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Postural Tachycardia Syndrome (POTS)
Satish R. Raj
Circulation. 2013;127:2336-2342
doi: 10.1161/CIRCULATIONAHA.112.144501
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CliniCian Update
Postural Tachycardia Syndrome (POTS)
Satish R. Raj, MD, MSCI
Patient O.T. is a 26-year-old white  baroreceptors and triggers a compensa- Figure 1. In young children, a higher 
woman who works in the music 
tory decrease in parasympathetic tone 
HR threshold (≥40 bpm) should be 
industry. She was diagnosed with 
and an increase in sympathetic activa-
used because healthy younger children 
pneumonia and treated with inhalers. 
tion, with a resultant increase in HR 
have a greater orthostatic tachycardia.2 
Shortly afterward, she developed spells 
and systemic vasoconstriction (coun-
There is significant diurnal variability 
of tachycardia. Her episodes of tachy-
tering the initial decline in BP). The 
in the magnitude of orthostatic tachy-
14,26,27
cardia were primarily associated with 
net hemodynamic effect of transition 
cardia3; therefore, postural vital signs 
upright posture. In addition to rapid 
to upright posture is a 10- to 20-bpm 
should be performed in the morning 
palpitations, she complained of light-
increase in HR, a negligible change in 
to optimize diagnostic sensitivity for 
headedness and presyncope on stand-
systolic BP, and a ≈5-mm Hg  increase 
POTS. The orthostatic tachycardia 
ing, intermittent stabbing chest pains 
in diastolic BP. Orthostatic dysregula-
must occur in the absence of other overt 
(typically on standing), mental cloud-
tion occurs when this gravitational reg-
causes of orthostatic tachycardia such 
ing with an inability to concentrate, 
ulatory mechanism does not respond 
as prolonged bed rest, medications that 
severe fatigue, and exercise intoler-
properly. Patients can present with 
impair autonomic regulation (such as 
ance. Orthostatic vital signs recorded 
orthostatic hypotension (seen in auto-
vasodilators, diuretics, antidepressants, 
a supine heart rate (HR) of 73 bpm 
nomic nervous system failure) or with 
or anxiolytic agents), or chronic debili-
with a blood pressure (BP) of 103/72 
orthostatic tachycardia (seen in POTS). 
tating disorders that might cause tachy-
mm Hg. After standing for 1 minute, 
Patients with POTS typically maintain 
cardia (such as dehydration, anemia, or 
her HR increased to 106 bpm with a 
(or even increase) their BP on standing. 
hyperthyroidism).
11
BP of 109/80 mm Hg, and after 5 min-
The cardinal hemodynamic feature in 
Symptoms often include both car-
utes, her HR was 122 bpm with a BP 
POTS is that HR increases excessively 
diac symptoms (rapid palpitations, 
of 118/75 mm Hg. She was diagnosed 
and is associated with multiple symp-
June
lightheadedness, chest discomfort, and 
with postural tachycardia syndrome 
toms on standing that improve with 
dyspnea) and noncardiac symptoms 
(POTS).
recumbence.
(mental clouding [“brain fog”], head-
2013
ache, nausea, tremulousness, blurred 
Upright Posture
Diagnostic Criteria 
or tunneled vision, poor sleep, exercise 
Under normal conditions, the assump-
and Common Clinical 
intolerance, and fatigue). Even activi-
tion of upright posture effects an instan-
Features of POTS
ties of daily living such as bathing or 
taneous shift of ≈500 mL of blood 
POTS is defined (Table 1) as the pres-
doing housework may greatly exacer-
from the thorax to the lower abdomen, 
ence of chronic symptoms of ortho-
bate symptoms, with resultant fatigue. 
buttocks, and legs. There is a second-
static intolerance (at least 6 months) 
This can pose significant limitations 
ary shift of plasma volume (10% to 
accompanied by an increased HR ≥30 
on functional capacity. Although pre-
25%) out of the vasculature and into 
bpm within 10 minutes of assuming an 
syncope and lightheadedness are com-
the interstitial tissue, which decreases 
upright posture and in the absence of 
mon in these patients, only a minority 
venous return to the heart (preload), 
orthostatic hypotension (a decrease in 
(≈30%) actually faint. The chest 
resulting in a transient decline in car-
BP >20/10 mm Hg).1 An example of a 
pains are almost never attributable to 
diac filling and BP. This unloads the 
tilt test in a POTS patient is shown in 
coronary artery obstruction but may 
From the Autonomic Dysfunction Center, Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, 
Nashville, TN.
