Are SSRIs safe in IHD? Int Clini PsychoPharm.May.2013.


Serotonin weakly potentiates platelet aggregation. SSRIs block the uptake of serotonin into platelets and this action may impair the platelet hemostatic response. What are the benefits and risk of SRIs in cardiovascular disorders?

Andrade Chittaranjan, Kumar B. Chethan and Surya Sandarsh review this question in this article.

Beneficial effects (IHD): SRI can inhibit platelets and reduce platelet/endothelial activation .This action can be dose dependent. These effects may be SRI specific ( ie nortriptyline did not show this effect).SSRIs can reduce  levels of C-reactive protein and interleukin-6  and thus improve endothelial function  in patients with IHD and comorbid depression.Citalopram inhibits collagen-induced platelet aggregation and activation.This  is suggested to be even more important than the inhibition of serotonin mediated aggregation .These properties may be an additional health benefit when using SRI agents to treat depression comorbid with IHD

Harmful effects?

Heart rate variability is decreased in depression and this is a risk factor for adverse cardiac events. Tricyclic antidepressants (TCAs) decrease HRV but  SRIs do not influence this index. Even though epidemiological data suggest incresaed obesity and cholesterol levels with SSRI, short-term trials indicate opposite effect.

SSRI can increase the risk of GI bleeding if combined with aspirin ( commonly used in those with IHD), Clopidogrel will be less effecive if prescribed with Fluoxetine ( clopidogrel is a prodrug that is activated by CYP2C19.Flouxetine nad flouxamine inhibit cyp2c19). synergistic serotonergic effects may trigger angina.

Outcome: Depression is associated with increased risk of IHD events. Successful treatment of depression with SRI  reduces this risk. TCAs might increase the risk.Swenson et al ‘s 2006 review of all studies (between 1967-2005) showed that there was no difference in the risk between SSRI and placebo groups for either serious or non serious  cardiovascular adverse events.

Cardiac failure:

SADHART-CHF multicenter trial showed that sertraline was not different from placebo in cardiovascular risk changes during trial. Fosbol et al 2009 study indicated that  co administration of SSRIs and b-blockers was associated with a higher risk of overall and cardiovascular death relative to the co administration of b-blockers and TCA. Several confounders may explain this association.


SSRIs inhibit platelet aggregation, reduce inflammatory mediator levels, improve endothelial function and may reduce the cardiovascular response to stress.SSRIs may increase the ejection fraction and improve other indices of cardiovascular functioning in IHD and heart failure.Clinical evidence suggests that, in general, SSRIs are safe in patients with IHD and may, in fact, reduce the risk of IHD events in patients with or without a previous risk of heart disease. The clinical data is less clear in patients with heart failure.

Summary of the article: 

Cardiovascular mechanisms of SSRI drugs and their benefits and risks in ischemic heart disease and heart failure.Chittaranjan A, Chethan KB, Sandarsh S.Int Clin Psychopharmacol. 2013 May;28(3):145-55.

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