Treatment of Orthostatic and Postprandial Hypotension

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Treatment of orthostatic and postprandial hypotension

Author: Horacio Kaufmann, MD
Section Editors: Michael J Aminoff, MD, DSc, Peter Kowey, MD, FACC, FAHA, FHRS
Deputy Editor: Janet L Wilterdink, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2020. | This topic last updated: Oct 25, 2018.
INTRODUCTION
When autonomic reflexes are impaired or intravascular volume is markedly depleted, a significant
reduction in blood pressure occurs upon standing (ie, orthostatic hypotension). Orthostatic
hypotension can be asymptomatic or symptomatic, causing lightheadedness, dizziness or
syncope, and even angina due to postural myocardial ischemia.
Symptomatic falls in blood pressure after standing or eating are a frequent clinical problem. The
prevalence of orthostatic hypotension varies from 5 to 30 percent in different reports. Many
disorders can cause orthostatic hypotension, which can also be a symptom of acute or chronic
volume depletion. A related problem, postprandial hypotension (a fall in blood pressure occurring
15 to 90 minutes after meals) is also common in older patients. Orthostatic hypotension can be a
disabling condition and is also a risk factor for cardiovascular and all-cause mortality, as well as
falls with attendant morbidity.
This topic will review the treatment of chronic orthostatic and postprandial hypotension due to
impaired cardiovascular autonomic reflexes, also referred to as neurogenic orthostatic
hypotension [1]. The patient with acute orthostatic hypotension due to volume depletion should be
treated with volume replacement.
The causes and evaluation of orthostatic hypotension are discussed separately. Postural
tachycardia syndrome (POTS) is also discussed separately. (See "Mechanisms, causes, and
evaluation of orthostatic hypotension" and "Postural tachycardia syndrome".)
TREATMENT GOALS
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In general, treatment is titrated towards symptomatic relief rather than correction of measured
orthostatic hypotension. Asymptomatic orthostatic hypotension is common and of uncertain clinical
relevance [2,3]. We do not treat asymptomatic hypotension.
NONPHARMACOLOGIC MEASURES
The following sections on therapy are directed toward the patient with chronic orthostatic
hypotension due to autonomic dysfunction (ie, neurogenic orthostatic hypotension). The patient
with acute orthostatic hypotension due to volume depletion should be treated with volume
replacement.
Nonpharmacologic measures are an important first-line therapy for neurogenic orthostatic

hypotension. These include removal of offending agents, patient education, physical and dietary
interventions, and avoidance of precipitating factors. While limited numbers of randomized studies
to evaluate efficacy exist, clinical experience suggests benefit of nonpharmacologic therapy while
avoiding medication side effects [4]. All of the following measures should be implemented, when
possible.
Discontinue exacerbating medications — Recognition and discontinuation of drugs that cause

orthostatic hypotension is the first management step. The most common offending agents are
diuretics, antihypertensive agents (primarily sympathetic blockers), antianginal drugs (nitrates),
alpha-adrenergic antagonists, and antidepressants (table 1). Lowering the dose or discontinuing
the medication when possible may be all that is required to correct orthostatic hypotension.
Modification of daily activities — Patient education is essential for the management of chronic
orthostatic hypotension. Throughout the day, patients are subject to a number of orthostatic
demands for which there are simple and effective countermeasures. As a result, emphasizing
practical management principles is paramount. These measures include [5]:
● Arising slowly, in stages, from supine to seated to standing. This maneuver is most important
in the morning, when orthostatic tolerance is lowest.
● Avoiding straining, violent coughing, or walking in very hot weather, as these activities reduce
venous return and worsen orthostatic hypotension. If necessary, treat constipation with stool
softeners and diet changes, and use cough suppressants when these triggers are
problematic.
● Maintaining adequate hydration and avoiding overheating.
● Raising the head of the bed 10 to 20 degrees to decrease renal perfusion, thereby activating
the renin-angiotensin-aldosterone system (in patients who are still able to) and decreasing
nocturnal diuresis, which can be pronounced in these patients. These changes relieve

orthostatic hypotension by expanding extracellular fluid volume and may reduce end-organ
damage by reducing supine hypertension.
Only small case series and clinical experience support the efficacy of this intervention, but its
effect in patients with autonomic failure can be dramatic [6]. In one series of nine older
inpatients with orthostatic hypotension, 6 inches of head-of-bed elevation during sleep was
associated with higher blood pressure and improved mobility after one week of treatment [7].
A follow-up study by the same investigators found that this same intervention in 100
community-dwelling patients had no effect on symptoms or hemodynamic parameters after
six weeks [8].
● Exercise may be beneficial when cardiovascular deconditioning rather than chronic autonomic
failure is the cause of orthostatic hypotension. As an example, a small study of five older adult
patients in whom tilt-table testing at baseline resulted in symptoms showed that an exercise
regimen consisting of walking or climbing stairs for 30 to 45 minutes per day three times per
week for six months resulted in symptom disappearance during a repeat tilt-table test [9].
● Modifying meals by reducing high glycemic-index carbohydrate content can be helpful,

especially when symptoms appear to occur in association with eating. (See 'Modification of
meals' below.)
Compression stockings and abdominal binders
● The use of custom-fitted elastic stockings permits the application of graded pressure to the
lower extremities and lower abdomen, thereby minimizing peripheral blood pooling. It is
essential that such stockings extend to the waist since most peripheral pooling occurs in the
splanchnic circulation. These stockings are poorly tolerated by many patients, particularly
those with painful peripheral neuropathies or motor dysfunction and those living in hot
climates. They are difficult to take on and off. Compression stockings may be contraindicated
in patients with evidence of leg ischemia due to peripheral vascular disease, or extensive skin
lesions on their lower extremities. (See "Compression therapy for the treatment of chronic
venous insufficiency", section on 'Contraindications'.)
One report of 10 patients found that compression stockings in patients with orthostatic
hypotension and a history of falls reduced the average degree of orthostasis in the group as a
whole and abolished orthostatic dizziness in seven [10]. In a crossover study of 21 patients,
use of compression bandages was associated with reduced orthostatic blood pressure
decrease and symptoms compared with control [11].
● Abdominal binders ameliorate the orthostatic blood pressure fall in some patients with
orthostatic hypotension and may be better tolerated than compression stockings [4,12,13]. In
a crossover study of 15 patients with Parkinson disease and orthostatic hypotension, use of
an elastic abdominal binder reduced blood pressure fall on head-up tilt and, in a four-week
open-label follow-up, improved symptoms of orthostatic hypotension as assessed by

questionnaire [14]. An automated inflatable abdominal binder that provides sustained servo-
controlled venous compression (40 mmHg) and can be activated only on standing showed
similar symptomatic improvement to midodrine in 19 patients with orthostatic hypotension due
to autonomic failure [15]. Compliance may be a problem.
Physical maneuvers — Specific physical maneuvers appear to be helpful in some patients [4,5]:
● One maneuver that may be effective is tensing the legs by crossing them while actively
standing on both legs. In one series of seven patients with autonomic neuropathy, this
procedure raised the cardiac output by 16 percent and the systemic blood pressure by 13
percent [16,17]. Without leg-crossing, five of the patients reported dizziness within 10 minutes
of standing up; leg-crossing allowed all to stand for 10 minutes or more [16]. Another study
also found that tensing lower body muscles in the legs, buttocks, and abdomen before arising
from a squat position blunted the hypotensive response and clinical symptoms in a series of
13 patients with orthostatic hypotension [17,18].
● Respiratory maneuvers are under investigation as a means of treating orthostatic hypotension