Correspondence and reprint requests to Satish R. Raj, MD, MSCI, AA3228 Medical Center N, Vanderbilt University, 1161 21st Ave S, Nashville, TN, 
37232-2195. E-mail xxxxxx.xxx@xxxxxxxxxx.xxx
(Circulation. 2013;127:2336-2342.)
© 2013 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org 
DOI: 10.1161/CIRCULATIONAHA.112.144501
2336
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Raj  POTS 
Review  2337
Table 1.  Criteria for the Postural 
abnormalities in nitric oxide activity in 
hyperactivity disorder rating scale, 
Tachycardia Syndrome
the skin of POTS patients.6
POTS patients scored significantly 
worse than healthy control subjects.7 
Heart rate increases ≥30 bpm from supine to 
standing (10 min)
Psychological Profile in POTS
This suggests that the problem in 
Symptoms worsen with standing and improved 
Patients with POTS are sometimes 
POTS may not be with memory per se 
with recumbence
clinically diagnosed as having anxiety 
but with diminished attention.
Symptoms last ≥6 mo
disorders such as panic disorder. When 
assessed with a structured evaluation 
Fatigue, Sleep Problems, and 
Absence of other overt cause of orthostatic 
symptoms or tachycardia (eg, active bleeding, 
for Diagnostic and Statistical Manual 
Quality of Life in POTS
acute dehydration, medications)
(fourth edition, text revision) criteria, 
POTS patients commonly complain 
POTS patients did not have a higher 
of fatigue, unrefreshing sleep, and 
be associated with ECG changes in 
incidence of major depressive disorder, 
daytime sleepiness. When formally 
the inferior leads, particularly when 
anxiety disorders, or substance abuse 
assessed with the Fatigue Visual Ana-
upright.
than the general population.7
log Scale, the Medical Outcomes Study 
The overwhelming majority of 
When assessed with the Beck 
Sleep Survey, and the Epworth Sleepi-
patients with POTS are women (80% 
Anxiety Inventory, patients reported 
ness Scale, POTS patients had more 
to 85%) of child-bearing age (13–50 
elevated anxiety scores (23±10 versus 
sleep problems (Sleep Problems Index: 
years).4 Patients frequently report 
7±8;  P<0.001).7 However, the Beck 
58±18 versus 20±13; P<0.0001) and 
that their symptoms began after acute 
Anxiety Inventory scores both somatic 
excessive daytime sleepiness (10.2±5.7 
stressors such as pregnancy, major 
anxiety and psychological symptoms, 
versus 6.2±3.2; P<0.0001) compared 
surgery, or a presumed viral illness, 
which is a problem because somatic 
with healthy control subjects.8 POTS 
but in others cases, symptoms develop 
symptoms may overlap with hyper-
patients also had higher fatigue levels 
more insidiously. About 80% of female 
adrenergic states (as seen in POTS). 
(7.5±2.0 versus 2.8±2.5; P<0.0001). 
patients report an exacerbation of 
When POTS patients were assessed 
We8 and others9 have documented low 
symptoms around menstruation.5 Many 
with a psychological-based measure 
health-related quality of life in patients 
patients have been codiagnosed with 
of anxiety (Anxiety Sensitivity Index), 
with POTS. Using the Short Form-36, 
irritable bowel syndrome; some have 
there was a trend toward less anxiety in 
Benrud-Larssen et al9 reported that 
hypermobile joints; and some have 
the patients than in the general popu-
physical and mental composite scores 
abnormal sudomotor regulation.
lation (15±10 versus 19±9; P=0.063).7 
for POTS patients were comparable 
A striking physical feature in ≈50% 
It is possible that some of the anxiety 
to those for patients with congestive 
of patients with POTS is a dependent 
attributed to patients with POTS might 
heart failure. It is noteworthy that of 
acrocyanosis (Figure 2). These patients 
be a result of a misinterpretation of 
the 8 domains specifically addressed 
experience a dark red-blue discol-
their physical symptoms.
by the Short Form-36, the only domain 
oration of their legs (feet to above 
Many POTS patients complain of 
in which POTS patients did not fare 
knees), which are cold to the touch. 
memory problems. In formal test-
worse than the control group was men-
The reasons underlying this phenom-
ing with the inattention score from 
tal health.9
enon are not clear but may relate to 
the Connors adult attention-deficit/
The subjects in the aforementioned 
sleep study also completed the RAND-
36, a validated general health-related 
quality-of-life tool. There was a strong 
correlation between the RAND-36 
physical health composite scores and 
the Sleep Problems Index (R2=0.53, 
P<0.0001), with >50% of the variance 
in physical health explained by the 
variance in sleep quality.8
Pathophysiology of POTS
POTS is a syndrome and not a disease. 
