Antidepressants and stroke: risk lower with strong serotonin reuptake inhibitors

  • Douros A & al.
  • Neurology
  • 7 Aug 2019

  • International Clinical Digest
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  • Use of strong vs weaker inhibitors of serotonin reuptake is associated with a somewhat lower risk for ischaemic stroke or transient ischaemic attack (TIA), but not myocardial infarction (MI).

Why this matters

  • High comorbidity of depression, cardiovascular disease.

Key results

  • Relative to users of antidepressants weakly inhibiting serotonin reuptake, users of strong inhibitors had lower ischaemic stroke/TIA rate (rate ratio [RR], 0.88; 95% CI, 0.80-0.97).
    • Effect size was attenuated in some sensitivity analyses.
  • No significant difference in MI rate (RR, 1.00; 95% CI, 0.87-1.15).
  • For selective serotonin reuptake inhibitors (SSRIs) alone, strong vs intermediate inhibitors:
    • Similar rate of ischaemic stroke/TIA (RR, 0.98; 95% CI, 0.92-1.04).
    • Borderline higher rate of MI (RR, 1.09; 95% CI, 1.00-1.18).

Study design

  • UK population-based cohort study of adult new users of SSRIs or third-generation antidepressants, mean follow-up of ~5.7 years.
  • Matching:
    • 15,860 cases of ischaemic stroke/TIA to 473,712 controls.
    • 8626 cases of MI to 258,022 controls.
  • Degree of inhibition:
    • Strong: duloxetine, fluoxetine, paroxetine, sertraline;
    • Intermediate: citalopram, escitalopram, fluvoxamine, venlafaxine;
    • Weak: mianserin, mirtazapine, nefazodone, reboxetine, agomelatine, viloxazine.
  • Main outcomes: stroke/TIA, MI.
  • Funding: Canadian Institutes of Health Research.


  • Residual confounding.
  • Specialist prescriptions not captured.
  • Possible outcome misclassification.

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