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Trazodone causing Hypotension and Decreased Heart Rate?


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My pdoc is concerned because my BP and heart rate have been a bit low for awhile.....He seems to think Trazodone may be the culprit....Of course I had to consult Dr Google about it, and found that low blood pressure and decreased heart rate are possible side effects (mostly with long-term use).

I do have a home BP monitor, and my resting BP runs pretty low at times-- 88/45 for an example, and resting heart rate runs in upper 40s to lower 50s bpm.

I have tried to not obsess about this, and try to avoid taking my BP and pulse multiple times a day, but it's difficult....Worried now.

Anyway, I had never heard of these Trazodone side effects......I've been taking it almost 6 years at 200mg per night...It's my go-to med for sleep.......Pdoc wants to try tapering it down just a bit and see if that helps.

Anyone else experience this or heard of this with Trazodone?......Any thoughts appreciated....Thanks....

Oh, by the way, thyroid levels were tested and in normal range.....ECG showed no QT prolongation or any abnormalities other than the bradycardia.

@browri   @Iceberg

 

 

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4 hours ago, CrazyRedhead said:

My pdoc is concerned because my BP and heart rate have been a bit low for awhile.....He seems to think Trazodone may be the culprit....Of course I had to consult Dr Google about it, and found that low blood pressure and decreased heart rate are possible side effects (mostly with long-term use).

I do have a home BP monitor, and my resting BP runs pretty low at times-- 88/45 for an example, and resting heart rate runs in upper 40s to lower 50s bpm.

I have tried to not obsess about this, and try to avoid taking my BP and pulse multiple times a day, but it's difficult....Worried now.

Anyway, I had never heard of these Trazodone side effects......I've been taking it almost 6 years at 200mg per night...It's my go-to med for sleep.......Pdoc wants to try tapering it down just a bit and see if that helps.

Anyone else experience this or heard of this with Trazodone?......Any thoughts appreciated....Thanks....

Oh, by the way, thyroid levels were tested and in normal range.....ECG showed no QT prolongation or any abnormalities other than the bradycardia.

@browri   @Iceberg

 

 

When you say awhile... how did this get brought to his attention?

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15 hours ago, CrazyRedhead said:

My pdoc is concerned because my BP and heart rate have been a bit low for awhile.....He seems to think Trazodone may be the culprit....Of course I had to consult Dr Google about it, and found that low blood pressure and decreased heart rate are possible side effects (mostly with long-term use).

I do have a home BP monitor, and my resting BP runs pretty low at times-- 88/45 for an example, and resting heart rate runs in upper 40s to lower 50s bpm.

I have tried to not obsess about this, and try to avoid taking my BP and pulse multiple times a day, but it's difficult....Worried now.

Anyway, I had never heard of these Trazodone side effects......I've been taking it almost 6 years at 200mg per night...It's my go-to med for sleep.......Pdoc wants to try tapering it down just a bit and see if that helps.

Anyone else experience this or heard of this with Trazodone?......Any thoughts appreciated....Thanks....

Oh, by the way, thyroid levels were tested and in normal range.....ECG showed no QT prolongation or any abnormalities other than the bradycardia.

@browri   @Iceberg

So I may have figured this one out assuming that your signature is correct:

clonazepam 1mg AM + 2mg PM, trazodone 200mg, escitalopram 10mg, risperidone 1mg, vortioxetine 20mg

It's likely that the low heart rate occurs downstream of high occupancy of the SERT. 10mg of escitalopram is sufficient to do this:

https://pubmed.ncbi.nlm.nih.gov/30047786/

Serotonergic stimulation can lead to a suppression of norepinephrine and a subsequent reduction in heart rate. If this is possible with 10mg of escitalopram, then it's highly probable with that combined with 20mg vortioxetine and 200mg trazodone. Normally there are limits to that additive effect at SERT (i.e. adding another SERT inhibitor after reaching 90% occupancy with an existing one).

The blood pressure issue is slightly separate yet may simply be pronounced by the heart rate reduction. However, the reduced blood pressure, particularly on standing (orthostatic hypotension), is a result of both trazodone and risperidone combined. Hard to say which one is having more of an effect because I only have personal experience with risperidone. However, 1mg of risperidone is enough to cause significant orthostatic hypotension, and trazodone causes hypotension at most doses, which is how it actually mediates some of its sedative effect. Both risperidone and trazodone are potent a1 adrenergic antagonists, making them similar to prazosin, which was originally used to treat high blood pressure, but it and beta blockers have since been replaced with other agents. However, a1 antagonists are still used in some cases for PTSD, and beta blockers are sometimes prescribed for stage fright anxiety.

