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Background: Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits.Methods: Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months.Results: During the study period (03/2017–12/2018), 114 patients were assigned to sertraline (n = 72, 62.6%) or control group (n = 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 [IQR, 5–11] vs. 5 [IQR, 4–7]; p = 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 [IQR 2–7] vs. 2 [IQR 2–4], p = 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02–9.41; p = 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 [49.1%] vs. 14/28 [50.0%] patients, p = 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 [0%] vs. 5/28 [17.9%] patients, p = 0.004).Conclusions: In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.

BackgroundThe impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population.MethodsWe searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran’s Q test and I2 statistics.ResultsWe included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16–2.05, p < 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97–4.31; p = 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15–3.59, p < 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51–0.86, p < 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14–2.91, p = 0.56).ConclusionCOVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome.Systematic review registrationhttps://clinicaltrials.gov/, identifier CRD42022309785.

Introduction: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, citalopram and escitalopram have been suggested to improve functional recovery after acute ischemic stroke (AIS) due to modulation of autonomic cardiovascular and inflammatory pathways independently of changes in depressivity. Although sertraline has shown highest degree of tolerability and efficacy among SSRIs in the treatment of depression, its effects on functional recovery from AIS remain unknown. Hypothesis: We hypothesized that sertraline is associated with improved functional recovery from AIS which is paralleled by alleviation of autonomic symptoms and depressivity. Methods: We analyzed data of an ongoing prospective observational study in AIS patients who were admitted to our stroke center from 03/2017 to 08/2018 and had no disability pre-stroke (mRS 0-1). Patients who received sertraline for post stroke depression or improvement of recovery following institutional protocol and those not receiving any SSRI were include. Assessment of cardiovascular risk factors, neurological deficits (NIHSS), symptoms of depression (Beck’s depression inventory) and autonomic disturbances (autonomic symptom questionnaire) were assessed at baseline, discharge and after three months. Results: We present data from 61 patients (70 [20] years, median [IQR], NIHSS: 7.0 [6.0], 23 females) receiving sertraline post-stroke and 27 untreated patients (71.0 [21.0] years, NIHSS: 5.0 [3.0], 13 females). Cardiovascular risk profiles showed no differences between groups (p=ns). Patients treated with sertraline compared to untreated patients tended to achieve favorable functional outcome (3-month mRS 0-2) and functional independence (3-month mRS 0-1) more frequently (52% vs. 41.7% and 18% vs. 12.5%, p=ns) and displayed enhanced decrease of NIHSS scores from admission to discharge (24.1% vs. 17.3%, p<0.01). On multivariate regression models, sertraline tended to predict lower severity of autonomic (p=0.08, R 2 =0.63) symptoms after 3 months, independently of depressivity. Discussion: Our data support the hypothesis of improved functional recovery from AIS in patients receiving sertraline de novo after AIS which might in parts be mediated by modulation of autonomic pathways.