The POTS Pharmacopeia: Medications for Postural Orthostatic Tachycardia Syndrome

(citations needed)

I want to skip past lifestyle modifications straight to medications for POTS because I am so tired of hearing from people that the only interventions their doctors had to offer were salt, fluids, compression, exercise, and maybe beta blockers (the medications whose names usually end in -olol). There are no cures for POTS, but there are way more options out there for symptom management than many doctors know about or would have you believe. I have even heard of “POTS specialists” who only administer beta blockers! Infuriating!

This post is not intended to be comprehensive, but will cover many of the core medications used to treat POTS just so you can be aware of the possibilities that are out there. These medications are all used off-label for our condition, meaning that they have been formally approved for use in other conditions, but not ours; however, their general safety has been tested, and there is evidence that they work for us too. As always, discuss whether any medication is right for you — and compatible with comorbid conditions/treatments — with your doctor and pharmacist, and don’t forget to check my Legal page for disclaimers. I’m definitely not a doctor or a pharmacist, just a nerd who reads POTS research.

One important thing to be aware of is that your primary goal should be overall symptom reduction, and not just reduction of tachycardia (high heart rate). In a lot of people with POTS, that tachycardia is doing something; some portion of their tachycardia is a necessary compensation for low blood volume and/or lack of vasoconstriction. This is called secondary tachycardia. Some other portion of their tachycardia is an overreaction to being upright, just their bodies being extra, as most often happens in hyperadrenergic POTS; this is primary tachycardia. Medications like beta blockers that reduce heart rate are best at taking the edge off of POTS by reducing this “extra” tachycardia; in the case of secondary tachycardia, they can worsen symptoms even as they improve tachycardia by lowering the heart rate. If your heart is revving up because it’s desperately trying to get more blood throughout your brain and you slow it down too much, you will likely feel worse (see the beta blocker chapter in the POTS book edited by Gall et al.).

In the case of secondary tachycardia, an indirect approach is warranted: Address the low blood volume and/or lack of vasoconstriction, and your heart simply won’t have to try as hard anymore.

Because there are three main mechanisms through which POTS works — low blood volume, lack of vasoconstriction, and increased catecholamine (stress hormone) output — I follow Mar and Raj’s lead in organizing by subtype and dividing treatments up into “playbooks”: the hypovolemic, neuropathic, and hyperadrenergic playbooks.

A lot of people have mixed presentations of two or even all three of these subtypes of POTS; a strategy that has worked well for me is treating the most troublesome symptoms: trialling one medication, seeing if it works, and finding the right dose, then trialling the next one and the next one until things get sufficiently under control.

My predominant subtype is hyperadrenergic, so that’s where I’m going to start. That way I can more easily walk you through the path I took through these playbooks.

The Hyperadrenergic Playbook

Now, the fact that I refer to this as the hyperadrenergic playbook should not imply that everyone who benefits from a beta-blocker or ivabradine is strongly hyperadrenergic; it’s simply that we benefit most from this class of medications, so, like Mar and Raj, I locate these medications here.

The issue in hyperadrenergic POTS proper is too much norepinephrine, one of the catecholamines (stress hormones). Norepinephrine is a hormone that signals the body to do all sorts of things associated with the fight-or-flight response to danger (that lion on the savannah I was referring to in my first post), and for those with this subtype, our bodies make too much of it in response to standing. Standing is the lion! As part of this activation of the sympathetic nervous system (the branch of the autonomic nervous system that prepares us to deal with danger), norepinephrine also signals the heart to beat faster and the blood vessels to constrict, hence the tachycardia (high heart rate) but also especially the often characteristic increase in blood pressure in this subtype.

One key strategy for hyperadrenergic POTS has more to do with reducing sympathetic activation by withdrawing medications that increase it and perhaps choosing other alternatives. Medications frequently used for anxiety and depression, like SSRIs, SNRIs, and NRIs (the N stands for norepinephrine), can make our symptoms worse. Obviously, depression, anxiety, etc. can be debilitating (and sometimes life-threatening) in themselves, so your doctor may strike a compromise and keep you on them if the benefits of these medications outweigh the risks to you.

(As people with the hyperadrenergic subtype in particular are frequently misdiagnosed with anxiety disorders because of our increased physiological arousal, the fact that one of the go-to anxiety treatments we are offered can actually make our symptoms worse is wildly unhelpful. Prior to learning of the existence of POTS, I did a brief trial of Zoloft when I had run out of answers and chalked my symptoms up to maybe depression. It did not work.)

Other medications can also exacerbate this subtype in particular. I had tremendous issues early on with bronchodilators like ventolin (aka albuterol/salbutamol), and the decongestant pseudoephedrine (old Sudafed, which is basically fake adrenaline). I misattributed the shortness of breath caused by my POTS to my recent asthma diagnosis, and got into a terrible spiral of increased bronchodilator use and worsening POTS symptoms. In general, I am wary of sympathomimetics, medications that increase sympathetic nervous system activity. I’ve already got plenty of that, thanks. I don’t need more.

