Do SSRIs Increase Bleeding Risk?

Last updated: February 6, 2019

Host: Wegdan Rashad, MD

Today’s question is: Do SSRIs increase the risk of bleeding?

Here is a summary of this episode:

  • Prescribe SSRIs with caution in patients with a defect in platelet number or function and those with H.pylori infection.
  • Concomitant SSRI and NSAID use is only of concern in patients taking daily and/or high doses.
  • Avoid prescribing fluvoxamine with warfarin. There are no other warnings regarding the use of SSRIs and anticoagulants.
  • It is generally not recommended to stop an SSRI before delivery and the absolute risk of postpartum bleeding is insignificant except in patients with a bleeding diathesis.

Transcript

Hello! I’m Dr. Wegdan Rashad and you are listening to the Psychopharmacology Institute podcast. We’ll be discussing topics that matter to you, the mental health clinician, in your practice, sharing expert opinions and the latest research.

Here’s a case for you.
A 61-year-old man presents with symptoms of depression. After meticulous history, clinical examination and work up he was diagnosed with major depressive disorder. The patient has a history of coronary artery disease and is taking 100 mg aspirin daily for the past 5 years. The question is: if we give this patient an SSRI would it increase his risk of bleeding?

What do you think? Dispersed in today’s episode will be clues to answering this case, so listen closely. We will cover GI, perioperative, CNS and postpartum bleeds with SSRIs.

Ready?

About 4 episodes ago we spoke about psychotropics and the GIT with Dr. James Levenson. He is a Professor of Psychiatry and the Department Chair of Consultation-Liaison at the Virginia Commonwealth University School of Medicine. So take a listen to the recap on GIT bleeds with SSRIs.

Dr. Levenson:
The data vary but there does seem to be a 1.5 to doubling increase in the relative risk but the absolute risk of a gastrointestinal hemorrhage remains small. The risk is increased with concomitant nonsteroidal anti-inflammatory drugs. Caution is advised in patients who are taking multiple drugs that can impair platelets. And what I would call high-risk patients are those patients with marked thrombocytopenia, for example, a platelet count under 25,000. Patients with that low a platelet count are at risk for spontaneous bleeding. And I would also urge caution in the prescription of SSRIs in patients who have a normal number of platelets but who have dysfunctional platelets like in the inherited disorder Von Willebrand’s disease. And we should mention that there are rare cases of SSRIs themselves causing thrombocytopenia.

So despite the fact that SSRIs can double the relative risk of GI bleeds, the absolute risk is small. In people with an impaired number or function of platelets, however, we should be cautious. Now, Dr. Levenson mentioned nonsteroidal anti-inflammatory drugs. If your patient takes the occasional aspirin, are they still at risk? My Psychopharm Institute colleague, Dr. Dana Wang, investigates.

Dr. Wang:
Dr. Levenson, you have reported that GI bleeding risk increases significantly with chronic use of antiplatelet and SSRI together. How about sporadic antiplatelet use? Is it still relatively contraindicated? Say a patient on SSRI gets headaches often, but he or she does not want to take acetaminophen, would the occasional PRN use of ibuprofen or another NSAID pose significant GI bleeding risks?

Dr. Levenson:
So, clinically I think there is little reason for concern in someone who is not at baseline high risk for bleeding if they take an SSRI and gets a headache and wants to take ibuprofen or another nonsteroidal anti-inflammatory drug. The increased risk of gastrointestinal bleeding in the combination of the two comes from studies where patients were taking nonsteroidal anti-inflammatory drugs every day for a sustained period. Those are typically patients who are taking higher doses most often to treat arthritis or other forms of chronic pain. So, no, I don’t think there is a reason to worry in somebody who wants to take an SSRI for a temporary symptom.

So, in a nutshell, no worries with the occasional NSAID user.

Here is another question you might have thought of. You have a patient with no platelet problems BUT does take a blood thinner like warfarin. Do SSRIs pose a risk here?

Dr. Levenson:
The reports are mixed. I’m reassured that the US Food and Drug Administration does not warn of this interaction. I would avoid prescribing fluvoxamine in a patient on warfarin because fluvoxamine does increase warfarin levels by inhibiting 2D9. But that’s a different mechanism than interfering with platelet function. There appears no increased risk with heparin or enoxaparin. And to date, I have been unable to find any information, any cases of SSRIs causing gastrointestinal bleeding with the newer anticoagulants like etexilate, dabigatran, rivaroxaban, and apixaban. And given how often SSRIs are prescribed and the fact that these drugs don’t act via platelets, they probably are safe to administer together.

So, avoid fluvoxamine with warfarin. Otherwise, there is no warning against using SSRIs with other blood thinners.

Now let’s move on to the risk of perioperative bleeds and SSRIs.

Dr. Levenson:
A systematic review of 13 studies concluded that serotonergic antidepressants increase the risk or perioperative bleeding with the odds ratios between 1.2 and 4. But again, the actual amount of blood lost was small. So the bottom line here for perioperative bleeding risk with SSRIs is that there probably is a small increased relative risk. The absolute risk is quite small and it’s unlikely clinically significant except in those high-risk patients.