Figure 1. Heart rate (HR) and blood pressure (BP) with upright tilt in postural tachycardia 
Many disorders with the common key 
syndrome (POTS). HR, BP, and tilt table angle are shown for a representative patient 
with POTS (left) and for a healthy subject (right) during a 30-minute head-up tilt test. 
clinical presentation of orthostatic 
With tilt, HR immediately increases in POTS and peaks at >170 bpm before the end 
tachycardia have been described. Much 
of the tilt, whereas the HR of the healthy subject rises to just over 100 bpm. BP was 
has been learned about specific features 
largely unchanged in the POTS patient. Figure reprinted with permission from Raj SR. 
or subtypes within POTS, although a 
The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management. 
Indian Pacing Electrophysiol J. 2006;6:84–99.1
simple test to categorize the individual 
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2338  Circulation  June 11, 2013
patient remains elusive. Some common 
POTS phenotypes are described here.
Neuropathic POTS
Although many POTS patients have 
high plasma norepinephrine levels, it 
would seem paradoxical that an auto-
nomic neuropathy is proposed as an 
underlying process. Yet some patients 
have a form of dysautonomia, with 
preferential denervation of sympathetic 
nerves from the lower limbs. Jacob et 
al10 showed that some patients with 
POTS had less norepinephrine release 
(less sympathetic activation) in their 
lower extremities.
Figure 2. Dependent acrocyanosis in postural tachycardia syndrome (POTS). A striking 
physical feature in POTS is the gross change in dependent skin color that can occur 
Central Hyperadrenergic POTS
with standing. Shown are the legs of a healthy subject (left) and a patient with POTS 
Many patients with POTS have ele-
(right) after standing for 5 minutes. The patient with POTS (right) has significant dark 
vated levels of plasma norepinephrine, 
red mottling of her legs extending up to the knees while standing, whereas the healthy 
subject does not have a similar discoloration. Figure reprinted with permission from 
suggestive of a hyperadrenergic state. 
Raj SR. The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & 
This is most commonly secondary to 
management. Indian Pacing Electrophysiol J. 2006;6:84–99.1
a partial dysautonomia or hypovole-
mia. In a small subgroup of patients, 
Although functional norepinephrine 
diuresis, and gastrointestinal symp-
the primary underlying problem seems 
transporter mutations might be infre-
toms such as diarrhea, nausea, and 
to be excessive sympathetic discharge. 
quent, many antidepressant and atten-
vomiting. These patients often have a 
These patients often have extremely 
tion deficit medications work at least in 
hyperadrenergic response to posture, 
high levels of upright plasma norepi-
part through inhibition of norepineph-
with both orthostatic tachycardia and 
nephrine (>1000 pg/mL and occasion-
rine transporter. This includes traditional 
hypertension. There are many triggers 
ally >2000 pg/mL, with an upper limit 
drugs such as tricyclic antidepressants, 
for the flushing, including prolonged 
of normal of 475 pg/mL in our clini-
serotonin-norepinephrine reuptake  standing, exercise, premenstrual cycle, 
cal laboratory). Plasma metanephrines 
inhibitors (eg, duloxetine, venlafaxine, 
meals, and sexual intercourse.
will exclude a pheochromocytoma. 
or milnacipran), or purer norepineph-
Centrally acting agents to decrease 
This subgroup of patients sometimes 
rine transporter inhibitors (eg, atomox-
the sympathetic nervous system dis-
have large increases in BP on standing, 
etine or reboxetine). Pharmacological 
charge (eg, methyldopa or cloni-
indicating that baroreflex buffering is 
norepinephrine transporter inhibition 
dine) may prove effective, although 
somehow impaired. Therapy in these 
can recreate an orthostatic tachycardia 
β-blockers may actually trigger mast 
patients targets a decrease in sympa-
phenotype in susceptible healthy vol-
cell degranulation and worsen symp-
thetic tone both centrally and periph-
unteer subjects.12 POTS patients might 
toms. Treatment can also target mast 
erally. Central sympatholytics such as 
have less tachycardia reserve and be 
cell mediators, with a combination of 
methyldopa or clonidine may be used. 
more susceptible to exaggerated tachy-
antihistamines (H  and H  antagonists) 
1
2
Peripheral  β-adrenergic blockade may 
cardia with these medications.
and possible use of nonsteroidal agents 
be better tolerated by these patients than 
in refractory cases.
by those with primary hypovolemia.