[19]. Increased negative inspiratory intrathoracic pressure may reduce orthostatic hypotension
by augmenting venous return. Techniques such as inspiration through pursed lips, inspiratory
sniffing, and use of an external device causing selective inspiratory obstruction were shown in
10 patients to improve standing blood pressure comparable to leg muscle-tensing.
Hyperventilation should be avoided, as this lowers blood pressure in patients with autonomic
failure.
Increased salt and water intake — The reduction in central blood volume associated with
autonomic insufficiency (due to increased urinary sodium and water excretion) can be attenuated
by increasing sodium and water intake [20-22].
In a study of 11 patients with severe orthostatic hypotension due to autonomic failure, blood
pressure increased significantly after drinking 480 mL of tap water in less than five minutes from
83±6/53±3.4 mmHg at baseline, to 114±30/66±18 mmHg 35 minutes later [20]. After a meal, blood
pressure declined less in patients who drank water during the meal than in patients who did not.
Another study found that water-drinking prior to supine exercise improved orthostatic tolerance
post-exercise [22].
The effect of water is greatest in the hour after ingestion. In addition to drinking water during meals
and before exercise, some clinicians advise keeping a pitcher of water at the bedside and drinking
rapidly before getting out of bed in the morning [5]. A target daily ingestion of 1.5 to 3 L per day is
recommended by some clinicians [23-25].
High sodium-containing foods or salt tablets also may be prescribed. While the optimal dose will
vary among patients, some have suggested a target dose of 6 to 10 g/day of sodium, or a target
urinary sodium level of 150 to 200 mEq [23-26].
Modification of meals — Patients with autonomic failure and even normal older adults are
susceptible to significant falls in blood pressure after meals [27,28]. Postprandial hypotension can
be minimized by [4,27]:
● Avoiding large meals

● Ingesting meals low in carbohydrate
● Avoiding alcohol intake
● Drinking water with meals
● Avoiding activities or sudden standing immediately after eating
PHARMACOTHERAPY
Nonpharmacologic measures are often insufficient to prevent symptoms of orthostatic

hypotension, particularly in patients with moderate to severe disease. Such patients often need
pharmacologic intervention. Two drugs are approved by the US Food and Drug Administration
(FDA) for the treatment of symptomatic neurogenic orthostatic hypotension: the alpha-adrenergic
agonist midodrine and the norepinephrine precursor droxidopa [29]. Numerous other agents from
diverse pharmacologic groups have been utilized in small trials (table 2), but there is limited
evidence to support their use [30,31]. Fludrocortisone, a synthetic mineralocorticoid, which is not
specifically approved by the FDA for the treatment of neurogenic orthostatic hypotension, is widely
used but can lead to sustained hypertension in the supine position.
Step-wise approach and monitoring — Nonpharmacologic measures should be maximized prior

to starting and must be continued after initiating pharmacotherapy. A step-wise approach to drug
treatment that starts with fludrocortisone to induce volume expansion is frequently used, but this
approach is not always ideal, as fludrocortisone has significant long-term side effects. A
reasonable alternative is using vasoconstrictor agents, either midodrine or droxidopa, as initial
pharmacotherapy after volume expansion has been achieved by nonpharmacologic measures.
The therapeutic goal is to ameliorate symptoms while avoiding side effects. Normotension cannot
be perfectly restored. It is important to titrate therapy according to symptoms rather than blood
pressure values.
Patients taking medications for orthostatic hypotension should be taught how to measure their
blood pressure and should provide to the clinician, for monitoring, a series of blood pressure
recordings taken over several days, including when supine, sitting, and standing upon awakening;
before and one hour after lunch; and before retiring to bed [32]. These home readings are useful
for safety (supine hypertension) and efficacy monitoring. The use of ambulatory blood pressure
monitoring can assist to personalize pharmacologic treatment [33].

Initial therapy
Fludrocortisone — Fludrocortisone acetate (9-alpha-fluorohydrocortisone), a synthetic

mineralocorticoid, is commonly used for the treatment of orthostatic hypotension in patients whose
symptoms are not adequately controlled using nonpharmacologic measures [34]. The principal
mode of action of fludrocortisone is an increase in blood volume. Enhanced sensitivity of blood
vessels to circulating catecholamines [35] and enhanced norepinephrine release from sympathetic
neurons are also suggested. A pressor effect of fludrocortisone tends to persist due to increased
peripheral vascular resistance [36].
Treatment with fludrocortisone acetate is initiated at a dose of 0.1 mg per day, administered in the
morning, which can eventually be increased up to 0.3 mg per day; little benefit is obtained by dose
increase beyond 0.2 mg per day, however, while side effects increase significantly. Increments
should not occur more rapidly than weekly.
Patients treated with fludrocortisone must be carefully monitored for the development of edema or
worsening seated or supine hypertension, which may necessitate discontinuation or dose
reduction. Patients taking fludrocortisone should be instructed in monitoring their own blood
pressure recording and should provide to the clinician, for monitoring, a series of blood pressure
recordings taken over several days including when supine, sitting, and standing upon awakening;
before and one hour after lunch; and before retiring to bed [32].
Potassium supplementation is usually required, particularly when higher doses of fludrocortisone

are used. Potassium levels should be checked before starting treatment and within a week or two
of dose adjustment.
Therapy with fludrocortisone acetate may be limited by supine hypertension resulting from the
increase in peripheral vascular resistance [36] (see 'Supine hypertension' below). Other common
side effects include hypokalemia, ankle edema, and congestive heart failure. Edema is generally
not a major problem in the absence of some other sodium-retaining state (see "Pathophysiology
and clinical features of primary aldosteronism"). However, many older patients with autonomic
dysfunction do have concurrent conditions that promote edema.
While fludrocortisone is well tolerated by most patients with chronic autonomic failure,
discontinuation of therapy due to side effects is common. In one study of 64 patients with
orthostatic hypotension, one-third stopped taking fludrocortisone within six months due primarily to
worsening supine hypertension, edema, and congestive heart failure [37].
Sympathomimetic agents — Two sympathomimetic pressor agents are approved by the FDA
for the treatment of neurogenic orthostatic hypotension: the alpha-1-adrenergic agonist midodrine
and the norepinephrine precursor droxidopa. Pressor agents may be used in combination with
fludrocortisone or alone as first pharmacotherapy in those unable or unwilling to tolerate