So, if your patient is taking an SSRI and has to get surgery. His or her risk is increased but the actual amount of blood loss is likely to be small.

So we have covered GI and perioperative bleeds with SSRIs. Now we arrive to CNS bleeding. I know of patients who develop post-stroke depression and the treatment is usually an SSRI. Now, this is weird. Could the very drug we use to treat post-stroke depression predispose to a hemorrhagic stroke?

Dr. Levenson:
Finally, another study showed that after patients had an ischemic stroke and were started on an SSRI for post-stroke depression, they had an increased risk of GI bleeding, no increased risk of intracranial hemorrhage and a reduction in cardiovascular events.

Aha! So an SSRI, in this study, would increase the risk for GI but not intracranial bleeds. Dr. Levenson goes on to discuss that the evidence is murky and difficult to interpret with some studies showing an increased albeit small risk of bleeding.

Dr. Levenson:
One reason for the murkiness in this data, the difficulty interpreting it is that depression and anxiety themselves have been independently associated with risk for hypertension and risk for stroke. And so antidepressants appearing to be associated with an increased risk of stroke may really be a marker for depression and anxiety as the cause of increased risk. Finally, one study showed a very small, that tried a control for this effect of depression and anxiety found a very small relative increased risk with SSRIs versus tricyclics.

So this is what is called confounding by indication. The depression and anxiety may contribute to the increased risk of stroke and not just the SSRIs alone are the culprits. However, studies that controlled for this still found an increased risk of bleeding relative to TCAs.

And this is why we need to be wise and weigh out the risks of prescribing psychotropics. If a patient (especially if at risk for bleeding) has a chance to improve with psychosocial interventions, it is better to try that first.

Imagine an 8-months-pregnant patient on sertraline asks you whether she’s at increased risk of bleeding during childbirth or not. What would you say?

Let’s check in with Dr. Levenson.

Dr. Levenson:
This has been much less studied. But the few data we have are mixed, both data showing an increased risk and data showing no increased risk. And the systematic review that tried to look at this systematically concluded the same thing that we’re not sure. But just as an illustration of how difficult it can be to interpret such studies, another recent systematic review found that antidepressants were associated with a small increased relative risk but it was unrelated to how much they influence serotonin which tends to suggest that the increased risk may have nothing to do with the antidepressants at all. So bottom line for postpartum bleeding: There are a few data. What data we have pointed to a small increased relative risk at most and very small absolute risk, unlikely that it’s clinically significant except in high-risk patients. We generally do not recommend stopping an SSRI shortly before delivery or cesarean section because this increases risk for the precipitation of postpartum depression.

And there you have it. Generally, it is not recommended to stop an SSRI before delivery and the absolute risk of extra bleeding is insignificant EXCEPT in high-risk patients with a bleeding diathesis. It seems wise though to identify early on whether your patient has a bleeding problem and to coordinate with her gynecologist.

We are nearing the end of our podcast today but before we go, we need to answer the case. A 61-year-old man with depression, taking 100 mg aspirin daily and I asked you whether he is at increased risk of bleeding or not.

Well, according to what we heard from Dr. Levenson today, yes he is! He is at increased risk for GI bleeds and possible perioperative and CNS bleeds. He is considered a high-risk patient due to daily and long-term use of aspirin. So accordingly you would have to be very cautious prescribing him an SSRI.

And that’s about it for today. Now to wrap it up, here come the key points.

Key Points

  • The risk of GI bleeding with SSRIs is 1.5 to 2 times greater. Prescribe SSRIs with caution in patients with a defect in platelet number or function and those with H.pylori infection.
  • Concomitant SSRI and NSAID use is only of concern in patients taking daily and/or high doses.
  • Avoid prescribing fluvoxamine with warfarin. There are no other warnings regarding the use of SSRIs and anticoagulants.
  • For perioperative bleeding risk with SSRIs, there is a small, increased relative risk. It’s likely to be clinically insignificant except in high-risk patients.
  • There are mixed results on the risk of CNS bleeding with SSRIs. This may be due to anxiety and depression acting as confounding factors.
  • It is generally not recommended to stop an SSRI before delivery and the absolute risk of extra bleeding is insignificant except in high-risk patients with a bleeding diathesis.

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If you are a psychotherapy provider, check out our sister-platform Psychotherapy Academy for lectures and content to help you become a better therapist. Visit psychotherapyacademy.org

The following people participated in this episode: Dr. Flavio Guzman as the general editor, Mark Young as the audio engineer, Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. We’d also like to thank Dr. James Levenson, and Dr. Dana Wang, for being with us.

Thank you for joining us in today’s podcast until the next episode, goodbye!

References

  1. Jiang, H. Y., Chen, H. Z., Hu, X. J., Yu, Z. H., Yang, W., Deng, M., … & Ruan, B. (2015). Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clinical Gastroenterology and Hepatology, 13(1), 42-50.
  2. Quinn, G. R., Singer, D. E., Chang, Y., Go, A. S., Borowsky, L. H., Udaltsova, N., & Fang, M. C. (2014). Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin. The American journal of cardiology, 114(4), 583-586.

 

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