11:17 AM

483 - Antidepressants and GI Bleed, TIA Evaluation, Account Balance

Take 3 – Practical Practice Pointers©

From the Literature

1)   Increased GI Bleeding with Antidepressant Medications?


Selective serotonin reuptake inhibitors (SSRI) are an important part of our armamentarium to treat our patients with mental health issues. The National Health and Nutrition Examination Survey estimates 13.2% of Americans are taking antidepressants

– many of which are SSRIs.

Two recent systematic reviews highlight the possibility of gastrointestinal (GI) bleeding when SSRI medications are used in conjunction with other medications. Because clinical trials usually are done without including patients on multiple other medications or with significant comorbidities, we rely on this sort of research to alert us to problems with medications in real-world use.

The first review looked at the risk of GI bleeding from SSRIs combined with non- steroidal anti-inflammatory drugs (NSAIDs). This study examined two large databases and the Cochrane library for English-language articles. The authors had a clearly defined inclusion criteria (studies of patients on NSAIDs who began taking SSRI, vs. those who did not take SSRI), performed validity assessment of the articles and looked for sources of heterogeneity. Ten articles (over 66,000 patients) of decent validity (for cohort and case-control studies) were found and meta-analyzed. The relative risk of GI bleeding when an SSRI was added to NSAIDs was increased (RR 1.75, 95% CI: 1.32– 2.33) but had a significant amount of heterogeneity (I2 = 85.7%), which was not explained in the study. Despite the validity concerns, this review’s findings are consistent with previous research about this association.

The second review examined the risk of both GI and overall bleeding when SSRIs were given to patients on oral anticoagulants. This review was of higher quality – more databases were searched, and there was more detail about the finer points of the statistical analysis and sensitivity analyses. Fourteen studies were found, and eight studies with over 98,000 patients were included in the meta-analysis. They were of moderate to good quality. The risk of any major bleeding from a combination of any oral anticoagulant plus SSRI was increased (HR 1.35, 95% CI 1.14–1.58, I2 = 0%), but the risk of GI bleeding was only non-significantly increased. When direct oral anticoagulants (DOACs) were examined, the risk of any major bleeding was increased (HR 1.47, 95% CI 1.03–2.10, I2 = 13%). The studies not included in the meta-analyses due to methodologic heterogeneity also showed increased risks of both overall and GI bleeding. The authors of both reviews note that the absolute risk of bleeding is low, but because each review includes case-control studies, the rates cannot be estimated from the studies.

John’s Comments:

There is probably some signal here that should cause us to think carefully about our patients’ risk of GI and major bleeding on these medication combinations. Bleeding associated with SSRIs is thought to be due a serotonin deficiency in platelets due to a reuptake pathway that is blocked by these medications (I guess we need happy platelets to clot). It is neither practical nor wise to suggest that we can never use these combinations, but other bleeding risks such as age, previous bleeding, use of steroids, and any use of potentially protective (for GI bleeding) proton pump inhibitors should be factored into our decisions.


·       Alam SM, Qasswal M, Ahsan MJ, Walters RW, Chandra S. Selective serotonin reuptake inhibitors increase risk of upper gastrointestinal bleeding when used with NSAIDs: a systemic review and meta-analysis. Sci Rep. 2022;12:14452. Link

·       Rahman AA, He N, Rej S. Concomitant Use of Selective Serotonin Reuptake Inhibitors and Oral Anticoagulants and Risk of Major Bleeding: A Systematic Review and Meta-analysis. Thromb Haemost. 2023;123(01):054-063. Link

From the Literature and the American Heart Association (AHA)

2)     Rapid Evaluation for Suspected Transient Ischemic Attack (TIA)


Transient ischemic attack (TIA) is clinically described as an acute onset of focal neurological symptoms followed by complete resolution and is a significant risk factor for future stroke. In 2009, the American Heart Association redefined TIA using a tissue- based approach (ie, symptom resolution plus absence of infarction on brain imaging) rather than the time-based approach (ie, symptom resolution within 24 hours alone).

TIA is now widely understood to be an acute neurovascular syndrome attributable to a vascular territory that rapidly resolves, leaving no evidence of tissue infarction on diffusion-weighted imaging (DWI) MRI. A patient with resolved symptoms and MRI demonstrating infarct should be diagnosed with an ischemic stroke.

The AHA recently published a scientific statement regarding the diagnosis and initial treatment of TIA in the Emergency Department. A key aim of the scientific statement is to help clinicians properly risk-stratify patients with suspected TIA and determine which patients need to be admitted to the hospital and which patients might be safely discharged as long as proper and prompt follow-up has been arranged.

Considerations for Clinical Practice:

Diagnostic Evaluation – Imaging

·       Noncontrast CT (NCCT) is insensitive to rule out small acute ischemic strokes but can help rule out TI mimics (ie: mass lesions, acute bleed, subacute ischemia).

·       MRI with DWI is the preferred imaging modality to rule out acute infarct. If MRI with DWI can be obtained without delay for patients with TIA, NCCT can be safely avoided.

·       Evaluation of TIA requires adequate vascular imaging. Vessel imaging in the ED is warranted regardless of risk stratification score or likelihood of admission.

