Antidepressants from SSRI or SNRI Classes Were Safe for Most Stroke Survivors

Kent P. Simmonds, DO, PhD

Credit: University of Texas Southwestern Medical Center

A new study found antidepressants in the selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) class did not increase the risk of hemorrhagic stroke or other serious bleeding events in most ischemic stroke survivors.¹

“Mental health conditions, such as depression and anxiety, are very common yet treatable conditions that may develop after a stroke,” said lead investigator Kent P. Simmonds, DO, PhD., from the University of Texas Southwestern Medical Center in Dallas, in a press release.² “Our results should reassure clinicians that for most stroke survivors, it is safe to prescribe SSRI and/or SNRI antidepressants early after stroke to treat post-stroke depression and anxiety, which may help optimize their patients’ recovery.”

Due to the fear of antidepressants increasing the risk of hemorrhagic stroke or other serious types of bleeding, clinicians may not prescribe SSRIs or SNRIs at all or early enough after a stroke when an individual has a high risk of depression or anxiety.

Stroke ranks as the fifth top cause of death when considered separately from other cardiovascular diseases, according to the American Heart Association’s Heart Disease and Stroke Statistics 2024 Update. This is behind diseases of heart, cancer, COVID-19, and unintentional injuries or accidents. About one-third of stroke survivors develop poststroke depression, which can affect quality of life if left untreated.

In their retrospective study, investigators examined the risk of serious bleeding among hundreds of stroke survivors who took different types of antidepressants after 1 year.¹ The secondary outcomes included hemorrhagic stroke, fall, and death.

The team leveraged electronic medical records data from 666,160 ischemic stroke patients from > 70 large healthcare centers in the US. Patients were treated at these healthcare centers for > 20 years.

The investigators looked at records from 2003 – 2023. In the sample, 35,631 took SSRI or SNRI antidepressants including sertraline, fluoxetine, citalopram, and venlafaxine, and 23,241 took other antidepressants. However, many of the patients were not taking any antidepressants.

The team defined serious bleeding as bleeding in the brain and digestive tract, as well as when bleeding prohibits the blood from reaching the body’s tissues.² Additionally, investigators assessed serious bleeding among participants who took antidepressants along with several types of blood-thinning medications used to prevent future blood clots.

These medications may include either anticoagulants or antiplatelet medications. Anticoagulants include medications such as warfarin, apixaban, and rivaroxaban. Antiplatelet medications can be prescribed as either a single medication (often aspirin) or 2 types of antiplatelet medications such as aspirin plus a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor.

The team found taking an SSRI and SNRI class of antidepressants along with anticoagulation medications did not increase the risk of hemorrhagic stroke or serious bleeding (bleeds: relative risk [RR], 1.01 (0.92 – 1.11); hemorrhagic stroke: RR, 1.01 (95% CI, 0.91 – 1.14).¹ However, they observed a 29% increased risk of hemorrhagic stroke among stroke patients taking anti-platelet medications, also known as dual anti-platelet therapy (DAPT) (RR, 1.29; 95% CI, 1.11 – 1.50).

Moreover, investigators found if ischemic stroke patients took antidepressants outside of the SSRI or SNRI classes—mirtazapine, bupropion, and tricyclics—there was a 15% increase in the risk of serious bleeding (RR, 1.15; 95% CI, 1.10 – 1.21).

Limitations highlighted by the investigators included the statistical methods used to adjust for differences among the groups may not have adjusted for all the important differences.² The study also did not consider the dosage, duration, or number of antidepressants the participants had taken.

“Maximizing rehabilitation early after a stroke is essential because recovery is somewhat time-dependent, and most functional gains occur during the first few months after a stroke,” Simmonds said. “Fortunately, dual antiplatelet therapy is often administered for 14, 30, or 90 days, so, when indicated, clinicians may not need to withhold antidepressant medications for prolonged periods of time. Future research should investigate the risk of bleeding associated with the use of anti-depressant and anxiety medications among patients with hemorrhagic or bleeding stroke.”

^References

1. ^{Simmonds, K. Chavez, A, Ifejika, N. Bleeding Risks for Acute Ischemic Stroke Patients on Serotonergic Antidepressants and Anticoagulation/Dual Anti-platelet Therapy. International Stroke Conference. 2024.}
2. ^{2 Common Types of Antidepressants Were Safe for Most Stroke Survivors. EurekAlert! February 1, 2024. https://www.eurekalert.org/news-releases/1032494. Accessed February 2, 2024.}