Mast Cell Activation
Some patients with POTS present 
Hypovolemia and Blood Volume 
Norepinephrine Transporter 
with episodic flushing associated 
Regulation
Deficiency and Blockers
with surges in tachycardia and have 
Many, but not all, patients with POTS 
A specific genetic abnormality has 
coexistent mast cell activation. They 
have low blood volumes.14 Using the 
been identified in a kindred with hyper-
may have abnormal increases in urine 
131I-labeled human serum albumin 
adrenergic POTS.11 These individuals 
methylhistamine (the primary urinary 
method, we found that POTS patients 
have a single point mutation causing 
metabolite of histamine),13 which 
had a plasma volume deficit of almost 
loss of function in the norepinephrine 
should ideally be measured from a 
13%.14
transporter. The resultant diminished 
4-hour sample at the time of a flush-
The renin-angiotensin-aldosterone 
norepinephrine clearance leads to a 
ing episode (not a 24-hour sample). 
system plays a key role in the neuro-
hyperadrenergic state in response sym-
This can be associated with dyspnea, 
hormonal regulation of plasma volume 
pathetic nerve activation.
headache, lightheadedness, excessive 
in humans. Plasma renin activity and 
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Raj  POTS 
Review  2339
angiotensin II would be expected to 
The tachycardia in POTS patients 
immediately after a severe flushing 
increase in response to hypovolemia 
should originate from the sinus node. 
spell.
to promote blood volume expansion. 
An ECG should be routinely performed 
Angiotensin II promotes sodium and 
to exclude the presence of an accessory 
Nonpharmacological 
water retention indirectly by stimulat-
bypass tract or other abnormalities of 
Treatment of POTS
ing aldosterone secretion.
cardiac conduction. A Holter moni-
No therapy is uniformly successful, 
Patients with orthostatic tachycar-
tor might prove useful to exclude a 
and combinations of approaches are 
dia who were also hypovolemic have 
reentrant tachyarrhythmia, especially 
often needed. Efforts should initially 
inappropriately low levels of standing 
if the tachycardia is paroxysmal with 
focus on treating any reversible causes. 
plasma renin activity and aldosterone 
a sudden onset and offset. The physi-
If a patient has had a bout of prolonged 
compared with normovolemic sub-
cian must determine that cardiac left 
bed rest, his or her symptoms should 
jects.14 One would have expected a 
ventricular function is normal, using an 
gradually improve as the patient recon-
compensatory increase in both plasma 
echocardiogram if needed. Peripartum 
ditions to upright posture. Treatment 
renin activity and aldosterone resulting 
cardiomyopathy, for example, can 
should be optimized for any chronic 
from the hypovolemia in these patients, 
present in a manner similar to POTS.
disease that is present. Radiofrequency 
and these low levels are a paradox that 
We often measure plasma norepi-
ablation may be needed to treat reen-
remains unexplained.
nephrine levels in both a supine and a 
trant supraventricular tachyarrhyth-
More recently, we15 have reported 
standing position (at least 10 minutes 
mia, but radiofrequency sinus node 
high levels of angiotensin II levels 
in each position before blood sam-
modification for the sinus tachycardia 
circulating in POTS patients without 
pling). The supine norepinephrine 
a commensurate increase in angio-
of POTS is not recommended because 
is often within the normal range in 
tensin(1–7), suggesting that POTS 
it often makes the patient’s symptoms 
POTS patients, whereas the upright 
patients might have decreased angio-
worse (and occasionally pacemaker 
norepinephrine is frequently elevated 
tensin II metabolism. The aldosterone 
dependent). Specific therapies are sum-
(>600 pg/mL), reflecting the exagger-
level is lower per unit of angiotensin II 
ated neural sympathetic tone present in 
marized in Table 2.
in POTS patients.15 These data suggest 
these patients while upright.
