Patrick C Souverein1, Victoria Abbing-Karahagopian1, Elisa Martin2, Consuelo Huerta2, Francisco de Abajo3,4, Hubert G M Leufkens1,5, Gianmario Candore6, Yolanda Alvarez6, Jim Slattery6, Montserrat Miret7, Gema Requena4, Miguel J Gil2, Rolf H H Groenwold1,8, Robert Reynolds9, Raymond G Schlienger10, John W Logie11, Mark C H de Groot1, Olaf H Klungel1,8, Tjeerd P van Staa1,12, Toine C G Egberts1,13, Marie L De Bruin1,4, Helga Gardarsdottir1,13. 1. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, The Netherlands. 2. BIFAP Research Unit, Division of Pharmacoepidemiology and Pharmacovigilance, Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Madrid, Spain. 3. Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Madrid, Spain. 4. Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Alcalá, Spain. 5. MEB, Medicines Evaluation Board, Utrecht, The Netherlands. 6. EMA, European Medicines Agency, London, United Kingdom. 7. Merck KGaA, Geneva, Switzerland. 8. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 9. Department of Epidemiology, Pfizer, New York, United States. 10. Global Clinical Epidemiology, Novartis Pharma AG, Basel, Switzerland. 11. Institute of Population Health, University of Manchester, Manchester, United Kingdom. 12. Worldwide Epidemiology, GlaxoSmithKline, Stockley Park, United Kingdom. 13. Department of Clinical Pharmacy, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract
PURPOSE: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs. METHODS: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture. A common protocol and statistical analysis plan was applied to harmonize study design and conduct between data sources. RESULTS: Current use of antidepressants was consistently associated with a 1.5 to 2.5-fold increased risk of hip/femur fractures in all data sources with both designs, with estimates for SSRIs generally higher than those for TCAs. In general, risk estimates in Mondriaan, the smallest data source, were higher compared to the other data sources. This difference may be partially explained by an interaction between SSRI and age in Mondriaan. Adjustment for GP-recorded lifestyle factors and matching on general practice had negligible impact on adjusted relative risk estimates. CONCLUSION: We found a consistent increased risk of hip/femur fracture with current use of antidepressants across different databases and different designs. Applying similar pharmacoepidemiological study methods resulted in similar risks for TCA use and some variation for SSRI use. Some of these differences may express real (or natural) variance in the exposure-outcome co-occurrences.
PURPOSE: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs. METHODS: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture. A common protocol and statistical analysis plan was applied to harmonize study design and conduct between data sources. RESULTS: Current use of antidepressants was consistently associated with a 1.5 to 2.5-fold increased risk of hip/femur fractures in all data sources with both designs, with estimates for SSRIs generally higher than those for TCAs. In general, risk estimates in Mondriaan, the smallest data source, were higher compared to the other data sources. This difference may be partially explained by an interaction between SSRI and age in Mondriaan. Adjustment for GP-recorded lifestyle factors and matching on general practice had negligible impact on adjusted relative risk estimates. CONCLUSION: We found a consistent increased risk of hip/femur fracture with current use of antidepressants across different databases and different designs. Applying similar pharmacoepidemiological study methods resulted in similar risks for TCA use and some variation for SSRI use. Some of these differences may express real (or natural) variance in the exposure-outcome co-occurrences.
Authors: Robyn Tamblyn; David W Bates; David L Buckeridge; William G Dixon; Nadyne Girard; Jennifer S Haas; Bettina Habib; Usman Iqbal; Jack Li; Therese Sheppard Journal: J Am Geriatr Soc Date: 2020-03-17 Impact factor: 5.562