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September 03, 2019; 93 (10) Article

Degree of serotonin reuptake inhibition of antidepressants and ischemic risk

A cohort study

View ORCID ProfileAntonios Douros, Sophie Dell'Aniello, Golsa Dehghan, Jean-François Boivin, Christel Renoux
First published August 7, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008060
Antonios Douros
From the Centre for Clinical Epidemiology (A.D., S.D., G.D., J.-F.B., C.R.), Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics, and Occupational Health (A.D., C.R., J.-F.B.) and Department of Neurology and Neurosurgery (C.R.), McGill University, Montreal, Québec, Canada; and Institute of Clinical Pharmacology and Toxicology (A.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
MD, PhD
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  • ORCID record for Antonios Douros
Sophie Dell'Aniello
From the Centre for Clinical Epidemiology (A.D., S.D., G.D., J.-F.B., C.R.), Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics, and Occupational Health (A.D., C.R., J.-F.B.) and Department of Neurology and Neurosurgery (C.R.), McGill University, Montreal, Québec, Canada; and Institute of Clinical Pharmacology and Toxicology (A.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
MSc
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Golsa Dehghan
From the Centre for Clinical Epidemiology (A.D., S.D., G.D., J.-F.B., C.R.), Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics, and Occupational Health (A.D., C.R., J.-F.B.) and Department of Neurology and Neurosurgery (C.R.), McGill University, Montreal, Québec, Canada; and Institute of Clinical Pharmacology and Toxicology (A.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
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Jean-François Boivin
From the Centre for Clinical Epidemiology (A.D., S.D., G.D., J.-F.B., C.R.), Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics, and Occupational Health (A.D., C.R., J.-F.B.) and Department of Neurology and Neurosurgery (C.R.), McGill University, Montreal, Québec, Canada; and Institute of Clinical Pharmacology and Toxicology (A.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
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Christel Renoux
From the Centre for Clinical Epidemiology (A.D., S.D., G.D., J.-F.B., C.R.), Lady Davis Institute, Jewish General Hospital; Department of Epidemiology, Biostatistics, and Occupational Health (A.D., C.R., J.-F.B.) and Department of Neurology and Neurosurgery (C.R.), McGill University, Montreal, Québec, Canada; and Institute of Clinical Pharmacology and Toxicology (A.D.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
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Degree of serotonin reuptake inhibition of antidepressants and ischemic risk
A cohort study
Antonios Douros, Sophie Dell'Aniello, Golsa Dehghan, Jean-François Boivin, Christel Renoux
Neurology Sep 2019, 93 (10) e1010-e1020; DOI: 10.1212/WNL.0000000000008060

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Abstract

Objective To assess whether use of antidepressants with strong inhibition of serotonin reuptake is associated with a decreased incidence of ischemic stroke and myocardial infarction (MI).

Methods We conducted a cohort study using the UK Clinical Practice Research Datalink and considering new users of selective serotonin reuptake inhibitors (SSRIs) or third-generation antidepressants who were ≥18 years of age between 1995 and 2014. Using a nested case-control approach, we matched each case of a first ischemic stroke or MI identified during follow-up with up to 30 controls on age, sex, calendar time, and duration of follow-up. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) of each outcome associated with current use of strong compared with weak inhibitors of serotonin reuptake using conditional logistic regression.

Results The cohort included 938,388 incident users of SSRIs (n = 868,755) or third-generation antidepressants (n = 69,633). Mean age at cohort entry was 46 years (64% women). During follow-up, 15,860 cases of ischemic stroke and 8,626 cases of MI were identified and matched to 473,712 and 258,022 controls, respectively. Compared with current use of weak inhibitors of serotonin reuptake, current use of strong inhibitors was associated with a decreased rate of ischemic stroke (RR 0.88, 95% CI 0.80–0.97), but the effect size was smaller in some sensitivity analyses. The rate of MI was similar between strong and weak inhibitors (RR 1.00, 95% CI 0.87–1.15).

Conclusion Our large population-based study suggests that antidepressants strongly inhibiting serotonin reuptake may be associated with a small decrease in the rate of ischemic stroke.

Glossary

CI=
confidence interval;
CPRD=
Clinical Practice Research Datalink;
hdPS=
high-dimensional propensity score;
HR=
hazard ratio;
OR=
odds ratio;
RR=
rate ratio;
SSRI=
selective serotonin reuptake inhibitor

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received November 2, 2018.
  • Accepted in final form April 30, 2019.
  • © 2019 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response: Degree of serotonin reuptake inhibition of antidepressants and ischemic risk: A cohort study
    • Antonios Douros, Assistant Professor, Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital - McGill University
    • Jean-Francois Boivin, Professor Emeritus, Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital - McGill University
    • Christel Renoux, Assistant Professor, Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital - McGill University
    Submitted October 11, 2019
  • Reader response: Degree of serotonin reuptake inhibition of antidepressants and ischemic risk: A cohort study
    • Tomoyuki Kawada, Professor, Nippon Medical School
    Submitted September 09, 2019
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