The key pharmacological strategies in the hyperadrenergic POTS playbook are: reduce heart rate, reduce sympathetic activity, and increase parasympathetic activity (the parasympathetic nervous system gently brings you down, like a parachute, into a rest-and-digest state). Key medications in this playbook are:

• Beta blockers (the -olol medications, like propanolol, bisoprolol, and metoprolol) to reduce heart rate and partly reduce the effects of norepinephrine.
• Ivabradine to reduce the heart rate via a different mechanism.
• a₂-adrenergic agonists like clonidine, guanfacine, and methyldopa to block norepinephrine at the source (these are specific to centrally-mediated hyperadrenergic POTS, and not for everyone).
• Pyridostigmine to increase parasympathetic activation.

My trip through this playbook began, as so many do whether hyperadrenergic or not, with beta(-adrenergic) blockers. Because I have some mild asthma, we skipped propanolol and went straight to metoprolol. Metoprolol certainly helped, but I did not like the way it made me feel (kinda flat). I also could not continue on them because I intended to recommence allergy immunotherapy; beta blockers are contraindicated because they block the effectiveness of Epi-pens in the case of anaphylaxis.

My cardiologist then trialled me on ivabradine. This worked well for me. I do not get any side effects, apart from the occasional luminous phenomena, a visual distortion I like to call “sparklevision.” When I get it, it makes it difficult to read and I wouldn’t want to drive during these episodes, but for me it typically goes away in a half an hour or so. Ivabradine remains the foundation of my medication combo.

I next suggested that we trial clonidine; I had known my symptoms were adrenergic for a long time, and something about this medication felt right. Clonidine has been a really great medication for me; I only wish it were available in longer-acting forms here in Canada. The first time I took it — it’s fairly fast acting — I reported that “I feel like fucking sunshine!” My reaction to clonidine has calmed down as my body has gotten used to it, but it definitely helps me not feel agitated all the time and feel a lot weller and more normal.

It’s not uncommon for people with hyperadrenergic POTS to be on ivabradine and one of the a₂-adrenergic agonists together — their effects don’t really overlap, apart from their reduction of tachycardia. Anecdotally, some people with hyperadrenergic POTS also add a beta blocker on an as-needed basis.

This combo was working well, but I still experienced a great deal of fatigue, so we looked at another playbook for options: the hypovolemic playbook.

The Hypovolemic Playbook

The key problem in the hypovolemic subtype of POTS is low blood volume, so the obvious strategy is to increase volume. Most of us, regardless of predominant subtype, are recommended to increase salt and fluids (exercise also helps increase volume), but this is where salt and fluids make the biggest difference.

The key medications for increasing blood volume are:

• Fludrocortisone (in low doses), which helps the body hang onto salt, and therefore hang onto water.
• Desmopressin

It may seem counterintuitive to give someone who tends towards high blood pressure a) additional salt, and b) a medication that helps them hang onto salt, but fludrocortisone was the next medication we trialled. It works well for me, but only at a small dose; otherwise, it does seem to drive up my resting blood pressure.

Adding fludrocortisone had an interesting effect due to my hyperadrenergic POTS: The more active and upright I was able to be because of the fludrocortisone (yay!), the more norepinephrine my body releases (boo!). So I am still homing in on out that balance of pacing and medication that allows me to be as active as possible without triggering hyperadrenergic symptoms.

That’s where my POTS treatment has parked for now, but there’s one more playbook to cover: the neuropathic playbook.

The Neuropathic Playbook

In the neuropathic subtype, the key problem is that there is nerve damage that prevents blood vessels, in the lower extremities and abdomen especially, from constricting enough to push blood back up. The solution is to increase vasoconstriction. This is the rationale behind compression and countermaneuvers (squeezing leg, butt, and ab muscles); these mimic vasoconstriction in the way that they help to push blood back up. Muscle mass in the lower body also helps with this; it’s like having built-in compression gear. I do a lot of strength training that works my leg, butt, and core muscles, and my martial arts training also helps with this.

The key medications for increasing vasoconstriction are therefore:

• Midodrine, the heavy hitter here, and the only medication so far whose use is well supported by evidence.
• Other stimulants are anecdotally reported to help.

Unfortunately, I have no experience with midodrine to share here, as this is not a medication I have tried.

As you can see, there are options. And there are options outside of those I presented that people use every day and that are still being researched to determine their effectiveness for use in POTS.

One more thing: Because the different subtypes have different underlying mechanisms, what makes one person’s POTS better can make another person’s POTS worse. Clonidine really only works for people who are strongly hyperadrenergic; it will make other people feel worse. SSRIs anecdotally help a lot of people with POTS, but can worsen hyperadrenergic POTS symptoms. Beta blockers can make POTS symptoms worse if they mess with the portion of tachycardia that is secondary to hypovolemia or lack of vasoconstriction. That’s why I am reluctant to share notes on which meds I take with people who aren’t expressly hyperadrenergic: Just because my meds have helped me doesn’t mean they will help you at all. POTS treatment is often a matter of throwing spaghetti at the wall to see what sticks; there are few shortcuts.

For more information on medications and treatments that you can share with your medical professionals, our local BC Women’s Complex Chronic Diseases program shares their POTS Clinical Protocol, published in 2018. Some of the meds I mention (mostly the a₂-adrenergic agonists besides clonidine) are not included, but it’s an excellent roadmap if your providers are largely unfamiliar with POTS treatments.