fludrocortisone acetate side effects. No direct comparisons have been performed between
midodrine and droxidopa.
Other direct and indirect sympathomimetic agents, including ephedrine and pseudoephedrine,
as well as methylphenidate and dextroamphetamine sulphate [38-40], are no longer used in
the treatment of neurogenic orthostatic hypotension because of lack of efficacy or intolerable
central nervous system (CNS) side effects. The effectiveness of sympathomimetic agents is
probably dependent upon the increase in alpha-adrenergic receptor number and affinity, and
the reduction in baroreflex modulation that accompanies autonomic failure [38].
Combining fludrocortisone with an alpha agonist can have synergistic effects and allow for lower
dose of both agents [41,42].
Midodrine — The peripheral selective alpha-1-adrenergic agonist midodrine was the first
drug specifically approved by the FDA for the treatment of orthostatic hypotension; midodrine does
not cross the blood-brain barrier and has a pressor effect due to both arterial and venous
constriction. The efficacy of midodrine in the treatment of orthostatic hypotension has been
suggested in some open-label and double-blind studies [41-45]. Systematic reviews have
concluded that the available data warranted only low confidence that midodrine improves
symptoms in patients with orthostatic hypotension, in part because most studies were designed to
assess an effect on blood pressure and not on symptoms [45,46].
Midodrine, the prodrug, is activated to desglymidodrine, the active alpha agonist. Midodrine is
rapidly absorbed from the gastrointestinal tract and reaches a peak plasma concentration in 20 to
40 minutes; the plasma half-life is 30 minutes.
Since patient sensitivity to this agent varies, the dose should be titrated from 2.5 to 10 mg three
times a day. The maximum dose should not exceed 40 mg/day. Patients should not take midodrine
within four to five hours of bedtime in order to limit supine hypertension. (See 'Supine
hypertension' below.)
Midodrine should not be used in patients with severe heart disease, uncontrolled hypertension, or
urinary retention. Supine hypertension, which occurs both as a consequence of baroreceptor
denervation (even in untreated patients with autonomic failure) and as a side effect of
antihypotensive treatment, often limits therapeutic intervention. Other potential side effects include
pilomotor reactions, pruritus, supine hypertension, gastrointestinal complaints, and urinary
retention [45]. The sympathomimetic side effects, such as anxiety, tremulousness, and
tachycardia, that accompany the use of adrenergic agents that cross the blood-brain barrier do not
occur with midodrine.
Droxidopa — L-dihydroxyphenylserine (DOPS, droxidopa) is a synthetic amino acid,

identical to levodopa but with an added hydroxyl group. After oral administration, droxidopa is
decarboxylated to norepinephrine, the naturally occurring sympathetic neurotransmitter, by the
ubiquitous L-amino acid decarboxylase. The crucial role of norepinephrine in the maintenance of
upright blood pressure and the successful implementation of precursor therapy for Parkinson
disease provide the rationale for the use of this agent to treat neurogenic orthostatic hypotension.
Since the conversion of droxidopa to norepinephrine bypasses the dopamine beta-hydroxylation

step of catecholamine synthesis, droxidopa is the ideal therapeutic agent for patients with
dopamine beta-hydroxylase deficiency; such individuals are unable to synthesize norepinephrine
and epinephrine in the central and peripheral nervous system. Droxidopa also showed benefit in
patients with familial amyloid polyneuropathy [47,48].
Droxidopa dose titration starts at 100 mg and escalates to 600 mg three times per day. Patients
should not take droxidopa within four to five hours of bedtime in order to limit supine hypertension.
(See 'Supine hypertension' below.)
Four clinical trials including 485 patients have evaluated the efficacy of droxidopa in orthostatic
hypotension [47-51]. In these trials, 246 patients received droxidopa and 239 received placebo. In
the aggregate, patients receiving droxidopa had improved symptom scores and increased upright
systolic blood pressure compared with patients who received placebo [51,52]. However, these
trials had limited follow-up of only two to six weeks. Further study to show persistence of efficacy
during chronic use is required.
Droxidopa is approved by the FDA for the treatment of symptomatic neurogenic orthostatic
hypotension associated with Parkinson disease, multiple system atrophy, pure autonomic failure,
and nondiabetic autonomic neuropathy, with a boxed warning regarding the potential for supine
hypertension. However, indirect comparisons suggest that the risk of supine hypertension appears
to be lower with droxidopa than midodrine [53]. (See 'Supine hypertension' below.)
The mechanism of action of droxidopa is not fully understood. After droxidopa administration,
norepinephrine production occurs in neuronal and non-neuronal tissues. Patients with neurogenic
orthostatic hypotension and extensive degeneration of sympathetic neurons (such as those with
pure autonomic failure, Parkinson disease, or dementia with Lewy bodies) retain the ability to
convert droxidopa into norepinephrine and thereby increase their blood pressure. Droxidopa may
also convert into norepinephrine within sympathetic terminals, and the newly synthesized
norepinephrine is then released as a neurotransmitter on activation of sympathetic neurons. The
pressor response to droxidopa is more pronounced in patients with lower plasma concentration of
norepinephrine, a surrogate marker of sympathetic innervation and adrenergic denervation
supersensitivity [54].
Supplementary agents — Erythropoietin, caffeine, pyridostigmine, and nonsteroidal

antiinflammatory drugs (NSAIDs) have been proposed in combination therapy with first- or
second-line agents in patients with persistent symptoms. Evidence of their efficacy is very limited.

Erythropoietin — Recombinant human erythropoietin increases standing blood pressure and

improves orthostatic tolerance in patients with the anemia that often occurs in autonomic failure
[55,56]. A trial of erythropoietin should be used as a first line of treatment in all patients with
orthostatic hypotension and anemia who have low serum erythropoietin concentrations.
Recombinant human erythropoietin, epoetin alpha, is administered subcutaneously or

intravenously at doses between 25 to 75 units/kg three times a week until a hematocrit that
approaches normal is attained. Lower maintenance doses (approximately 25 units/kg three times
a week) may subsequently be used. Iron supplementation is usually required, particularly during
the period when the hematocrit is increasing. (See "Treatment of iron deficiency in nondialysis
chronic kidney disease (CKD) patients" and "Treatment of iron deficiency in hemodialysis
patients".)
In one series of eight patients, erythropoietin increased the mean hematocrit from 34 to 45 percent
and the standing blood pressure from 81/46 to 100/63 [55]. Orthostatic dizziness improved in six
patients; three developed supine hypertension. The elevation in blood pressure may be mediated
by increases in red cell mass and central blood volume and by direct or indirect neurohumoral
effects on the vascular wall. (See "Hypertension following erythropoiesis-stimulating agents
(ESAs) in chronic kidney disease".)
Caffeine — The methylxanthine caffeine has a well-established pressor effect that is in part
due to blockade of vasodilating adenosine receptors. Caffeine improves orthostatic hypotension
and may attenuate postprandial hypotension in patients with autonomic failure. Caffeine may
exacerbate an existing tremor, however.
Typical doses are 100 to 250 mg three times a day with meals, either as tablets or caffeinated
beverages (one cup of coffee and tea contains approximately 85 and 50 mg of caffeine,
respectively) [57]. Because of the diuretic effect of caffeine, care should be taken to replenish
fluids and avoid dehydration.
Pyridostigmine — Acetylcholine is a neurotransmitter in the autonomic ganglia.

