Mirtazapine helps POTS - or so it seems!

[Valentijn]

@SDSue - As has been mentioned above, Mirtazapine is an ADRA2A antagonist. Repressing ADRA2A can increase norepinephrine release or levels, which can raise blood pressure and/or pulse pressure. This can help with hypotension.

A list of drugs which have this action are at http://en.wikipedia.org/wiki/Alpha-2A_adrenergic_receptor - Some are much more specific in their actions than others. Yohimbine is the most specific, since it has a strong action at ADRA2A, 2B, and 2C and nothing else. Mirtazapine, on the other hand, has a stronger action on a Histamine receptor, and strong actions on seretonin receptors.

I don't get side effects from Yohimbe, but I take a pretty small dose. They usually come in 400mg capsules, and I split those into 4 100mg capsules and take it twice per day. If I take it past 2pm or so, it can be too over-stimulating to sleep, even with the small dose. I also test low for serum norepinephrine, which might be an indication for whether or not it's likely to be helpful.

If a low dose of yohimbe isn't helpful, and/or norepinephrine isn't low, there might be some other effect of the mirtazapine which was helpful, such as acting as an H1 antagonist.

 

[Sidereal]

Mirtazapine makes alpha 2 adrenergic (autoreceptor) antagonism more tolerable for people who are prone to overstimulation and anxiety because it also acts on several serotonin and histamine 1 receptors which causes sedation so the stimulating effect of raised norepinephrine is offset by the sedating effect of higher serotonin and lowered histamine.

I agree with @Valentijn regarding H1 antagonism. I find that the good old H1 antagonist benadryl is helpful for my orthostatic intolerance because the hypotensive effect of histamine from my mast cell activation disorder is treated by this drug. A normal person without a histamine problem would get hypotensive and tachycardic from benadryl; for me it does the opposite. Its antimuscarinic action also minimises the awful urge to urinate all the time, though it also causes side effects like dry mouth, blurry vision and sedation.

 

[wastwater]

I found mirtazapine one of the worst for me,it seemed to shut my brain down,got a good nights sleep then woke dead headed and didn't come around,couldn't think.

 

[SDSue]

A list of drugs which have this action are at http://en.wikipedia.org/wiki/Alpha-2A_adrenergic_receptor - Some are much more specific in their actions than others. Yohimbine is the most specific, since it has a strong action at ADRA2A, 2B, and 2C and nothing else. Mirtazapine, on the other hand, has a stronger action on a Histamine receptor, and strong actions on seretonin receptors.

Thanks, Val. This is confusing. I don't think it's the ADRA2A action, as I recently tested with a 2.5 mg capsule of pure Yohimbine. It was awful!!! My tachycardia increased along with heightened anxiety and other bad things I don't clearly recall. I just know I thought "I'll never take that again!" and put the bottle in my junk bin.

Are we opposites? Because I have a 60+ beat/min increase in HR along with a drop in pulse pressure (usually under 10), perhaps I've got more than one type of dysautonomia going on?

So, either I took way to much, or it's like Sidereal is saying here:

Mirtazapine makes alpha 2 adrenergic (autoreceptor) antagonism more tolerable for people who are prone to overstimulation and anxiety because it also acts on several serotonin and histamine 1 receptors which causes sedation so the stimulating effect of raised norepinephrine is offset by the sedating effect of higher serotonin and lowered histamine.

Theoretically, I could test by taking yohimbine with benadryl, but I'm not that brave.

The question that needs to be answered is whether or not I have hyperadrenergic POTS. I have the classic pattern but lack blood work verification during a TTT. What I do have from my TTT, however, is a cardiologist who patted my head and suggested that I relax and drink more wine (fortunately, my results were used to formally diagnose POTS once I got them in the proper hands.)

 

[Raines]

This is a very interesting thread, I took mitazapine for many years - because it helped me sleep I chose to put up with the other side effects (weight gain, and being a very unplesent moody b**** being the main ones).

I stoped taking it a couple of years ago and have noticed a marked delcine in my ME/CFS also have noticed some POTs like symptons for the first time

What a choice - feel halfway normal and want to slaughter people, or feel sick and let them live. Have you found anything else that works as well?

this is just so true - the horriable person I was when taking mitazapine- I have no idea how anyone put up with me.

 

[SDSue]

Last night, I repeated my combo of dextromethorphan 60 mg (as Deslym) and Mirtazapine 7.5 mg and once again, my POTS is much better. Alone, neither does as much, so I'm starting to think synergism here. (It's difficult to determine cause-effect because of the natural ups and downs of ME/CFS)

I checked for drug interactions and found this on Drugs.com:

Using dextromethorphan together with mirtazapine can increase the risk of a rare but serious condition called the serotonin syndrome, which may include symptoms such as confusion, hallucination, seizure, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea. Severe cases may result in coma and even death.

Clearly, my experiment warrants caution and a spin past my doctor, but this may be another clue about what's happening here. I can't tolerate SSRI's, so I'm not sure seratonin is the one of the mechanisms working for me. Who knows.

 

[adreno]

Mirtazapine won't cause serotonin syndrome (SS), even when combined with an SSRI. 5-HT2A antagonism is actually used as a treatment for SS.

 

[Sushi]

And how would Strattera fit into this discussion (if at all!). It was the one drug that virtually eliminated all my OI symptoms.

