Surprise finding: Antidepressants lower stroke risk!

Germany: Intake of stronger selective serotonin-reuptake inhibitor (SSRI) or third-generation antidepressant may be associated with a lower risk of stroke, finds a recent study published in the AAN journal Neurology.

According to the study, the use of antidepressants s strongly inhibiting serotonin reuptake may decrease the risk of ischemic stroke.

The researchers found a 12% reduced stroke risk among participants taking a stronger SSRI or third-generation antidepressant compared to those taking a weaker serotonin inhibitor.

In the general population, depression and cardiovascular disease are often comorbid. This comorbidity means antidepressants are commonly prescribed to patients who are at increased risk for ischemia. The cardiovascular safety of these drugs has been an ongoing concern.

Evaluating antidepressants beyond drug class may make sense in the assessment of cardiovascular effects, specifically, the affinity of individual agents for the serotonin-reuptake transporter.

Inhibition of serotonin transport into thrombocytes can interfere with their function, the researchers explain, "and antidepressants strongly inhibiting serotonin reuptake have been associated with an increased risk of major bleeding such as gastrointestinal bleeding and intracranial haemorrhage.

Christel Renoux, Lady Davis Research Institute in Montreal, Canada, and colleagues assessed whether the use of antidepressants with strong inhibition of serotonin reuptake is associated with a decreased incidence of ischemic stroke and myocardial infarction (MI).

The researchers conducted a retrospective cohort study with matched case controls. It involved 868,755 adults who had been newly prescribed an SSRI and another 69,633 who were taking a third-generation antidepressant between January 1, 1995, and June 30, 2014. Of the total cohort, 64% were women.

Duloxetine, fluoxetine, paroxetine, and sertraline were strong inhibitors; citalopram, escitalopram, fluvoxamine, and venlafaxine were classified as intermediate inhibitors; and mianserin, mirtazapine, nefazodone, reboxetine, agomelatine, and viloxazine were weak inhibitors.

During a mean 5.7 years of follow-up, 15,860 individuals were diagnosed with ischemic stroke or a transient ischemic attack (TIA). This translated to a crude incidence rate of 31.1 per 10,000 persons per year.

Key findings include:

• 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 the current use of weak inhibitors of serotonin reuptake, current use of strong inhibitors was associated with a decreased rate of ischemic stroke, but the effect size was smaller in some sensitivity analyses.


• The rate of MI was similar between strong and weak inhibitors.

"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," concluded the authors.

To read the complete study log on to https://doi.org/10.1212/WNL.0000000000008060