Patient education is important. 
that abnormalities in the renin-angio-
Autonomic reflexes are usually 
Patients with POTS should avoid 
tensin-aldosterone axis might have a 
intact on formal tests of autonomic ner-
aggravating factors such as dehydra-
role in the pathophysiology of POTS 
vous system function. POTS patients 
tion and extreme heat. To ensure ade-
by contributing to hypovolemia and 
often have preserved vagal function 
quate hydration, we ask our patients to 
impaired sodium retention.
(as reflected by their sinus arrhythmia 
consume 8 to 10 cups of water daily 
ratio in response to deep breathing) 
and to increase their sodium intake 
Investigation of POTS
and a vigorous pressor response to the 
to up to 8 to 10 g/d. If this cannot be 
The evaluation of a patient with POTS 
Valsalva maneuver, with an exagger-
accomplished with dietary modifica-
starts with a detailed history and 
ated BP recovery and overshoot both 
tion, supplemental NaCl tablets (with 
physical examination. POTS can be 
before and after release.13 Given the 
meals) can be used. Elastic support 
confused with pheochromocytoma 
complaints of exercise intolerance, for-
hose can help to minimize the degree 
because of the paroxysms of hyper-
mal cardiopulmonary exercise testing 
of peripheral venous pooling and to 
adrenergic symptoms (eg, palpitations 
can be useful for objective documen-
enhance venous return. We recom-
and lightheadedness). Patients with 
tation of exercise capacity; it can also 
mend panty hose (waist high)–style 
pheochromocytoma are more likely to 
be used serially to quantify functional 
stockings with 30 to 40 mm Hg of 
have these symptoms while lying down 
capacity over time.
pressure.
than POTS patients. The diagnosis of 
The blood volume is low in many 
Acute blood volume expansion will 
pheochromocytoma is made by assess-
patients with POTS.14 This can be 
over the short-term improve symptoms 
ment of plasma or urinary metaneph-
objectively assessed with nuclear 
and control HR. Jacob et al16 found 
rines. We order a complete blood count 
medicine tests to directly measure 
that 1 L of normal saline infused intra-
and an electrolyte panel to exclude 
either the plasma volume or the red 
venously over 1 hour normalized the 
severe anemia or gross electrolyte dis-
cell volume. Some patients with POTS 
orthostatic tachycardia (before, 33±5 
turbances. Some physicians specializ-
have coexistent complaints of episodic 
bpm; after, 15±3 bpm). Acutely, this 
ing in POTS will also assess vitamin 
flushing, and a minority of these cases 
treatment is more effective at HR con-
B  levels, iron indexes, and serologi-
result from an associated mast cell 
trol than other medications. Although 
12
cal markers for celiac disease, although 
activation disorder.13 This can be diag-
this can be a very effective emergency 
there are insufficient data supporting 
nosed by measuring methylhistamine 
therapy, it is not a practical day-to-day 
the routine use of these tests.
levels from a 4-hour urine sample 
approach.
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2340  Circulation  June 11, 2013
Table 2.  Treatments for the Postural Tachycardia Syndrome
Therapy
Comments
Exercise program
Primarily aerobic with some leg-based resistance exercises
Initially avoid upright exercises and focus on rowing machines, swimming, and recumbent 
cycles
Augment blood volume/venous return
   Increase water intake
Target, 8–10 cups/d (2–2.5 L/d)
   Increase NaCl intake by diet or tablets
Target, 8–10 g/d; can add in NaCl 1-g tablets as needed
   Intravenous saline (immediate effect)
1 L over 1–2 h IV; short-term emergency treatment
   Panty hose–style compression stockings
30–40 mm Hg counterpressure
   Withdraw OCP with drosperinone
Drosperinone is a spironolactone analog that could worsen hypovolemia
   Fludrocortisone
0.1–0.2 mg/d orally; watch for hypokalemia
   Desmopressin (DDAVP)
0.2 mg orally 1 time for occasional use
Could cause hyponatremia with regular use
Hemodynamic agents
   Withdraw drugs that block the norepinephrine transporter
These drugs can increase peripheral sympathetic tone and worsen tachycardia
These include tricyclic antidepressants, ADHD drugs, and SNRI antidepressants
   Propranolol
10–20 mg orally 3–4 times a day
Low doses to take the edge off of tachycardia are more effective than higher doses
   Pyridostigmine
30–60 mg orally 3 times a day
May increase parasympathetic tone for augmented HR control
Can increase GI motility, which can be major source of intolerance
   Midodrine
5–10 mg orally every 4 h in 3 doses (not close to bedtime)
Side effects include goose bumps, scalp itch, hypertension and urinary retention
Other
   Modafinil
100 mg orally twice a day
Approved for various sleep problems but may help with mental alertness and 
concentration in patients
ADHD indicates attention deficit/hyperactivity disorder; GI, gastrointestinal; NaCl, table salt; OCP, oral contraceptive pill; and SNRI, serotonin-norepinephrine reuptake 
inhibitor.
