Sarah K McCann1, Cadi Irvine1, Gillian E Mead1, Emily S Sena1, Gillian L Currie1, Kieren E Egan1, Malcolm R Macleod2, David W Howells1. 1. From The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia (S.K.M., E.S.S., D.W.H.); and Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom (C.I., G.E.M., E.S.S., G.L.C., K.E.E., M.R.M). 2. From The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia (S.K.M., E.S.S., D.W.H.); and Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom (C.I., G.E.M., E.S.S., G.L.C., K.E.E., M.R.M). malcolm.macleod@ed.ac.uk.
Abstract
BACKGROUND AND PURPOSE: Poststroke depression is a prevalent complication of stroke with unclear pathogenesis. The benefits of antidepressants in this context and their effects on stroke recovery other than effects on mood are not clearly defined, with some studies suggesting efficacy in improving functional outcome in both depressed and nondepressed stroke patients. We have analyzed the preclinical animal data on antidepressant treatment in focal cerebral ischemia, modeled±depression, to help inform clinical trial design. METHODS: We performed a systematic review and meta-analysis of data from experiments testing the efficacy of antidepressants versus no treatment to reduce infarct volume or improve neurobehavioral or neurogenesis outcomes in animal models of stroke. We used random-effects metaregression to test the impact of study quality and design characteristics and used trim and fill to assess publication bias. RESULTS: We identified 44 publications describing the effects of 22 antidepressant drugs. The median quality checklist score was 5 of a possible 10 (interquartile range, 4-7). Overall, antidepressants reduced infarct volume by 27.3% (95% confidence interval, 20.7%-33.8%) and improved neurobehavioral outcomes by 53.7% (46.4%-61.1%). There was little evidence for an effect of selective serotonin reuptake inhibitors on infarct volume. For neurobehavioral outcomes there was evidence of publication bias. Selective serotonin reuptake inhibitors were the most frequently studied antidepressant subtype and improved neurobehavioral outcome by 51.8% (38.6%-64.9%) and increased neurogenesis by 2.2 SD (1.3-3.0). CONCLUSIONS: In line with current clinical data and despite some limitations, antidepressant treatments seem to improve infarct volume and neurobehavioral outcome in animal models of ischemic stroke.
BACKGROUND AND PURPOSE: Poststroke depression is a prevalent complication of stroke with unclear pathogenesis. The benefits of antidepressants in this context and their effects on stroke recovery other than effects on mood are not clearly defined, with some studies suggesting efficacy in improving functional outcome in both depressed and nondepressed stroke patients. We have analyzed the preclinical animal data on antidepressant treatment in focal cerebral ischemia, modeled±depression, to help inform clinical trial design. METHODS: We performed a systematic review and meta-analysis of data from experiments testing the efficacy of antidepressants versus no treatment to reduce infarct volume or improve neurobehavioral or neurogenesis outcomes in animal models of stroke. We used random-effects metaregression to test the impact of study quality and design characteristics and used trim and fill to assess publication bias. RESULTS: We identified 44 publications describing the effects of 22 antidepressant drugs. The median quality checklist score was 5 of a possible 10 (interquartile range, 4-7). Overall, antidepressants reduced infarct volume by 27.3% (95% confidence interval, 20.7%-33.8%) and improved neurobehavioral outcomes by 53.7% (46.4%-61.1%). There was little evidence for an effect of selective serotonin reuptake inhibitors on infarct volume. For neurobehavioral outcomes there was evidence of publication bias. Selective serotonin reuptake inhibitors were the most frequently studied antidepressant subtype and improved neurobehavioral outcome by 51.8% (38.6%-64.9%) and increased neurogenesis by 2.2 SD (1.3-3.0). CONCLUSIONS: In line with current clinical data and despite some limitations, antidepressant treatments seem to improve infarct volume and neurobehavioral outcome in animal models of ischemic stroke.
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