Acetylcholinesterase inhibition using pyridostigmine could thereby enhance ganglionic
neurotransmission, increase the release of norepinephrine by postganglionic sympathetic nerves,
and ameliorate orthostatic hypotension. Because postganglionic sympathetic nerves are activated
mainly during orthostatic stress, acetylcholinesterase inhibition may ameliorate orthostatic
hypotension without inducing supine hypertension, a common side effect of midodrine and other
sympathomimetics.
Pyridostigmine is usually initiated at a dose of 30 mg three times daily, up to a maximum dose of

90 mg three times daily.
There is limited evidence of efficacy for this treatment. In one double-blind, randomized, four-way
crossover study in 58 patients, a single dose of 60 mg of pyridostigmine alone or with midodrine
resulted in a small reduction of orthostatic hypotension (mean diastolic blood pressure fall of 27.2
versus 34 mmHg in placebo), without increasing supine blood pressure [58]. However, in a single-
blind randomized crossover trial of 31 patients with severe autonomic failure, a single dose of 60
mg of pyridostigmine did not increase the standing diastolic blood pressure [59]. In small open-
label studies, pyridostigmine appears inferior to midodrine and to fludrocortisone to improve
symptoms of neurogenic orthostatic hypotension [60,61]. Cholinergic side effects (cramping,
diarrhea, nausea) are often dose limiting.
Nonsteroidal antiinflammatory drugs — The NSAIDs are rarely effective as monotherapy,

but limited evidence suggests that they can supplement treatment with fludrocortisone or a
sympathomimetic agent. They probably act to limit the vasodilating effects of circulating
prostaglandins and arachidonic acid derivatives. They may also increase blood volume and
enhance vascular sensitivity to norepinephrine [62].
Third-line and experimental agents — Occasional patients require third-line or experimental

therapy to ameliorate the symptoms of orthostatic hypotension. Because data regarding these
agents are quite limited, patients should be so-advised and carefully monitored for adverse effects.
Such agents include atomoxetine, vasopressin analogues, yohimbine, and others as discussed
below. Beta blockers and clonidine are no longer recommended due to their hypotensive effects.
● Atomoxetine – Atomoxetine is a selective norepinephrine reuptake inhibitor that can be used

to treat attention deficit hyperactivity disorder in children, adolescents, and adults. In a trial in
65 patients with severe autonomic failure, administration of atomoxetine (18 mg) produced a
greater pressor response in upright systolic blood pressure and had a greater effect on
symptoms compared with the administration of midodrine (5 to 10 mg) or placebo [63].
Further study is required before it is certain whether this agent has a more routine role in the
treatment of orthostatic hypotension.
● Vasopressin analogues – Vasopressin analogues have a limited role in orthostatic

hypotension. Both V1 and V2 receptor agonists have been used. Their mechanism of action
may be enhanced by supersensitivity to vasopressin among patients with autonomic failure
because of reduced postural release of this hormone. V1 and V2 receptor agonists have
different modes of action.
• The synthetic vasopressin analogue desmopressin (DDAVP) acts on the V2 receptors in

the collecting tubules but has no V1 receptor vasoconstricting potential. DDAVP can be
taken via the nasal or oral route. In a three-day trial, DDAVP prevented nocturia and
overnight weight loss and reduced the morning postural fall in blood pressure in five
patients with autonomic failure [64]. Careful and continued monitoring of serum Na
concentration is required before and after initiating therapy. If hyponatremia develops,
treatment with DDAVP should be stopped.
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• The V1 receptor agonists, such as lysine-vasopressin nasal spray and intramuscular

triglycyl-lysine vasopressin, may increase blood pressure and peripheral vascular
resistance due to a direct vasopressor effect, thereby improving symptoms of orthostatic
hypotension [65]. No controlled clinical trial has been conducted, and therefore the use of
V1 receptor agonists cannot be recommended.
● Yohimbine – Yohimbine is a centrally active, selective alpha-2-adrenergic antagonist that

increases sympathetic nervous system efferent output by blocking central and/or presynaptic
alpha-2-adrenergic receptors (which are inhibitory). In subjects with residual sympathetic
nervous system outflow, yohimbine (8 mg three times daily) produces a modest pressor effect
[66]. Side effects include anxiety, tremor, palpitations, diarrhea, and supine hypertension.
Yohimbine has limited availability in the United States.
In a single-blind, randomized crossover treatment trial in 31 patients with severe autonomic

failure, a single dose of yohimbine (5.4 mg) was associated with an average 11 mmHg
improvement in standing diastolic blood pressure compared with placebo-treated patients
[59]. Patients also reported an improvement in presyncopal symptoms.
● Somatostatin – Somatostatin and somatostatin analogues such as octreotide attenuate the

pancreatic and gastrointestinal hormone response to food ingestion and other stimuli by
inhibiting the release of vasoactive gastrointestinal peptides. They also enhance cardiac
output and increase forearm and splanchnic vascular resistance. The net effect is attenuation
of the fall in the postprandial blood pressure in patients with autonomic failure [67].
Subcutaneous doses of octreotide range from 25 to 200 mcg. Side effects of nausea and
abdominal cramps limit the use of these agents.
● Dihydroergotamine – Dihydroergotamine, an ergot alkaloid that interacts with alpha-

adrenergic receptors, has a selective venoconstrictor effect. As a result, it may increase
venous return in patients with orthostatic hypotension without producing a significant increase
in peripheral vascular resistance. Although dihydroergotamine is an effective pressor
intravenously and intramuscularly, low oral bioavailability results in an inconsistent effect
when it is taken orally [68].
Ergotamine-caffeine (1 mg/100 mg) combination is available in tablet form for the treatment of
migraine and may be tried as occasional symptomatic treatment or up to twice-daily dosing in
patients with orthostatic hypotension [23]. No control trials support their efficacy.
● Dopamine antagonists – The dopamine antagonists, metoclopramide and domperidone

(which is not approved by the FDA), may be effective in chronic orthostatic hypotension [69].
Most likely, these agents inhibit the vasodilating and natriuretic effect of dopamine or increase
noradrenaline release by blocking prejunctional inhibitory dopamine receptors. These should

not be used in patients with parkinsonism. The risk of tardive dyskinesia and other
extrapyramidal side effects limits their long-term use.
● Monoamine oxidase inhibitors – Initial reports of combination therapy consisting of the

indirect acting agent tyramine (which releases norepinephrine from neuronal storage pools)
and a monoamine oxidase inhibitor (which prevents the breakdown of the released
norepinephrine) were optimistic. Unfortunately, this combination can cause severe supine
hypertension, an unpredictable response, and, in some cases, fails to abolish orthostatic
symptoms.
● Ambulatory norepinephrine infusion – In selected patients with refractory orthostatic

hypotension due to primary autonomic failure, ambulatory, patient-controlled infusion of
norepinephrine may be an effective therapy [70]. In one series of six patients, four had a
continued benefit from this therapy, without side effects, for up to 19 months [71].
SUPINE HYPERTENSION
A common problem in patients with orthostatic hypotension is the concurrent presence of supine
hypertension. Drugs effective in managing hypertension may exacerbate orthostatic hypotension,
while treatment of orthostatic hypotension may increase supine hypertension. In many such
patients, the best that can be achieved is to maximize nonpharmacologic measures and to use
drugs that might raise the supine blood pressure only to the degree that permits the patient to
ambulate.
Supine hypertension in patients with chronic autonomic failure can result in end-organ damage
[72,73]. It is uncertain what threshold of blood pressure requires treatment in this setting. Blood
pressure guidelines used in the general population will likely exacerbate orthostatic symptoms in
these patients.
No treatment approach to supine hypertension has been systematically evaluated. To offset

supine hypertension, patients should avoid lying down during the day, especially after taking
pressor agents, and, if tired, should rest in a seated position. Dosing of medications to avoid
administration within four hours of bedtime is also advised [5]. At night, patients should sleep in a
semisitting position with the head of the bed raised by at least 30 to 45 degrees.
No pharmacologic strategy can yet be recommended for the treatment of supine hypertension in
patients with neurogenic orthostatic hypotension. A transdermal nitroglycerin patch (0.025 to 0.1
mg/hour), which is removed in the morning prior to the assumption of an upright position, has
been proposed [74,75]. Other short-acting antihypertensive agents (eg, captopril, hydralazine)
may also be tried [23]. Significant hypotension may result in some patients; thus, the dose must be
individually titrated and tailored. To avoid syncope and dangerous falls, patients should be

