Alina Königsberg1, Susanne Sehner2, Sönke Arlt3, Bastian Cheng1, Claus Z Simonsen4, Florent Boutitie5, Joaquin Serena6, Vincent Thijs7,8, Martin Ebinger9,10, Matthias Endres9,11,12, Jochen B Fiebach9, Robin Lemmens13,14,15, Keith W Muir16, Norbert Nighoghossian17, Salvador Pedraza18, Christian Gerloff1, Götz Thomalla1. 1. Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. 2. Institut für Medizinische Biometrie und Epidemiologie, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. 3. Department of Psychiatry and Psychotherapy, Evangelical Hospital Alsterdorf, Hamburg, Germany. 4. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 5. Service de Biostatistique, Centre d'Investigation Clinique, Hospices Civils de Lyon, Lyon, France. 6. Department of Neurology, Hospital Universitario Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona, Spain. 7. Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia. 8. Department of Neurology, Austin Health, Heidelberg, Victoria, Australia. 9. Centrum für Schlaganfallforschung Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany. 10. Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany. 11. Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. 12. Exzellenz Cluster Neuro Cure, Charité-Universitätsmedizin Berlin, Berlin, Germany, DZHK, partner site Berlin, DZNE, partner site Berlin, Berlin, Germany. 13. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 14. Vesalius Research Center, VIB, Leuven, Belgium. 15. Experimental Neurology and Leuven Research Institute for Neurodegenerative Diseases (LIND), University of Leuven, Leuven, Belgium. 16. Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK. 17. Department of Neurology, Hospices Civils de Lyon, Lyon, France. 18. Department of Radiology, Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d'Investgació Biomèdica de Girona (IDIBGI), Girona, Spain.
Abstract
BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment withalteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.
RCT Entities:
BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute strokepatients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.