So the cardiac side effects taken together are the result of the cocktail as a whole. For sure though, your pdoc is onto it that trazodone is a central common factor. At 200mg it's both a SERT inhibitor AND an a1 adrenergic antagonist, both of which could be contributing to the problem in this case. You have three SERT inhibitors at play: trazodone, escitalopram, and vortioxetine. I see from your Dx's in your signature that you're being treated for a variety of treatment-resistant anxiety disorders + OCD in addition to MDD. This does typically require high SERT occupancy (~90%), which may result in bradycardia anyway. However, what I can say is that 20mg vortioxetine will achieve >80% SERT occupancy, and I imagine that 10mg escitalopram would get the rest. The added SERT inhibition that trazodone employs at higher doses isn't really needed and may just be contributing to bradycardia. Reducing the trazodone dosage by half should theoretically reduce the SERT inhibition while maintaining bedtime sedation (a1 antagonism) that is needed for sleep initiation in tandem with the risperidone and clonazepam.

In the long run, if reduction of trazodone to 100mg is tolerated but hypotension and/or bradycardia persist, a possibility might be considered to replace the trazodone with another sedative that doesn't mediate its effects via adrenergic antagonism. You are already taking 2mg clonazepam in the evening, which might limit what your pdoc is willing to prescribe as a sleep aid, but eszopiclone (Lunesta) would be an advisable option. Recent studies now show that it is capable of improving mood and anxiety symptoms in addition to its positive impacts on sleep. And you may not need much of it if you're taking it with clonazepam at night.

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13 hours ago, Iceberg said:

When you say awhile... how did this get brought to his attention?

I have a blood pressure monitor......I told him I was noticing lower than normal resting BP about maybe 3-4 months ago.,

The lower end of "normal" is generally considered to be 90/60......If systolic and diastolic drop below those numbers, it is generally considered to be hypotension...(too low).

I have no symptoms of it, though....No dizziness or fainting, etc.

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56 minutes ago, CrazyRedhead said:

I have a blood pressure monitor......I told him I was noticing lower than normal resting BP about maybe 3-4 months ago.,

The lower end of "normal" is generally considered to be 90/60......If systolic and diastolic drop below those numbers, it is generally considered to be hypotension...(too low).

I have no symptoms of it, though....No dizziness or fainting, etc.

would it be worth running it by your primary? if youre worried about other conditions, that might be the best way to rule non psych med things out 

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33 minutes ago, Iceberg said:

would it be worth running it by your primary? if youre worried about other conditions, that might be the best way to rule non psych med things out 

That's what I'm planning to do....I have an appointment for my annual physical in early December with my GP, so I will bring it up then with her.

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4 hours ago, browri said:

So I may have figured this one out assuming that your signature is correct:

clonazepam 1mg AM + 2mg PM, trazodone 200mg, escitalopram 10mg, risperidone 1mg, vortioxetine 20mg

It's likely that the low heart rate occurs downstream of high occupancy of the SERT. 10mg of escitalopram is sufficient to do this:

https://pubmed.ncbi.nlm.nih.gov/30047786/

Serotonergic stimulation can lead to a suppression of norepinephrine and a subsequent reduction in heart rate. If this is possible with 10mg of escitalopram, then it's highly probable with that combined with 20mg vortioxetine and 200mg trazodone. Normally there are limits to that additive effect at SERT (i.e. adding another SERT inhibitor after reaching 90% occupancy with an existing one).

The blood pressure issue is slightly separate yet may simply be pronounced by the heart rate reduction. However, the reduced blood pressure, particularly on standing (orthostatic hypotension), is a result of both trazodone and risperidone combined. Hard to say which one is having more of an effect because I only have personal experience with risperidone. However, 1mg of risperidone is enough to cause significant orthostatic hypotension, and trazodone causes hypotension at most doses, which is how it actually mediates some of its sedative effect. Both risperidone and trazodone are potent a1 adrenergic antagonists, making them similar to prazosin, which was originally used to treat high blood pressure, but it and beta blockers have since been replaced with other agents. However, a1 antagonists are still used in some cases for PTSD, and beta blockers are sometimes prescribed for stage fright anxiety.

