Antidepressants and platelet inhibition

[PikminOC]

I have a patient on Zoloft who is having a lot of bruising. Any antidepressants that don't have this side effect? I have looked it up and can't find ones that don't and I looked into tcas too, and they have it also. But maybe you guys will have more data

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[Stagg737]

I would have thought bupropion would be the best option given lack of serotonergic activity, but apparently a meta-analysis from 2018 says otherwise: Can we recommend mirtazapine and bupropion for patients at risk for bleeding?: A systematic review and meta-analysis

Other data is not great and somewhat conflicting but suggests a possible lower bleeding risk with SNRIs. Does your patient take other meds that can increase bleeding risk? If so, any way those medications could be changed to something with lower risk?

 

[ObsequiousAplomb]

I'm not basing this on any evidence other than my own biased recall, but I believe sertraline is more likely than others to cause this. I agree that looking at drug interactions and other culprits is a good first step.

I was also surprised to see that bupropion is not any better for this risk.

If you can't find any other causes for the bruising (and that may even include a workup that might involve hematology), I would consider trying rotating them to a different medication. Even if there isn't evidence on a population-level of much of a difference, the patient might not have bruising with a different medication. Then again, it might be worse.

 

[Sushirolls]

Increased bruising is in my usual R/B discussion with patients, but the one's who've noticed it, never felt it enough of an issue to want to change or discontinue.

 

[Batman's Underwear]

I have a patient on Zoloft who is having a lot of bruising. Any antidepressants that don't have this side effect? I have looked it up and can't find ones that don't and I looked into tcas too, and they have it also. But maybe you guys will have more data

I think you would have to avoid the ones that targets transporter. So in theory, Mirtazapine and Bupropion should be better but as Stagg737 mentioned, meta analysis from 2108 suggests otherwise. That being said, there are also newer studies suggesting mirtazapine and bupropion are associated with lower risk of bleeding.

I actually had a pt long time ago w/ ESRD on dialysis and chronic anemia with baseline hemoglobin of ~7.0 + intermittent transfusion. Previously on Zoloft, switched to low dose mirt, so far so good... I hope..

 

[PikminOC]

I would have thought bupropion would be the best option given lack of serotonergic activity, but apparently a meta-analysis from 2018 says otherwise: Can we recommend mirtazapine and bupropion for patients at risk for bleeding?: A systematic review and meta-analysis

Other data is not great and somewhat conflicting but suggests a possible lower bleeding risk with SNRIs. Does your patient take other meds that can increase bleeding risk? If so, any way those medications could be changed to something with lower risk?

Yes trazodone too

 

[aim-agm]

Trazodone decreases platelet serotonin only mildly (remember, it is fairly uniquely is a noncompetitive SERT inhibitor) so it shouldn't have much effect on function donation through that mechanism. (EDIT: On further review, Trazodone is also a decent 5HT2A antagonist and would block inhibit platelet function like mirtazapine would.)

Mirtazapine does not change platelet serotonin levels, but it does block the 5HT2A receptor which is where that serotonin needs to bind on platelets. Notably, this mechanism is potentially synergistic with SRIs (one decreases the amount of serotonin available to be released, the other antagonizes the activity of that serotonin) which may be important to consider as they are frequently used together, but admittedly I haven't looked at any studies on the matter. I suspect mirtazapine's alpha-2 antagonism also contributes to risk through altering hemodynamics.

Bupropion should have no direct effect on platelet function and should not affect bruising. It may affect bleeding risk, but remember that is a function of primary and secondary coagulation function, while bruising is really only primary coagulation (i.e. dependent on platelet function. I think it is reasonable to trial bupropion if patients are having trouble with bruising.

 

[Sikrouf]

Trazodone decreases platelet serotonin only mildly (remember, it is fairly uniquely is a noncompetitive SERT inhibitor) so it shouldn't have much effect on function donation through that mechanism.