cautioned to be extremely careful if they must arise at night, since orthostatic symptoms will be
exacerbated.
POSTPRANDIAL HYPOTENSION
In postprandial hypotension, blood pressure falls occur within one to two hours after a meal. As
with orthostatic hypotension, postprandial hypotension is common in older patients and in patients
with neurologic disorders [76]. (See "Mechanisms, causes, and evaluation of orthostatic
hypotension", section on 'Postprandial hypotension'.)
Optimal therapy of symptomatic postprandial hypotension has not been defined. The same
principles noted above for orthostatic hypotension (such as avoidance of volume depletion and
certain drugs) should also be applied to patients with postprandial symptoms. As an example,
among 20 patients with postprandial hypotension and heart failure but preserved left ventricular
systolic function, the successful withdrawal of furosemide in 13 significantly lessened the
maximum fall in both the systolic (-25 to -11 mmHg, p <0.001) and diastolic blood pressures (-18
to -9 mmHg, p = 0.01) [77].
Modification of meals (avoiding large and high-carbohydrate meals) as suggested above may also
be helpful in selected patients [27]. (See 'Modification of meals' above.)
Lying semirecumbent for 90 minutes after meals may be necessary for some patients. Patients
should try to walk in between meals.
In general, beneficial effects of medications have been demonstrated for blood pressure response,
but not for symptomatic improvement [78]:
● Acarbose, an alpha-glucosidase inhibitor and oral hypoglycemic agent, was found to

attenuate postprandial hypotension in a small trial of patients with autonomic failure [79].
● The somatostatin analogue octreotide minimizes postprandial hypotension, perhaps by

increasing splanchnic vascular resistance, thereby preventing pooling of blood in the gut
[27,80]. However, octreotide must be given subcutaneously (50 mcg, 30 minutes before each
meal), is expensive, and often leads to side effects such as diarrhea and pain at the injection
site.
● Caffeine has also been thought to be effective in this disorder [57] and has been shown to
reduce the magnitude of postprandial blood pressure falls in healthy volunteers [57,81-83].
However, a controlled trial in patients with postprandial syncope showed no attenuation of
blood pressure decline [84].
● 3,4-DL-threo-dihydroxyphenylserine administration three hours prior to a meal was associated

with a smaller reduction in blood pressure in a crossover study of 11 patients with autonomic

failure [85].
● Guar gum has been associated with an attenuated blood pressure response in healthy adults
as well as in patients with diabetes [86-88].
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Orthostatic hypotension (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Treatment should be geared to the patients' symptoms and their impact on daily function
rather than a target blood pressure. Persistent orthostatic blood pressure falls are common.
(See 'Treatment goals' above.)
● The initial treatment of orthostatic hypotension should focus on nonpharmacologic measures:

removal of offending medications (table 1), increasing salt and fluid intake, using elastic
stockings or an abdominal binder, physical maneuvers, and exercise (table 2). (See
'Nonpharmacologic measures' above.)
● For patients with persistent symptoms despite nonpharmacologic measures, we suggest step-
wise pharmacologic treatment starting with low-dose fludrocortisone (0.1 mg/day) for patients
with volume depletion and disabling symptoms despite nonpharmacologic measures (Grade
2C). A sympathomimetic pressor agent, such as midodrine or droxidopa, can be added or
substituted in patients who remain symptomatic on or cannot tolerate fludrocortisone. (See
'Fludrocortisone' above and 'Midodrine' above and 'Droxidopa' above.)
● When medications such as fludrocortisone, midodrine, or droxidopa are used, patients should
be instructed in avoiding the flat position, sleeping with the head of the bed raised 30 to 45
degrees, and measuring their own blood pressure. They should provide to the clinician, for
monitoring, a series of blood pressure recordings taken over several days, including when
supine, sitting, and standing upon awakening; before and one hour after lunch; and before
retiring to bed. (See 'Pharmacotherapy' above.)
● A number of other modalities may be beneficial (see 'Supplementary agents' above):
• Caffeine in the morning is probably helpful in many patients
• A trial with recombinant erythropoietin should be attempted in patients with neurogenic

orthostatic hypotension and anemia
● A small number of patients have persistent orthostatic symptoms despite these modalities.
Medication trials of agents with less clear evidence of benefit can be attempted in these
patients (table 2). (See 'Third-line and experimental agents' above.)
● Supine hypertension may be a treatment-limiting complication and may require specific

interventions. (See 'Supine hypertension' above.)
● Postprandial hypotension may respond to similar nonpharmacologic measures. Smaller

meals, with low carbohydrate and salt content, may also ameliorate symptoms. Rare patients
will require pharmacologic intervention. (See 'Postprandial hypotension' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Roy Freeman, MD, and Norman M
Kaplan, MD, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Palma JA, Kaufmann H. Epidemiology, Diagnosis, and Management of Neurogenic

Orthostatic Hypotension. Mov Disord Clin Pract 2017; 4:298.
2. Miller ER 3rd, Appel LJ. High prevalence but uncertain clinical significance of orthostatic
hypotension without symptoms. Circulation 2014; 130:1772.
3. Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, et al. Orthostatic hypotension in

Parkinson disease: how much you fall or how low you go? Mov Disord 2015; 30:639.
4. Mills PB, Fung CK, Travlos A, Krassioukov A. Nonpharmacologic management of orthostatic

hypotension: a systematic review. Arch Phys Med Rehabil 2015; 96:366.

5. Raj SR, Coffin ST. Medical therapy and physical maneuvers in the treatment of the
vasovagal syncope and orthostatic hypotension. Prog Cardiovasc Dis 2013; 55:425.
6. Wieling W, Raj SR, Thijs RD. Are small observational studies sufficient evidence for a
recommendation of head-up sleeping in all patients with debilitating orthostatic hypotension?
MacLean and Allen revisited after 70 years. Clin Auton Res 2009; 19:8.
7. Fan CW, Gasparro D, Crowley V, Cunningham CJ. Acute haemodynamic response to

sleeping head-up at 6 inches in older inpatients. Clin Auton Res 2009; 19:51.
8. Fan CW, Walsh C, Cunningham CJ. The effect of sleeping with the head of the bed elevated
six inches on elderly patients with orthostatic hypotension: an open randomised controlled
trial. Age Ageing 2011; 40:187.
9. Carroll JF, Wood CE, Pollock ML, et al. Hormonal responses in elders experiencing pre-
syncopal symptoms during head-up tilt before and after exercise training. J Gerontol A Biol
Sci Med Sci 1995; 50:M324.
10. Henry R, Rowe J, O'Mahony D. Haemodynamic analysis of efficacy of compression hosiery

in elderly fallers with orthostatic hypotension. Lancet 1999; 354:45.
11. Podoleanu C, Maggi R, Brignole M, et al. Lower limb and abdominal compression bandages
prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind
controlled study. J Am Coll Cardiol 2006; 48:1425.
12. Smit AA, Wieling W, Fujimura J, et al. Use of lower abdominal compression to combat
orthostatic hypotension in patients with autonomic dysfunction. Clin Auton Res 2004; 14:167.
13. Figueroa JJ, Singer W, Sandroni P, et al. Effects of patient-controlled abdominal

compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch
Phys Med Rehabil 2015; 96:505.
14. Fanciulli A, Goebel G, Metzler B, et al. Elastic abdominal binders attenuate orthostatic
hypotension in Parkinson's disease. Mov Disord 2015; 3:156.
15. Okamoto LE, Diedrich A, Baudenbacher FJ, et al. Efficacy of Servo-Controlled Splanchnic
Venous Compression in the Treatment of Orthostatic Hypotension: A Randomized
Comparison With Midodrine. Hypertension 2016; 68:418.
16. van Lieshout JJ, ten Harkel AD, Wieling W. Physical manoeuvres for combating orthostatic
dizziness in autonomic failure. Lancet 1992; 339:897.
17. Ten Harkel AD, van Lieshout JJ, Wieling W. Effects of leg muscle pumping and tensing on
orthostatic arterial pressure: a study in normal subjects and patients with autonomic failure.