Exercise
Pharmacological 
recommend that patients be switched 
Exercise has routinely been recom-
Treatment of POTS
to an oral contraceptive that uses a dif-
mended as part of the treatment regi-
The Food and Drug Administration 
ferent progestin.
men for many years. Unfortunately, 
has not approved any medications for 
In patients in whom the presence 
POTS patients report feeling debili-
the treatment of POTS. Therefore, all 
of hypovolemia is either known or 
tated for days after exertion, limiting 
agents used for this disorder are off 
strongly suspected, fludrocortisone 
compliance. Anecdotally, patients who 
label. Furthermore, all trials have been 
(aldosterone analog) is often used. 
exercise seem to have a better long-
of a short duration, with none tested in 
Through enhanced sodium retention, 
term prognosis, but it is not certain if 
a long-term, properly powered, ran-
it should expand the plasma volume. 
Adverse effects can include hypokale-
this is a result of the exercise or of their 
domized, clinical trial.
mia, worsening headaches, acne, and 
ability to exercise. Fu et al
The initial pharmacological 
17 recently 
approach is to withdraw medications 
fluid retention with edema. Another 
administered a structured 3-month 
that might be predisposing to tachycar-
volume-expanding agent that may be 
exercise program to 19 patients with 
dia (such as diuretics, vasodilators, and 
helpful for short-term use is desmo-
POTS. This relatively short interven-
norepinephrine transporter blockers). 
pressin (DDAVP).18 This agent causes 
tion reduced orthostatic tachycardia 
Given their demographics, many POTS 
the kidney to retain free water but not 
and improved quality of life. Physi-
patients take oral contraceptives. Some 
sodium. Potential side effects include 
ological parameters such as blood vol-
agents (eg, Yaz or Yasmin) include dro-
hyponatremia, edema, and headache. 
ume, stroke volume, and left ventricular 
sperinone as the progestin, which is a 
We have allowed patients to use this 
mass all improved over the 3 months. 
spironolactone analog. Given that inap-
only less often than 1 time per week 
This study elegantly showed that exer-
propriately low aldosterone and low 
in a pill in the pocket manner for spe-
cise, not just the ability to exercise, is 
blood volume have been identified as 
cial events. Although DDAVP is safely 
important in this population.
a problem in some POTS patients, we 
used in children for enuresis, we have 
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Raj  POTS 
Review  2341
been concerned about the risk of hypo-
times a day (eventually switched to a 
continue to work because of her brain 
natremia in patients told to drink free 
long-acting patch) can stabilize HR and 
fog.
water copiously.
BP in patients with high sympathetic 
Midodrine is a peripheral α-1 ago-
nervous system activity. Methyldopa 
Acknowledgments
nist that serves as a vasoconstrictor. It 
125 to 250 mg orally 2 times a day is 
I thank David Robertson, MD, for his 
might be most useful in patients with 
a false neurotransmitter that is some-
thoughtful review of this manuscript.
neuropathic POTS, which can be asso-
times better tolerated because of its 
ciated with a failure of vascular resis-
longer half-life. Unfortunately, both 
Sources of Funding
tance. Jacob et al16 have documented 
drugs can cause drowsiness and fatigue 
This work was supported in part by National 
that midodrine reduces orthostatic 
and worsen the mental clouding of 
Institutes of Health grants P01 HL56693, 
tachycardia, but this effect is more 
some patients.
R01 HL102387, and UL1 TR000445.
modest than that of intravenous saline. 
Many patients are also greatly trou-
Midodrine can cause goose bumps, 
bled by mental clouding or troubles 
Disclosures
scalp tingling, or headaches, which can 
concentrating. Modafinil, a stimulant 
None.
limit its tolerability.
with a mechanism that is not yet clear, 
β-Adrenergic blockers are com-
can improve alertness in some patients 
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