Mirtazapine does not change platelet serotonin levels, but it does block the 5HT2A receptor which is where that serotonin needs to bind on platelets. Notably, this mechanism is potentially synergistic with SRIs (one decreases the amount of serotonin available to be released, the other antagonizes the activity of that serotonin) which may be important to consider as they are frequently used together, but admittedly I haven't looked at any studies on the matter. I suspect mirtazapine's alpha-2 antagonism also contributes to risk through altering hemodynamics.

Bupropion should have no direct effect on platelet function and should not affect bruising. It may affect bleeding risk, but remember that is a function of primary and secondary coagulation function, while bruising is really only primary coagulation (i.e. dependent on platelet function. I think it is reasonable to trial bupropion if patients are having trouble with bruising.

I though it was the sert blockade that prevented serotinin to get into platelets that was the culprit
How does the 5ht2a receptor affect their function ?

 

[clozareal]

Trazodone decreases platelet serotonin only mildly (remember, it is fairly uniquely is a noncompetitive SERT inhibitor) so it shouldn't have much effect on function donation through that mechanism.

Mirtazapine does not change platelet serotonin levels, but it does block the 5HT2A receptor which is where that serotonin needs to bind on platelets. Notably, this mechanism is potentially synergistic with SRIs (one decreases the amount of serotonin available to be released, the other antagonizes the activity of that serotonin) which may be important to consider as they are frequently used together, but admittedly I haven't looked at any studies on the matter. I suspect mirtazapine's alpha-2 antagonism also contributes to risk through altering hemodynamics.

Bupropion should have no direct effect on platelet function and should not affect bruising. It may affect bleeding risk, but remember that is a function of primary and secondary coagulation function, while bruising is really only primary coagulation (i.e. dependent on platelet function. I think it is reasonable to trial bupropion if patients are having trouble with bruising.

Combination therapy with an SSRI + alpha-2 antagonist (like mirtazapine) is superior to higher doses of monotherapy for acute depression, which is influencing my decision whether to increase dose vs switch a medication vs augment at lower doses.

Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression: A Systematic Review and Meta-analysis - PubMed

In this meta-analysis of RCTs comparing combinations of antidepressants with antidepressant monotherapy, combining antidepressants was associated with superior treatment outcomes but not with more patients dropping out of treatment. Combinations using an antagonist of presynaptic...

pubmed.ncbi.nlm.nih.gov

 

[hamstergang]

I though it was the sert blockade that prevented serotinin to get into platelets that was the culprit
How does the 5ht2a receptor affect their function ?

It's written there in that post: "5HT2A receptor which is where that serotonin needs to bind on platelets"

Serotonin enters platelets via the SERT, and when released it binds 5HT2A on platelets.

 

[ObsequiousAplomb]

Trazodone decreases platelet serotonin only mildly (remember, it is fairly uniquely is a noncompetitive SERT inhibitor) so it shouldn't have much effect on function donation through that mechanism.

Mirtazapine does not change platelet serotonin levels, but it does block the 5HT2A receptor which is where that serotonin needs to bind on platelets. Notably, this mechanism is potentially synergistic with SRIs (one decreases the amount of serotonin available to be released, the other antagonizes the activity of that serotonin) which may be important to consider as they are frequently used together, but admittedly I haven't looked at any studies on the matter. I suspect mirtazapine's alpha-2 antagonism also contributes to risk through altering hemodynamics.

Bupropion should have no direct effect on platelet function and should not affect bruising. It may affect bleeding risk, but remember that is a function of primary and secondary coagulation function, while bruising is really only primary coagulation (i.e. dependent on platelet function. I think it is reasonable to trial bupropion if patients are having trouble with bruising.

That's all a fine rationalization of a choice. I certainly thought the same way when the OP was started. The data linked earlier in this thread says otherwise though. This is an example of something that frustrates me a little in our field: a sophisticated explanation can convince us to do things that aren't supported by the science and still feel like we have a solid understanding.