So the cardiac side effects taken together are the result of the cocktail as a whole. For sure though, your pdoc is onto it that trazodone is a central common factor. At 200mg it's both a SERT inhibitor AND an a1 adrenergic antagonist, both of which could be contributing to the problem in this case. You have three SERT inhibitors at play: trazodone, escitalopram, and vortioxetine. I see from your Dx's in your signature that you're being treated for a variety of treatment-resistant anxiety disorders + OCD in addition to MDD. This does typically require high SERT occupancy (~90%), which may result in bradycardia anyway. However, what I can say is that 20mg vortioxetine will achieve >80% SERT occupancy, and I imagine that 10mg escitalopram would get the rest. The added SERT inhibition that trazodone employs at higher doses isn't really needed and may just be contributing to bradycardia. Reducing the trazodone dosage by half should theoretically reduce the SERT inhibition while maintaining bedtime sedation (a1 antagonism) that is needed for sleep initiation in tandem with the risperidone and clonazepam.

In the long run, if reduction of trazodone to 100mg is tolerated but hypotension and/or bradycardia persist, a possibility might be considered to replace the trazodone with another sedative that doesn't mediate its effects via adrenergic antagonism. You are already taking 2mg clonazepam in the evening, which might limit what your pdoc is willing to prescribe as a sleep aid, but eszopiclone (Lunesta) would be an advisable option. Recent studies now show that it is capable of improving mood and anxiety symptoms in addition to its positive impacts on sleep. And you may not need much of it if you're taking it with clonazepam at night.

So, to sum it all up in general. I guess I have too much serotonin going on?.......It's strange that i have no typical hypotension symptoms like dizziness or fainting, though.

So my pdoc is correct in trying to first reduce the trazodone dose?......He wants me to taper trazodone by 25 mgs per month....Personally he thinks that reducing it any faster could cause too many side effects.....Does this seem to be a reasonable taper?......His goal is to reduce total dose to 100mg, and see if that helps.

For the last 2 nights I have done 175mg, and so far no withdrawal symptoms at all.......My fear is that I won't be able to sleep on just 100mg....But I guess I'll have to deal with that when the time comes if that's the case.

I have tried Lunesta at max dose, and it didn't seem to do much for sleep for me personally......I was hoping it would work, but no such luck....I don't know if there are many other options for me as far as sleep medicines, except maybe Belsomra....I have tried so many meds for sleep, as indicated by my "ex-meds" list.

I guess other options might be to eliminate escitalopram or risperdone completely, since I am on relatively low doses already, but that might not be doable because of all the anxiety stuff going on with me.

Oh well, for now I will taper the Traz as planned, and see how it goes.....As I told @Iceberg, I do have my annual physical with my GP in early December, so I will bring this up with her, and see if there could be other possible causes for the hypotension and bradycardia.

Thanks for your insight.

 

Edited by CrazyRedhead
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On 11/16/2021 at 12:01 PM, CrazyRedhead said:

So, to sum it all up in general. I guess I have too much serotonin going on?

Well specifically I think the bradycardia is a result of high serotonergic stimulation. 

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

.......It's strange that i have no typical hypotension symptoms like dizziness or fainting, though.

Not everyone has symptoms of hypotension if their BP is a little low. Orthostatic hypotension (on standing) is typically noticed more because it's a sudden change in pressure. However, if blood pressure is generally low all the time and it isn't too low, it's possible you wouldn't notice except maybe feeling a little tired or sedated.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

So my pdoc is correct in trying to first reduce the trazodone dose?......He wants me to taper trazodone by 25 mgs per month....Personally he thinks that reducing it any faster could cause too many side effects.....Does this seem to be a reasonable taper?......His goal is to reduce total dose to 100mg, and see if that helps.

Yep, 100mg sounds like a good target. And reducing by 25mg per month sounds perfectly cautious to me. Disturbing sleep in any mental health condition is detrimental, and maintaining good sleep hygiene is integral to maintaining control over symptoms during the day. So going slowly with any sedative reduction is important so as not to induce any rebound. Particularly with trazodone is the pronounced alpha-1 adrenergic antagonism mentioned previously, but also the antihistamine effects are important for both sleep and, to a lesser extent, control of anxiety symptoms during the day. A rapid reintroduction of alpha-1 adrenergic and histaminergic stimulation could be somewhat activating and uncomfortable.

