 1.32, 95% CI 1.22 to 1.42), antiosteoporosis drugs (aOR 1.33, 95% CI 1.19 to 1.49) and anticoagulatives (aOR 1.24, 95% CI 1.17 to 1.32). Presence of cardiovascular comorbidities, diabetes, gastrointestinal diseases, dementia, chronic obstructive pulmonary disease or renal diseases was further identified as a risk factor.ConclusionIn this large nationwide cohort study, we identified several risk factors associated with new chronic opioid use after hip fracture surgery among patients who were alive within the first year following surgery. Although not all factors are modifiable preoperative, this will allow clinicians to appropriately counsel patients preoperatively and tailor postoperative treatment.

Project description:Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and μCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. © 2017 American Society for Bone and Mineral Research.

Project description:Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only one-half to two-thirds of MDD patients respond to SSRI therapy. Recently, a "multiple omics" research strategy was applied to identify genetic differences between patients who did and did not respond to SSRI therapy. As a first step, plasma metabolites were assayed using samples from the 803 patients in the PGRN-AMPS SSRI MDD trial. The metabolomics data were then used to "inform" genomics by performing a genome-wide association study (GWAS) for plasma concentrations of the metabolite most highly associated with clinical response, serotonin (5-HT). Two genome-wide or near genome-wide significant single nucleotide polymorphism (SNP) signals were identified, one that mapped near the TSPAN5 gene and another across the ERICH3 gene, both genes that are highly expressed in the brain. Knocking down TSPAN5 and ERICH3 resulted in decreased 5-HT concentrations in neuroblastoma cell culture media and decreased expression of enzymes involved in 5-HT biosynthesis and metabolism. Functional genomic studies demonstrated that ERICH3 was involved in clathrin-mediated vesicle formation and TSPAN5 was an ethanol-responsive gene that may be a marker for response to acamprosate pharmacotherapy of alcohol use disorder (AUD), a neuropsychiatric disorder highly co-morbid with MDD. In parallel studies, kynurenine was the plasma metabolite most highly associated with MDD symptom severity and application of a metabolomics-informed pharmacogenomics approach identified DEFB1 and AHR as genes associated with variation in plasma kynurenine levels. Both genes also contributed to kynurenine-related inflammatory pathways. Finally, a multiply replicated predictive algorithm for SSRI clinical response with a balanced predictive accuracy of 76% (compared with 56% for clinical data alone) was developed by including the SNPs in TSPAN5, ERICH3, DEFB1 and AHR. In summary, application of a multiple omics research strategy that used metabolomics to inform genomics, followed by functional genomic studies, identified novel genes that influenced monoamine biology and made it possible to develop a predictive algorithm for SSRI clinical outcomes in MDD. A similar pharmaco-omic research strategy might be broadly applicable for the study of other neuropsychiatric diseases and their drug therapy.

Dataset Information

Selective serotonin reuptake inhibitor use in hip fracture patients: a Danish nationwide prevalence study.

Publications

Selective serotonin reuptake inhibitor use in hip fracture patients: a Danish nationwide prevalence study.

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