Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
06 2021
Historique:
revised: 20 02 2021
received: 14 01 2021
accepted: 22 02 2021
pubmed: 4 3 2021
medline: 13 8 2021
entrez: 3 3 2021
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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 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.

Identifiants

pubmed: 33657675
doi: 10.1111/ene.14797
doi:

Substances chimiques

Fibrinolytic Agents 0
Tissue Plasminogen Activator EC 3.4.21.68

Banques de données

ClinicalTrials.gov
['NCT01525290']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2017-2025

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Auteurs

Alina Königsberg (A)

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Susanne Sehner (S)

Institut für Medizinische Biometrie und Epidemiologie, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Sönke Arlt (S)

Department of Psychiatry and Psychotherapy, Evangelical Hospital Alsterdorf, Hamburg, Germany.

Bastian Cheng (B)

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Claus Z Simonsen (CZ)

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Florent Boutitie (F)

Service de Biostatistique, Centre d'Investigation Clinique, Hospices Civils de Lyon, Lyon, France.

Joaquin Serena (J)

Department of Neurology, Hospital Universitario Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona, Spain.

Vincent Thijs (V)

Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia.
Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.

Martin Ebinger (M)

Centrum für Schlaganfallforschung Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany.

Matthias Endres (M)

Centrum für Schlaganfallforschung Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Exzellenz Cluster Neuro Cure, Charité-Universitätsmedizin Berlin, Berlin, Germany, DZHK, partner site Berlin, DZNE, partner site Berlin, Berlin, Germany.

Jochen B Fiebach (JB)

Centrum für Schlaganfallforschung Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.

Robin Lemmens (R)

Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
Vesalius Research Center, VIB, Leuven, Belgium.
Experimental Neurology and Leuven Research Institute for Neurodegenerative Diseases (LIND), University of Leuven, Leuven, Belgium.

Keith W Muir (KW)

Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.

Norbert Nighoghossian (N)

Department of Neurology, Hospices Civils de Lyon, Lyon, France.

Salvador Pedraza (S)

Department of Radiology, Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d'Investgació Biomèdica de Girona (IDIBGI), Girona, Spain.

Christian Gerloff (C)

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Götz Thomalla (G)

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

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