At 100mg trazodone should be less of a SERT inhibitor while still maintaining similarly significant alpha-1 adrenergic and histaminergic blockade to 200mg. The hope is that this may ease up the bradycardia. Downstream of that may be a slight increase in blood pressure as well.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

For the last 2 nights I have done 175mg, and so far no withdrawal symptoms at all.......My fear is that I won't be able to sleep on just 100mg....But I guess I'll have to deal with that when the time comes if that's the case.

It's possible but less likely. Even if the SERT inhibition is reduced at 100mg, alpha-1 adrenergic receptors and type 1 histamine receptors should still be saturated, which should still make for some pretty significant sedation in combination with 2mg clonazepam. You are right, though, that you'll just have to deal with things as they come and not think too much about it in the meantime. 25mg reduction per month is a very slow reduction, and the hope is that you don't notice any change because of how slowly it's being done.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

I have tried Lunesta at max dose, and it didn't seem to do much for sleep for me personally......I was hoping it would work, but no such luck....

This is interesting and always worth remembering. If eszopiclone (Lunesta) doesn't help, then zolpidem (Ambien) likely doesn't work either, and a specialty option like sodium oxybate (Xyrem / synthetic GHB) likely would be an imperfect treatment as well. The fact that trazodone works where "Z" drugs fail indicates that the alpha-1 adrenergic and histaminergic antagonism of trazodone are part of what helps you get to sleep. This of course would be in combo with the sedative effects of clonazepam.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

I don't know if there are many other options for me as far as sleep medicines, except maybe Belsomra....I have tried so many meds for sleep, as indicated by my "ex-meds" list.

If reducing the trazodone to 100mg is too low a dose to get you to sleep at night, then I would say return to the lowest dose that did get you to sleep and stay there until you can talk to your pdoc. If the bradycardia and hypotension are still bothersome and eszopiclone or zolpidem are ineffective, then suvorexant (Belsomra) or lemborexant (Dayvigo) would definitely be indicated. If you tolerate either orexin antagonist, you could theoretically take either of them for long-term insomnia management.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

I guess other options might be to eliminate escitalopram or risperdone completely, since I am on relatively low doses already, but that might not be doable because of all the anxiety stuff going on with me.

I suppose it comes down to what your pdoc sees as their purpose. Like I pointed out in a previous post, treatment-resistant anxiety and OCD are prominent Dxs for you, and these require high SERT occupancy. The 20mg vortioxetine should get you most of the way there, but the escitalopram MIGHT be needed to close the gap. There's a lot of compelling evidence that higher doses than the max dose of vortioxetine and vilazodone can be employed for things like OCD. Think 80mg vilazodone or 30-40mg vortioxetine. However, because vortioxetine is still only available as brand name Trintellix, most insurance companies have quantity limits keeping you from dosing it any higher. I will say, though, that my prescription plan through work doesn't have any quantity limits on Trintellix for some reason, and I don't think my plan for next year does either. If your insurance company will pay for it, you might want to consider talking to your pdoc about instead just eliminating escitalopram altogether and pushing the vortioxetine to >20mg. It could stand to really simplify your cocktail, and vortioxetine is an extremely robust serotonin booster relative to escitalopram or trazodone. So increasing vortioxetine to 30mg or 40mg may make up for the missing escitalopram. While this COULD make bradycardia worse, vortioxetine is a significant 5HT3 antagonist, which induces release of norepinephrine, and this effect is counter to SERT inhibition, which normally leads to a downregulation in norepinephrine.

I imagine if your pdoc is using risperidone specifically for the OCD that he may not want to discontinue that, and it's probably helping more than it's hurting at this point. So if your insurance will cover daily doses of vortioxetine greater than 20mg, then eliminating escitalopram progressively while you increase the vortioxetine will simplify your cocktail and it MIGHT help with the cardiac side effects.

On 11/16/2021 at 12:01 PM, CrazyRedhead said:

Oh well, for now I will taper the Traz as planned, and see how it goes.....As I told @Iceberg, I do have my annual physical with my GP in early December, so I will bring this up with her, and see if there could be other possible causes for the hypotension and bradycardia.

Thanks for your insight.

Fingers crossed that the trazodone taper to 100mg over the next few months goes easily for you, that 100mg is enough to help you sleep, and that reducing the dose eases some of the cardiac side effect. Then none of what I said really matters. 😄

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57 minutes ago, browri said:

 Fingers crossed that the trazodone taper to 100mg over the next few months goes easily for you, that 100mg is enough to help you sleep, and that reducing the dose eases some of the cardiac side effect. Then none of what I said really matters. 😄

Thank you..

