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

Background To study the effect of intravenous alteplase on 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 endpoint of PSD was defined as a Beck Depression Inventory BDI ≥10, medication with an antidepressant, or depression recorded as an adverse event. We used multiple logistic regression 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 (mRS). Results Information on the composite endpoint 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 (OR 0.63; 95% CI 0.43-0.94; p=0.022; adjusted for age and National Institutes of Health Stroke Scale [NIHSS] 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 was caused directly, while 35% where 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 was only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk PSD.