Clin Sci (Lond) 1994; 87:553.
18. Krediet CT, Go-Schön IK, Kim YS, et al. Management of initial orthostatic hypotension: lower
body muscle tensing attenuates the transient arterial blood pressure decrease upon standing
from squatting. Clin Sci (Lond) 2007; 113:401.
19. Thijs RD, Wieling W, van den Aardweg JG, van Dijk JG. Respiratory countermaneuvers in
autonomic failure. Neurology 2007; 69:582.
20. Shannon JR, Diedrich A, Biaggioni I, et al. Water drinking as a treatment for orthostatic
syndromes. Am J Med 2002; 112:355.
21. Young TM, Mathias CJ. The effects of water ingestion on orthostatic hypotension in two
groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure. J
Neurol Neurosurg Psychiatry 2004; 75:1737.
22. Humm AM, Mason LM, Mathias CJ. Effects of water drinking on cardiovascular responses to
supine exercise and on orthostatic hypotension after exercise in pure autonomic failure. J
Neurol Neurosurg Psychiatry 2008; 79:1160.
23. Nwazue VC, Raj SR. Confounders of vasovagal syncope: orthostatic hypotension. Cardiol
Clin 2013; 31:89.
24. Fedorowski A, Melander O. Syndromes of orthostatic intolerance: a hidden danger. J Intern

Med 2013; 273:322.
25. Shibao C, Lipsitz LA, Biaggioni I. ASH position paper: evaluation and treatment of orthostatic
hypotension. J Clin Hypertens (Greenwich) 2013; 15:147.
26. Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am
Fam Physician 2011; 84:527.
27. Jansen RW, Lipsitz LA. Postprandial hypotension: epidemiology, pathophysiology, and
clinical management. Ann Intern Med 1995; 122:286.
28. Lipsitz LA, Nyquist RP Jr, Wei JY, Rowe JW. Postprandial reduction in blood pressure in the
elderly. N Engl J Med 1983; 309:81.
29. Biaggioni I, Arthur Hewitt L, Rowse GJ, Kaufmann H. Integrated analysis of droxidopa trials
for neurogenic orthostatic hypotension. BMC Neurol 2017; 17:90.
30. Logan IC, Witham MD. Efficacy of treatments for orthostatic hypotension: a systematic
review. Age Ageing 2012; 41:587.

31. Schoffer KL, Henderson RD, O'Maley K, O'Sullivan JD. Nonpharmacological treatment,
fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. Mov
Disord 2007; 22:1543.
32. Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet
Neurol 2008; 7:451.
33. Norcliffe-Kaufmann L, Kaufmann H. Is ambulatory blood pressure monitoring useful in

patients with chronic autonomic failure? Clin Auton Res 2014; 24:189.
34. Campbell IW, Ewing DJ, Clarke BF. 9-Alpha-fluorohydrocortisone in the treatment of postural
hypotension in diabetic autonomic neuropathy. Diabetes 1975; 24:381.
35. Davies IB, Bannister RG, Sever PS, Wilcox CS. Fludrocortisone in the treatment of postural
hypotension: altered sensitivity to pressor agents [proceedings]. Br J Clin Pharmacol 1978;
6:444P.
36. Chobanian AV, Volicer L, Tifft CP, et al. Mineralocorticoid-induced hypertension in patients
with orthostatic hypotension. N Engl J Med 1979; 301:68.
37. Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of
hypotensive disorders in the elderly. Heart 1996; 76:507.
38. Davies B, Bannister R, Sever P. Pressor amines and monoamine-oxidase inhibitors for
treatment of postural hypotension in autonomic failure. Limitations and hazards. Lancet
1978; 1:172.
39. Ghrist DG, Brown GE. Postural hypertension with syncope: Its successful treatment with
ephedrine. Am J Med Sci 1928; 175:336.
40. Biaggioni I, Onrot J, Stewart CK, Robertson D. The potent pressor effect of
phenylpropanolamine in patients with autonomic impairment. JAMA 1987; 258:236.
41. Kaufmann H, Brannan T, Krakoff L, et al. Treatment of orthostatic hypotension due to

autonomic failure with a peripheral alpha-adrenergic agonist (midodrine). Neurology 1988;
38:951.
42. Smith W, Wan H, Much D, et al. Clinical benefit of midodrine hydrochloride in symptomatic
orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table
study. Clin Auton Res 2016; 26:269.
43. Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine vs placebo in neurogenic
orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study
Group. JAMA 1997; 277:1046.

44. Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of
neurocardiogenic syncope. Heart 1998; 79:45.
45. Izcovich A, González Malla C, Manzotti M, et al. Midodrine for orthostatic hypotension and
recurrent reflex syncope: A systematic review. Neurology 2014; 83:1170.
46. Parsaik AK, Singh B, Altayar O, et al. Midodrine for orthostatic hypotension: a systematic
review and meta-analysis of clinical trials. J Gen Intern Med 2013; 28:1496.
47. Freeman R, Landsberg L. The treatment of orthostatic hypotension with

dihydroxyphenylserine. Clin Neuropharmacol 1991; 14:296.
48. Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic
hypotension associated with Parkinson's disease (NOH306A). J Parkinsons Dis 2014; 4:57.
49. Kaufmann H, Saadia D, Voustianiouk A, et al. Norepinephrine precursor therapy in

neurogenic orthostatic hypotension. Circulation 2003; 108:724.
50. Mathias CJ, Senard JM, Braune S, et al. L-threo-dihydroxyphenylserine (L-threo-DOPS;

droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-
center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton
Res 2001; 11:235.
51. Elgebaly A, Abdelazeim B, Mattar O, et al. Meta-analysis of the safety and efficacy of
droxidopa for neurogenic orthostatic hypotension. Clin Auton Res 2016; 26:171.
52. Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Droxidopa in neurogenic orthostatic

hypotension. Expert Rev Cardiovasc Ther 2015; 13:875.
53. Chen JJ, Han Y, Tang J, et al. Standing and Supine Blood Pressure Outcomes Associated
With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A
Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials. Ann
Pharmacother 2018; 52:1182.
54. Palma JA, Norcliffe-Kaufmann L, Martinez J, Kaufmann H. Supine plasma NE predicts the
pressor response to droxidopa in neurogenic orthostatic hypotension. Neurology 2018;
91:e1539.
55. Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. N Engl
J Med 1993; 329:611.
56. Perera R, Isola L, Kaufmann H. Effect of recombinant erythropoietin on anemia and

orthostatic hypotension in primary autonomic failure. Clin Auton Res 1995; 5:211.