I'm actually satisfied with a slow reduction, especially with a dose I've been on for nearly 6 years.....I definitely want to reduce dosage without having any sleep disturbances.

 I've tried Ambien, too, and just like Lunesta, it didn't work......It's good to know that I have 2 other options if 100mg trazodone doesn't work....I have heard of Belsomra, but Dayvigo must be pretty new.....Still hoping though, that the 100mg trazodone will still work.

I will have to check with my insurance company to see if can get more than 20mg Trintellix, and talk to pdoc about it......If I can simplify my cocktail, that would be excellent.

Yes, pdoc is prescribing the risperdone for the OCD......In light of that, he probably would not want to discontinue it.

What you said does matter........You have helped me a lot in understanding what's going on......I appreciate it so much, and thank you again..!!

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23 hours ago, CrazyRedhead said:

I will have to check with my insurance company to see if can get more than 20mg Trintellix, and talk to pdoc about it......If I can simplify my cocktail, that would be excellent.

Truly, if your insurance company is willing to cover higher doses of Trintellix than 20mg, then go for it, because it will probably allow you to eliminate escitalopram in the long run. In all honesty though, your insurance company probably wouldn't even notice that you were taking higher doses of Trintellix because you would never be filling a prescription that exceeds a quantity limit if they exist:

25mg = 1x20mg + 1x5mg

30mg = 1x20mg + 1x10mg

35mg = 1x20mg + 1x10mg + 1x5mg

40mg <== This is where it would get tricky because you would need 2x20mg tablets.

From my personal experience with Trintellix, my insurance company never looked at my Trintellix fills too closely because 15mg requires 1x5mg + 1x10mg. So I would actually fill 30x5mg tablets and 30x10mg tablets per month. 10mg was too low for me and 20mg was sometimes too high. My insurance company never batted an eye. There were quantity limits so that I couldn't have more than one tablet per day of each Trintellix tablet strength. But there was nothing stopping me from filling two different strengths in the same 30-day period.

So if your pdoc is interested in helping you consolidate your regimen, pushing Trintellix higher and slowly eliminating the escitalopram would be a good place to start because you might not get much resistance from insurance.

23 hours ago, CrazyRedhead said:

Yes, pdoc is prescribing the risperdone for the OCD......In light of that, he probably would not want to discontinue it.

Combining a high-dose SERT inhibitor like vortioxetine with a serotonin-dopamine antagonist like risperidone is actually probably some of the best pharmacotherapy you can get for treatment-resistant OCD.

Some of the best treatment strategies for OCD call for ultra-high occupancy of the serotonin transporter (SERT) greater than 80% and pushing more into the 90% range. However, modern psychopharmacology is now pretty sure that the positive effect this has on OCD is actually due, at least in part, to a net reduction in norepinephrine and dopamine signaling that happens when you inhibit the serotonin transporter. So newer treatment strategies for OCD may include dopamine antagonists, because it is suspected that calming dopamine signaling more directly will have additional positive effect in OCD due to the suppressive effect that this can have on the fear center in tandem with a SERT inhibitor. I believe quetiapine (Seroquel) is sometimes also used this way.

This effect on norepinephrine and dopamine is actually likely what causes the emotional blunting seen with most SSRIs. So this brings up an interesting point for vortioxetine, which may possibly cause less emotional blunting than most antidepressants, and this is likely because vortioxetine can actually enhance norepinephrine and dopamine transmission in other ways to offset the inhibitory effect of blocking the SERT. So more data will probably need to be gathered with time to confirm that vortioxetine does have similar positive effects in high doses on treatment-resistant OCD despite the way it enhances norepinephrine and dopamine neurotransmission. If it were able to have the same positive effect in OCD and similarly lead to less emotional blunting at the same time, this would be ideal, but not a lot of testing has been done in these patients. Alternatively if the enhancing effect on norepinephrine and dopamine were to negate the positive impact on OCD, risperidone would still have a direct calming effect downstream on norepinephrine by blocking alpha-1 receptors and dopamine by blocking D2 receptors to help balance all that out.

23 hours ago, CrazyRedhead said:

What you said does matter........You have helped me a lot in understanding what's going on......I appreciate it so much, and thank you again..!!

Of course. I only mean to say that hopefully things are simpler in the long run than having to speculate about the what-ifs.

Glad I could provide some insight into the mechanics though. Hopefully your titration goes smoothly. :) 

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