Background and Purpose— Recent studies indicate a possible beneficial effect on neuroregeneration and vascular protection of selective serotonin reuptake inhibitors after stroke. We conducted a national multicentre study to explore these effects. Methods— The TALOS study (The Efficacy of Citalopram Treatment in Acute Stroke) is a Danish placebo-controlled, randomized, double-blind study of citalopram started within 7 days after symptom onset to detect improvement in functional outcomes and cardiovascular protection in nondepressed, first-ever ischemic stroke. Study medication was given as add-on to standard medical care and treatment duration and follow-up was 6 months. There were 2 coprimary outcomes: changes in functional disability from 1 to 6 months on the modified Rankin Scale, and a composite vascular end point of transient ischemic attack/stroke, myocardial infarction, or vascular mortality during the first 6 months. Results— We enrolled 642 patients randomized to either citalopram (n=319) or placebo (n=323). Median National Institutes of Health Stroke Scale was 5.3 (range, 0–27) versus 4.8 (range, 0–28) at admission. Improvement in functional recovery from 1 to 6 months occurred in 160 (50%) patients on citalopram and 136 (42%) on placebo (odds ratio, 1.27; 95% CI, 0.92–1.74; P =0.057). When dropouts before 31 days were excluded (n=90), the analysis population showed an odds ratio of 1.37 (95% CI, 0.97–1.91; P =0.07). During a median follow-up of 150 days, 23 (7%) patients in the citalopram group and 26 (8%) patients in the placebo group had a primary, vascular end point (hazard ratio, 0.89; 95% CI, 0.50–1.60; P =0.24). A total of 28 patients (4%) died (16 versus 12; P =0.42) during the study. Conclusions— Early citalopram treatment did not improve functional recovery in nondepressed ischemic stroke patients within the first 6 months, although a borderline statistical significant effect was observed in the analysis population. The risk of cardiovascular events was similar between treatment groups, and citalopram treatment was well tolerated. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01937182. URL: https://www.clinicaltrialsregister.eu/ . EudraCT number: 2013-002253-30.

<b><i>Introduction:</i></b> Physical activity (PA) is associated with a lower risk of stroke and stroke mortality as well as a favorable stroke outcome. PA may also prevent general cognitive decline. Poststroke cognitive impairment is both common and disabling, and focusing on all possible preventive measures is important. Studies on the effect of PA on poststroke cognitive performance are sparse, however. We therefore aimed to examine the association between prestroke PA and poststroke cognitive performance. <b><i>Methods:</i></b> We studied the correlation between prestroke PA and poststroke cognitive performance in a prespecified analysis in The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial. We used the Physical Activity Scale for the Elderly (PASE) to collect information on PA during the 7-day period before stroke. PA was quantified, and patients were stratified into quartiles based on their PASE score. Cognitive performance was measured using the Symbol Digit Modalities Test (SDMT) at 1 and 6 months and the Mini-Mental State Examination (MMSE) at 6 months. The functional outcome was assessed using the modified Rankin Scale (mRS). <b><i>Results:</i></b> In total, 625 of 642 patients (97%) completed the PASE questionnaire. The median age was 69 (interquartile range [IQR]: 60–77), and the median PASE score was 137 (82–205). Higher prestroke PASE quartiles (2nd, 3rd, and 4th, each compared to the 1st) were independently associated with a higher SDMT score at 1 month in the both the univariable and multivariable analyses (2nd: 3.99 points, 95% confidence interval [CI]: 1.01–6.97; 3rd: 3.6, CI: 0.6–6.61; 4th: 4.1, CI: 0.95–7.24). This association remained at 6 months. PA was not statistically associated with the MMSE score or mRS. <b><i>Conclusion:</i></b> Higher prestroke PA was associated with a better cognitive performance as measured by the SDMT at 1 and 6 months poststroke. We found no significant association between prestroke PA and functional outcome. Our results are encouraging and support further investigations of PA as a protective measure against poststroke cognitive impairment.