Efficacy of antidepressants in animal models of ischemic stroke

a systematic review and meta-analysis

Sarah K. McCann, Cadi Irvine, Gillian E. Mead, Emily S. Sena, Gillian L. Currie, Kieren E. Egan, Malcolm R. Macleod, David W. Howells

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3055-3063
Number of pages9
JournalStroke
Volume45
Issue number10
DOIs
Publication statusPublished - 31 Oct 2014

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Antidepressive Agents
Meta-Analysis
Animal Models
Stroke
Publication Bias
Neurogenesis
Serotonin Uptake Inhibitors
Brain Ischemia
Checklist
Publications
Therapeutics
Clinical Trials
Confidence Intervals
Depression

Keywords

  • animal
  • antidepressive agents
  • meta-analysis
  • models
  • review
  • stroke
  • systematic

Cite this

McCann, S. K., Irvine, C., Mead, G. E., Sena, E. S., Currie, G. L., Egan, K. E., ... Howells, D. W. (2014). Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis. Stroke, 45(10), 3055-3063. https://doi.org/10.1161/STROKEAHA.114.006304
McCann, Sarah K. ; Irvine, Cadi ; Mead, Gillian E. ; Sena, Emily S. ; Currie, Gillian L. ; Egan, Kieren E. ; Macleod, Malcolm R. ; Howells, David W. / Efficacy of antidepressants in animal models of ischemic stroke : a systematic review and meta-analysis. In: Stroke. 2014 ; Vol. 45, No. 10. pp. 3055-3063.
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Efficacy of antidepressants in animal models of ischemic stroke : a systematic review and meta-analysis. / McCann, Sarah K.; Irvine, Cadi; Mead, Gillian E.; Sena, Emily S.; Currie, Gillian L.; Egan, Kieren E.; Macleod, Malcolm R.; Howells, David W.

In: Stroke, Vol. 45, No. 10, 31.10.2014, p. 3055-3063.

Research output: Contribution to journalArticle

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T1 - Efficacy of antidepressants in animal models of ischemic stroke

T2 - a systematic review and meta-analysis

AU - McCann, Sarah K.

AU - Irvine, Cadi

AU - Mead, Gillian E.

AU - Sena, Emily S.

AU - Currie, Gillian L.

AU - Egan, Kieren E.

AU - Macleod, Malcolm R.

AU - Howells, David W.

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N2 - 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.

AB - 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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