·       NCCT and CTA can be performed together to evaluate for hemorrhage and symptomatic stenosis.

·       CTA is safe in patients with chronic kidney disease, and the risk of acute kidney injury related to contrast administration is low.Duplex carotid ultrasound and transcranial Doppler are noncontrast options to evaluate cervical and intracranial vessels, respectively, but may not be available in the ED.

·       Extended cardiac monitoring in selected patients is helpful to evaluate for potential sources of cardiac embolism (atrial fibrillation).

·       Patients benefit from early neurology consultation, preferably in the ED or rapid follow-up within 1-week after the TIA.

Risk Stratification:

·       TIA risk stratification scales aid in the identification of high-risk patients and help guide disposition. Given their limitations, TIA risk stratification scales should be part of a more comprehensive evaluation.

·       The most widely used risk stratification tool is Age, Blood Pressure, Clinical Features, Duration, and Diabetes (ABCD2). It can be used to stratify patients into low-, moderate-, or high-risk groups.

Patient Disposition:

·       Presumed symptomatic (>50%) extracranial or intracranial stenoses warrant hospital admission. Acceptable disposition options include rapid ED TIA protocols with expedited referral to specialized cerebrovascular or TIA-specific clinics, admission to a 24-hour ED observation unit, or standard hospital admission.

·       To determine disposition of patients with TIA, consider short-term stroke risk on the basis of presentation and vessel imaging, timeliness of a reliable workup, availability of rapid outpatient follow-up, and the patient’s ability to return for rapid workup in a clinic setting.

·       Institutional and regional factors should guide protocols for the decision-making about disposition for patients with TIA.

Risk Reduction After TIA:

·       Maximal medical therapy includes antithrombotic therapy paired with blood pressure, glucose and lipid control with targets adherent to established guidelines.

·       The ABCD2 score can be used to guide antithrombotic regimens.

·       Attention to social influencers of health can aid in addressing health disparities.

Mark’s Comments:

Though this statement is targeting patients presenting to an ED, it serves as a good reminder regarding patients who may present in our clinics rather than presenting in the ED and the importance of expediting their work-up. The acronym BE FAST (Balance, Eyes [diplopia or monocular blindness], Face [weakness], arm [unilateral weakness], Speech [slurred or difficulty with], Time to call 911) is a helpful reminder regarding the diagnosis of TIA, and can help guide initial decisions even after the resolution of symptoms. Unfortunately, what it doesn’t provide is guidance for those who don’t have easy access to this technology or to a neurologist. Indeed, it doesn’t even acknowledge this as a possibility. For that we need to do what we’ve always done – the best we can.


Amin H, et al. Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association. Stroke. 2023;54:00–00. Published Ahead of Print 19 January 2023. Link

From PeerRxMed ( www.PeerRxMed.org )

3)     How’s the Balance of Your Emotional Bank Account?

“People don’t care how much you know until they know how much you care.”

Attributed to many persons

Pause for a moment before continuing your reading and think about a conflict you are presently or have recently been involved in (one will do), whether that be with a family member, friend, or work colleague. Consider the dynamics of that conflict – both the content and the overall “charge.” Now, continue reading.

They called it the “magic ratio” and it was 5:1. Research in the 1970s by John Gottman, PhD and Robert Levenson, PhD found that regardless of the conflict that existed in a marital relationship, if for every negative interaction during that conflict there were five or more positive interactions, that marriage was predictably a happy and stable one, even if there was no “resolution” to the conflict. And the closer the ratio was to 1:1, the more ominous that was for the long-term health of that relationship. In other words, it wasn’t whether they had conflict (all relationships do) but how they treated each other during that conflict that was important.

Subsequent research by Marcial Losada, PhD and Barbara Fredrickson, PhD extended those findings beyond conflict and marriage, and resulted in what they called the Losada ratio for other relationships, including friendships and business teams. While their precise mathematical calculation has subsequently come into question, the pattern is consistent: A ratio of somewhere between 3-6 emotional uplifts for every emotional withdrawal is necessary to create the conditions for thriving relationships, something that Stephen Covey, PhD famously called the “Emotional Bank Account.”

Now, stop again and consider the conflict that you brought to mind in the first paragraph. Any guesses as to what your “ratio” might be. Unless you are very consciously and deliberately making those positive deposits, your ratio is likely not close to 5:1, or even 3:1.

Fortunately, there are actions you can take that can help improve the “ratio” in your relationships so that you can build substantial emotional equity in your accounts.

According to the Gottman Institute, a good initial guide is to create regular opportunities to positively engage (“small things often”) even as you make immediate “repairs” (apologizing and “owning it”) when perceived damage is done. This engagement includes expressing curiosity, demonstrating active listening, articulating that you have their interests as well as your own in mind, honoring their perspective, expressing appreciation, finding opportunities for agreement,  and empathizing.  And, in the case of close relationships, a bit of well-timed and appropriately sensitive  humor can help as well.

Perhaps the first and most important step is to remember that regardless of the conflict, having healthy relationships with the people you spend time with regularly matters greatly, and therefore making regular life-enhancing deposits (remember, “small things often”) is likely the wisest investment you will ever make. Consider that this week as you are tempted to “go negative” in a conflict. You’ll be glad you did … and didn’t.


Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org