57. Onrot J, Goldberg MR, Biaggioni I, et al. Hemodynamic and humoral effects of caffeine in
autonomic failure. Therapeutic implications for postprandial hypotension. N Engl J Med
1985; 313:549.
58. Singer W, Sandroni P, Opfer-Gehrking TL, et al. Pyridostigmine treatment trial in neurogenic
orthostatic hypotension. Arch Neurol 2006; 63:513.
59. Shibao C, Okamoto LE, Gamboa A, et al. Comparative efficacy of yohimbine against
pyridostigmine for the treatment of orthostatic hypotension in autonomic failure.
Hypertension 2010; 56:847.
60. Byun JI, Moon J, Kim DY, et al. Efficacy of single or combined midodrine and pyridostigmine
in orthostatic hypotension. Neurology 2017; 89:1078.
61. Schreglmann SR, Büchele F, Sommerauer M, et al. Pyridostigmine bromide versus

fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a
randomized controlled trial. Eur J Neurol 2017; 24:545.
62. Kochar MS, Itskovitz HD. Treatment of idiopathic orthostatic hypotension (Shy-Drager
syndrome) with indomethacin. Lancet 1978; 1:1011.
63. Ramirez CE, Okamoto LE, Arnold AC, et al. Efficacy of atomoxetine versus midodrine for the
treatment of orthostatic hypotension in autonomic failure. Hypertension 2014; 64:1235.
64. Mathias CJ, Fosbraey P, da Costa DF, et al. The effect of desmopressin on nocturnal
polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic
failure. Br Med J (Clin Res Ed) 1986; 293:353.
65. Kochar MS. Hemodynamic effects of lysine-vasopressin in orthostatic hypotension. Am J

Kidney Dis 1985; 6:49.
66. Onrot J, Goldberg MR, Biaggioni I, et al. Oral yohimbine in human autonomic failure.
Neurology 1987; 37:215.
67. Hoeldtke RD, Israel BC. Treatment of orthostatic hypotension with octreotide. J Clin
Endocrinol Metab 1989; 68:1051.
68. Jennings G, Esler M, Holmes R. Treatment of orthostatic hypotension with

dihydroergotamine. Br Med J 1979; 2:307.
69. Lopes de Faria SR, Zanella MT, Andriolo A, et al. Peripheral dopaminergic blockade for the
treatment of diabetic orthostatic hypotension. Clin Pharmacol Ther 1988; 44:670.
70. Goldstein DS, Sewell L, Holmes C, et al. Temporary elimination of orthostatic hypotension by
norepinephrine infusion. Clin Auton Res 2012; 22:303.
71. Oldenburg O, Mitchell A, Nürnberger J, et al. Ambulatory norepinephrine treatment of severe

autonomic orthostatic hypotension. J Am Coll Cardiol 2001; 37:219.
72. Sandroni P, Benarroch EE, Wijdicks EF. Caudate hemorrhage as a possible complication of
midodrine-induced supine hypertension. Mayo Clin Proc 2001; 76:1275.
73. Kaufmann H. Primary autonomic failure: three clinical presentations of one disease? Ann
Intern Med 2000; 133:382.
74. Shannon J, Jordan J, Costa F, et al. The hypertension of autonomic failure and its treatment.
Hypertension 1997; 30:1062.
75. Jordan J, Shannon JR, Pohar B, et al. Contrasting effects of vasodilators on blood pressure
and sodium balance in the hypertension of autonomic failure. J Am Soc Nephrol 1999;
10:35.
76. Pavelić A, Krbot Skorić M, Crnošija L, Habek M. Postprandial hypotension in neurological

disorders: systematic review and meta-analysis. Clin Auton Res 2017; 27:263.
77. van Kraaij DJ, Jansen RW, Bouwels LH, Hoefnagels WH. Furosemide withdrawal improves
postprandial hypotension in elderly patients with heart failure and preserved left ventricular
systolic function. Arch Intern Med 1999; 159:1599.
78. Ong AC, Myint PK, Potter JF. Pharmacological treatment of postprandial reductions in blood
pressure: a systematic review. J Am Geriatr Soc 2014; 62:649.
79. Shibao C, Gamboa A, Diedrich A, et al. Acarbose, an alpha-glucosidase inhibitor, attenuates

postprandial hypotension in autonomic failure. Hypertension 2007; 50:54.
80. Alam M, Smith G, Bleasdale-Barr K, et al. Effects of the peptide release inhibitor, octreotide,
on daytime hypotension and on nocturnal hypertension in primary autonomic failure. J
Hypertens 1995; 13:1664.
81. Heseltine D, Dakkak M, Woodhouse K, et al. The effect of caffeine on postprandial

hypotension in the elderly. J Am Geriatr Soc 1991; 39:160.
82. Lenders JW, Morre HL, Smits P, Thien T. The effects of caffeine on the postprandial fall of
blood pressure in the elderly. Age Ageing 1988; 17:236.
83. Rakic V, Beilin LJ, Burke V. Effect of coffee and tea drinking on postprandial hypotension in
older men and women. Clin Exp Pharmacol Physiol 1996; 23:559.
84. Lipsitz LA, Jansen RW, Connelly CM, et al. Haemodynamic and neurohumoral effects of
caffeine in elderly patients with symptomatic postprandial hypotension: a double-blind,

randomized, placebo-controlled study. Clin Sci (Lond) 1994; 87:259.
85. Freeman R, Young J, Landsberg L, Lipsitz L. The treatment of postprandial hypotension in

autonomic failure with 3,4-DL-threo-dihydroxyphenylserine. Neurology 1996; 47:1414.
86. Jones KL, MacIntosh C, Su YC, et al. Guar gum reduces postprandial hypotension in older
people. J Am Geriatr Soc 2001; 49:162.
87. Russo A, Stevens JE, Wilson T, et al. Guar attenuates fall in postprandial blood pressure
and slows gastric emptying of oral glucose in type 2 diabetes. Dig Dis Sci 2003; 48:1221.
88. Jones KL, Tonkin A, Horowitz M, et al. Rate of gastric emptying is a determinant of
postprandial hypotension in non-insulin-dependent diabetes mellitus. Clin Sci (Lond) 1998;
94:65.
Topic 5105 Version 15.0

GRAPHICS
Examples of drugs that can cause or exacerbate orthostatic hypotension
Alcohol
Alpha blockers: Terazosin (eg)
Antidepressant drugs: Selective serotonin receptor reuptake inhibitors, trazodone, monoamine oxidase inhibitors,
tricyclic antidepressants
Antihypertensive drugs: Sympathetic blockers (eg)
Antiparkinsonism drugs: Levodopa, pramipexole, ropinirole (egs)
Antipsychotic drugs: Olanzapine, risperidone (egs)
Beta-blocker drugs: Propranolol (eg)
Diuretic drugs: Hydrochlorothiazide, furosemide (egs)
Muscle relaxant drugs: Tizanidine (eg)
Narcotic analgesic drugs: Morphine (eg)
Phosphodiesterase inhibitors: Sildenafil, tadalafil (egs)
Sedatives/hypnotic drugs: Temazepam (eg)
Vasodilator drugs: Hydralazine, nitroglycerin, calcium channel blockers (egs)
Reproduced with permission from: Perlmuter LC, Sarda G, Casavant V, Mosnaim AD. A review of the etiology, associated
comorbidities, and treatment of orthostatic hypotension. Am J Ther 2013; 20:279. DOI: 10.1097/MJT.0b013e31828bfb7f.
Copyright © 2013 Wolters Kluwer Health, Lippincott Williams & Wilkins. Unauthorized reproduction of this material is
prohibited.
Graphic 89955 Version 9.0