 

[PNR2008]

Remeron was a very bad drug for me, it made me hyper and could not sleep with it. Guaifenesin works well for my sinuses but I know I don't take enough of it, so the time release can be the answer. @zzz Goldstein personally recommended nimotop but it was so expensive at the time and no local Dr. would prescribe it for me. Do you know if it's reasonably priced now? Thanks.

 

[Sidereal]

And how would Strattera fit into this discussion (if at all!). It was the one drug that virtually eliminated all my OI symptoms.

Strattera works differently than mirtazapine to raise norepinephrine. It blocks reuptake of norepi from the synapse by blocking the norepi transporter thus making what norepi is available hang around for longer. This would make some patients much worse since we know that a subgroup have a deficiency in norepi transporter giving them too much norepi and orthostatic intolerance (and anxiety). Those who have too little norepi, say those with NMH whose BP and heart rate start to crash when standing due to excessive parasympathetic drive, would be expected to do well on this drug.

Strattera is also an NMDA receptor antagonist which according to some is a key area of pathology in this disease.

 

[SDSue]

@sidereel, I know I'm being dense here, but do you know how Strattera compares to Mirtazapine? It sounds like both raise NE but would the clinical effect be similar? @Sushi

 

[Sidereal]

@sidereel, I know I'm being dense here, but do you know how Strattera compares to Mirtazapine? It sounds like both raise NE but would the clinical effect be similar? @Sushi

Both raise norepi yes but the clinical effect may not at all be the same because of the serotonergic and histaminergic properties of mirtazapine we talked about earlier. If you really do have hyperadrenergic POTS I would imagine Strattera might make you feel awful.

 

[SDSue]

Thanks, @Sidereal . I'm just thrilled to have found a combo that's apparently working. Fingers crossed that it remains effective (or doesn't end up being just a "good" day in all this mess!)

 

[Sushi]

Those who have too little norepi, say those with NMH whose BP and heart rate start to crash when standing due to excessive parasympathetic drive, would be expected to do well on this drug.

That's me! My TTT showed that I have excessive parasympathetic activity.

Strattera is also an NMDA receptor antagonist which according to some is a key area of pathology in this disease.

Interesting! I stopped because my OI was better and it costs a lot, but it sure did work well for me.

 

[adreno]

@SDSue

Strattera targets both a1 and a2, whereas Mirtazapine targets only a1, because a2 is blocked. In that way mirtazapine works somewhat similar to midodrine, an a1 agonist used to treat POTS.

 

[meeKO]

This is really interesting although I'm straining to keep up with everyone's superior medical knowledge and terminology. We're looking for a breakthrough for my wife's POTS or NMH and recently, doing an inpatients stint on Ketamine actually helped the OI. Would this give anyone a clue as to what treatments might be best going forward? Really glad you've found something good @SDSue . What a difference it makes!

 

[adreno]

We're looking for a breakthrough for my wife's POTS or NMH and recently, doing an inpatients stint on Ketamine actually helped the OI.

If ketamine helped, you could try memantine, which is a commonly available NMDA antagonist.

 

[SDSue]

This is really interesting although I'm straining to keep up with everyone's superior medical knowledge and terminology. We're looking for a breakthrough for my wife's POTS or NMH and recently, doing an inpatients stint on Ketamine actually helped the OI. Would this give anyone a clue as to what treatments might be best going forward? Really glad you've found something good @SDSue . What a difference it makes!

Thanks. I'd love to hear more about the ketamine trial. How much, how often, what effects, etc. I sure hope they will allow your wife to continue use once she leaves the trial!

 

[meeKO]

How much, how often, what effects,

Through an IV via a PICC line. Gradual scaling up from 4 mg and doubling as she went around twice a day. As she's in the hospital they're always monitoring. 3 nights in she reached 28mg and had a hell of a time because they ramp down her pain meds and the Ketamine causes various side effects and the nurses didn't really understand her ME and Fibromyalgia so her medication was dropped too fast. We discharged her after 4 nights of the 7 night stint So it can help with getting off pain meds in a normal chronic pain patient but someone with CFS/ME finds the lack of rest in a hospital difficult to bounce back from. The OI thing was an unexpected side effect..
I don't think we can get ketamine as it's highly controlled in Australia.
If you have any more questions feel free to shoot em at us!
Thanks @adreno ! I'll ask about that too. Great knowledge.

 

[zzz]

Dr. Jay Goldstein found IV ketamine to be the most effective treatment for his ME/CFS, fibromyalgia, and IBS patients. @meeKO, I think you would find it very helpful to become familiar with his work; the thread Dr Jay Goldstein's Instant Remission ME/CFS Treatments can be a good place to start. Almost as good as IV ketamine is IV lidocaine, which can be much easier to obtain in some places. Proper lidocaine dosing can be found on page 46 of Dr. Goldstein's book Betrayal by the Brain:

I find IV lidocaine 200 to 300 mg in 500 ml of normal saline to be a rapidly effective analgesic in FMS patients.The effects sometimes last for days or weeks, perhaps by inducing long-term potentiation (see p. 65), and often global symptoms are improved. About half of my patients respond to this treatment after being refractory to all oral agents. IV lidocaine... has the unusual property of greater symptom relief and duration of action with each successive use, plateauing after four infusions, and lasting three to seven days.

For people who respond well to ketamine, the drugs in the box labeled "Ketamine ↑" in this chart are often very helpful. The chart is reproduced on page 458 of Dr. Goldstein's Tuning the Brain, and reading this book following Betrayal by the Brain is the best way to understand Dr. Goldstein's methods and treatments.