Official Journal of the Society of Hospital Pharmacists of Australia

G E R I AT R I C T H E R A P E U T I C S R E V I E W
EDITED BY ROHAN A. ELLIOTT, BPHARM, BPHARMSC (HONS), MCLINPHARM, PHD, BCGP, FSHP

Review of management strategies for orthostatic hypotension in

older people
Gauri P. Godbole, BPharm, MClinPharm, BCGP, MSHP1, Bhavna Aggarwal, MBBS, FRACP2
1 Gosford Hospital Pharmacy Department, Central Coast Local Health District, Gosford, Australia
2 Central Coast Local Health District, Gosford, Australia

Abstract
Orthostatic hypotension (OH) is common in older people and is associated with a range of adverse outcomes. Although age-
related changes like decreased baroreflex sensitivity make older people prone to OH, medications are often a contributor. Diag-
nosis of OH can be challenging in older people, because the condition may present with atypical or non-specific symptoms,
such as visual disturbances, shortness of breath, mental fluctuation. Non-pharmacological management is often a starting point
for OH treatment. Fludrocortisone and midodrine remain the most studied drugs for pharmacological management, but newer
agents are being tested. In this review we present the current evidence for existing and emerging treatments for OH and
address the management of supine hypertension associated with the treatment of OH in patients with autonomic failure. In the
management of OH, it is imperative that treatment is tailored to the individual, rather than focusing on attaining an arbitrary
blood pressure target.

Keywords: orthostatic hypotension, management, older people, supine hypertension.

INTRODUCTION hypertension (supine SBP ≥160 mmHg), a more appro-

Orthostatic hypotension (OH) is common in older
adults, and its incidence increases with age.1 OH is an
important cause of syncope and falls, and may con-
tribute to morbidity, all-cause mortality and reduced
quality of life.2 Patients with OH may develop coronary
events, stroke and have a poor prognosis, especially if
they have comorbidities such as diabetes and Parkin-
son’s disease.3–5
DEFINITION
The latest consensus statement published in 2011 defines
OH as a drop in blood pressure (BP) of at least
20 mmHg for systolic BP (SBP) or 10 mmHg for dias-
tolic BP (DBP) within 3 min of standing or during a
head-up tilt test to at least 60°.6 In patients with
Address for correspondence: Gauri P. Godbole, Pharmacy Depart-
ment, Gosford Hospital, Holden Street, Gosford, NSW 2250,
Australia.
E-mail: godbolegp@gmail.com
priate criterion for the diagnosis of OH would be a drop
in SBP of at least 30 mmHg.5,6
The 2011 consensus statement also identifies two vari-
ants of OH: initial OH and delayed OH.6 In initial OH,
there is an exaggerated transient fall in BP (>40 mmHg
SBP and/or 20 mmHg DBP) accompanied by symptoms
of hypoperfusion within 15 s of standing. Initial OH
may occur during active standing and, to a lesser extent,
with passive tilting. In delayed OH, symptoms occur
beyond 3 min of standing. The clinical significance of
this latter form of OH is not well defined, but may
reveal an early or mild form of sympathetic adrenergic
failure.7,8
In clinical practice, when using intermittent BP mea-
surements, the first measurement should be taken 30 s
after standing, and the second measurement at 60 s.3,5
This is because the nadir of BP drop usually occurs
within 30–60 s.3 Subsequent measurements should be
taken at 1-min intervals, usually for a total of 3 min. In
patients with suspected neurogenic OH, extending the
test to up to 10 min may be helpful to check for delayed
OH.2

© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 483–491
doi: 10.1002/jppr.1484

