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Effect of intravenous alteplase on post‐stroke depression in the WAKE UP trial
Author(s) -
Königsberg Alina,
Sehner Susanne,
Arlt Sönke,
Cheng Bastian,
Simonsen Claus Z.,
Boutitie Florent,
Serena Joaquin,
Thijs Vincent,
Ebinger Martin,
Endres Matthias,
Fiebach Jochen B.,
Lemmens Robin,
Muir Keith W.,
Nighoghossian Norbert,
Pedraza Salvador,
Gerloff Christian,
Thomalla Götz
Publication year - 2021
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.14797
Subject(s) - medicine , modified rankin scale , stroke (engine) , depression (economics) , placebo , odds ratio , thrombolysis , confidence interval , post stroke depression , randomized controlled trial , physical therapy , anesthesia , treatment and control groups , myocardial infarction , ischemic stroke , mechanical engineering , alternative medicine , ischemia , pathology , engineering , economics , macroeconomics
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.