Management of chronic orthostatic hypotension
Correct precipitating factors (eg, hypovolemia) and withdraw offending drugs

(diuretics, vasodilators, tranquilizers, and sedatives)
Physical measures
Raise the head of the bed by 10 to 20°
Arise slowly, in stages, from supine to seated to standing
Dorsiflexion of the feet, handgrip isometric, leg crossing/squatting before standing
Liberalize salt and fluid intake
Small meals and coffee only in the early morning
Fitted compression stockings and pressure suits (often not acceptable)
Drugs
Fludrocortisone
Sympathomimetic drugs – midodrine, droxidopa

Supplementary agents
Erythropoietin (if anemic)
Caffeine
Pyridostigmine
Nonsteroidal anti-inflammatory drugs
Third-line and experimental drugs
Vasopressin receptor agonists – desmopressin, lysine vasopressin

Yohimbine
Somatostatin analogues – octreotide, especially for postprandial hypotension

Dihydroergotamine
Fluoxetine
Dihydroxyphenylserine
Dopamine antagonists – metoclopramide, domperidone

Monoamine oxidase inhibitor with tyramine – can produce severe hypertension
Graphic 59499 Version 5.0

Contributor Disclosures
Horacio Kaufmann, MD Grant/Research/Clinical Trial Support: Familial Dysautonomia Foundation [Familial
dysautonomia]; National Institutes of Health [Parkinson disease, multiple system atrophy]; US Food and Drug
Administration [Familial dysautonomia]; Michael J Fox Foundation [Parkinson disease]; Multiple System
Atrophy Coalition [Multiple system atrophy]. Consultant/Advisory Boards: Lundbeck [Neurogenic orthostatic
hypotension]; Theravance Biopharma [Neurogenic orthostatic hypotension]. Michael J Aminoff, MD,
DSc Equity Ownership/Stock Options: Trust [The portfolio may include medical or drug companies]. Equity
Ownership/Stock Options (Spouse): Trust [The portfolio may include medical or drug companies]. Peter
Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: Cardionet/BioTelemetry [Cardiac
monitoring]. Consultant/Advisory Boards: Acesion Pharma; InCarda Therapeutics; Boehringer-Ingelheim;
Bristol-Meyers Squibb; Daiichi Sankyo; Johnson & Johnson; Medtronic; Gilead; Forest; Pfizer; Sanofi;
Servier; Portola; Milestone; INSTA [Arrhythmias]. Janet L Wilterdink, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
Conflict of interest policy

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Official reprint from UpToDate®

https://www.uptodate.com/contents/treatment-of-orthostatic-and-postprandial-hypotension/print?search=ortostatic hypotension&source=search_r… 1/25

Nonpharmacologic measures are an important first-line therapy for neurogenic orthostatic

Discontinue exacerbating medications — Recognition and discontinuation of drugs that cause

● Maintaining adequate hydration and avoiding overheating.

https://www.uptodate.com/contents/treatment-of-orthostatic-and-postprandial-hypotension/print?search=ortostatic hypotension&source=search_r… 2/25

● Modifying meals by reducing high glycemic-index carbohydrate content can be helpful,

Compression stockings and abdominal binders

open-label follow-up, improved symptoms of orthostatic hypotension as assessed by

● Respiratory maneuvers are under investigation as a means of treating orthostatic hypotension

urinary sodium level of 150 to 200 mEq [23-26].

● Avoiding large meals

Nonpharmacologic measures are often insufficient to prevent symptoms of orthostatic

Step-wise approach and monitoring — Nonpharmacologic measures should be maximized prior

https://www.uptodate.com/contents/treatment-of-orthostatic-and-postprandial-hypotension/print?search=ortostatic hypotension&source=search_r… 5/25

Fludrocortisone — Fludrocortisone acetate (9-alpha-fluorohydrocortisone), a synthetic

Potassium supplementation is usually required, particularly when higher doses of fludrocortisone

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Droxidopa — L-dihydroxyphenylserine (DOPS, droxidopa) is a synthetic amino acid,

Since the conversion of droxidopa to norepinephrine bypasses the dopamine beta-hydroxylation

Supplementary agents — Erythropoietin, caffeine, pyridostigmine, and nonsteroidal

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Erythropoietin — Recombinant human erythropoietin increases standing blood pressure and

Recombinant human erythropoietin, epoetin alpha, is administered subcutaneously or

Pyridostigmine — Acetylcholine is a neurotransmitter in the autonomic ganglia.

Pyridostigmine is usually initiated at a dose of 30 mg three times daily, up to a maximum dose of

Nonsteroidal antiinflammatory drugs — The NSAIDs are rarely effective as monotherapy,

Third-line and experimental agents — Occasional patients require third-line or experimental

● Atomoxetine – Atomoxetine is a selective norepinephrine reuptake inhibitor that can be used

● Vasopressin analogues – Vasopressin analogues have a limited role in orthostatic

• The synthetic vasopressin analogue desmopressin (DDAVP) acts on the V2 receptors in

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• The V1 receptor agonists, such as lysine-vasopressin nasal spray and intramuscular

● Yohimbine – Yohimbine is a centrally active, selective alpha-2-adrenergic antagonist that

In a single-blind, randomized crossover treatment trial in 31 patients with severe autonomic

● Somatostatin – Somatostatin and somatostatin analogues such as octreotide attenuate the

● Dihydroergotamine – Dihydroergotamine, an ergot alkaloid that interacts with alpha-

● Dopamine antagonists – The dopamine antagonists, metoclopramide and domperidone

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● Monoamine oxidase inhibitors – Initial reports of combination therapy consisting of the

● Ambulatory norepinephrine infusion – In selected patients with refractory orthostatic

No treatment approach to supine hypertension has been systematically evaluated. To offset

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● Acarbose, an alpha-glucosidase inhibitor and oral hypoglycemic agent, was found to

● The somatostatin analogue octreotide minimizes postprandial hypotension, perhaps by

● 3,4-DL-threo-dihydroxyphenylserine administration three hours prior to a meal was associated

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INFORMATION FOR PATIENTS

● Basics topics (see "Patient education: Orthostatic hypotension (The Basics)")

SUMMARY AND RECOMMENDATIONS

● The initial treatment of orthostatic hypotension should focus on nonpharmacologic measures:

● A number of other modalities may be beneficial (see 'Supplementary agents' above):

• Caffeine in the morning is probably helpful in many patients

• A trial with recombinant erythropoietin should be attempted in patients with neurogenic

● Supine hypertension may be a treatment-limiting complication and may require specific

● Postprandial hypotension may respond to similar nonpharmacologic measures. Smaller

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1. Palma JA, Kaufmann H. Epidemiology, Diagnosis, and Management of Neurogenic

3. Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, et al. Orthostatic hypotension in

4. Mills PB, Fung CK, Travlos A, Krassioukov A. Nonpharmacologic management of orthostatic

https://www.uptodate.com/contents/treatment-of-orthostatic-and-postprandial-hypotension/print?search=ortostatic hypotension&source=search… 15/25

7. Fan CW, Gasparro D, Crowley V, Cunningham CJ. Acute haemodynamic response to