484
PREVALENCE AND IMPLICATIONS
The prevalence of OH in community-dwelling older
people has been reported to vary between 9% and
34%.9,10 In the Cardiovascular Health Study,11of 5201
American men and women aged over 65 years, 16.2%
had asymptomatic OH. Another 2.0% had symp-
tomatic OH presenting as dizziness, light headedness
or faintness.11,12 In aged care facilities and acute hos-
pital settings, OH prevalence as high as 50% has
been reported.3 It has also been reported that OH
affects 25% of patients with type 2 diabetes mellitus
(T2DM) and 70% of patients with Parkinson’s
disease.5
Several studies have shown that OH is an indepen-
dent risk factor for morbidity and mortality,13,14 and a
decline in SBP >20 mmHg is a risk factor for falls, espe-
cially in older patients with hypertension. Older people
with OH are most likely to be physically frail with
decreased functional capacity. OH is often overlooked as
a cause of frailty in older patients in whom orthostatic
vital signs are rarely obtained.15
OH in the older adult may increase the risk of cere-
bral hypoxic changes leading to cognitive decline and
dementia.16 It is therefore recommended that BP moni-
toring, including orthostatic testing, be routinely per-
formed in this population.16 OH also increases the risk
of cardiovascular disease and all-cause mortality in
older people, and is associated with syncope, falls and
fractures, which may lead to functional impairment and
hospitalisation.17
PATHOPHYSIOLOGY OF OH
When a healthy person stands, approximately 700 mL
blood pools below the diaphragm and results in
decreased venous return to the heart, reduced ventricu-
lar filling and a transient decrease in cardiac output.18
The consequent baroreflex-mediated sympathetic activa-
tion, along with parasympathetic withdrawal, results in
increased heart rate, stroke volume and peripheral vaso-
constriction, maintaining BP. In a healthy subject, this
orthostatic stabilisation is normally achieved within
1 min of standing. A failure of any of these systems can
lead to OH.11,19,20
Aging-related changes, like decreased baroreflex sensi-
tivity, which manifests as decreased heart rate and a1-adre-
noceptor vasoconstrictor response to sympathetic stimuli
upon standing, can make older people prone to OH.18 A
reduction in renal salt and water conservation and cardiac
filling also increase the risk of OH in older people.18
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G. P. Godbole and B. Aggarwal
SYMPTOMS OF OH
Clinical manifestations are due to hypoperfusion or
overcompensation. Symptoms related to cerebral
hypoperfusion include light-headedness, dizziness,
weakness, difficulty thinking and feeling faint. Com-
pensatory autonomic overreaction can cause palpita-
tions, tremulousness, nausea, coldness of extremities
and chest pain.21
There is not always a correlation between the fall in
BP and the symptoms of OH. Up to 80% of patients
with OH may be asymptomatic. Some patients may
present with symptoms not usually attributed to OH,
like shortness of breath, chest pain, seizures or dizzi-
ness after a meal (post-meal syncope).2 Patients with
dementia may present with mental fluctuations, confu-
sion, drowsiness and falls.22 Other atypical symptoms
of OH can include dim, blurred or tunnel vision, or a
dull pain in the back of the neck and shoulder (coat
hanger distribution) induced by reduced muscular
flow.14,15 The circumstances in which symptoms occur
must be carefully analysed in order to identify OH as
a possible cause.14
CAUSES OF OH
Causes of OH can be broadly classified into neurogenic
and non-neurogenic (Table 1).
A peripheral or central neurological lesion can cause
autonomic dysfunction and a failure to correct for tran-
sient falls in BP upon standing.13 Multisystem atrophy
(MSA) is a central disorder that causes autonomic dys-
function. Peripheral causes include neurodegenerative
disorders like Parkinson’s disease and pure autonomic
failure (PAF).13,23 OH can also be observed as secondary
autonomic insufficiency in conditions such as diabetes
and amyloidosis.13,23
Medications represent a major non-neurogenic cause
of OH. The main culprits are antihypertensive medica-
tions, in particular beta-blockers24 and a-adrenoceptor
antagonists (including those prescribed for urinary dis-
orders), vasodilators, diuretics, antiparkinsonian drugs
and some antipsychotics (most antipsychotics have a
propensity to cause OH, but OH is more prevalent with
clozapine and olanzapine).25–27
In a study conducted at a US Veterans Affairs geriatric
clinic, the prevalence of OH in patients receiving zero,
one, two and three or more potentially causative medica-
tions was 35%, 58%, 60% and 65%, respectively.28 The
ACTION (A large-scale open-label clinical experience
trial) study investigators found that antihypertensive
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Orthostatic hypotension in older people 485

Table 1 Causes of orthostatic hypotension3,13,14,23,46

Neurogenic causes
Parkinson’s disease
Multisystem atrophy
Pure autonomic failure
Dementia with Lewy bodies
Diabetic autonomic nephropathy
Amyloidosis (familial and primary)
Dopamine b-hydroxylase deficiency
Autoimmune autonomic gangliopathy
Hereditary sensory and autonomic neuropathies
Other peripheral neuropathies (alcohol, paraneoplastic, HIV, Guillain-Barr
e syndrome)
Spinal cord or brain stem lesions
Sj€
ogren’s syndrome
Pernicious anaemia
Chronic renal failure
Non-neurogenic causes
Medications (particularly a-adrenoceptor antagonists, antipsychotics, antihypertensives, diuretics, vasodilators such as nitrates,
sympatholytics such as beta-blockers, narcotics, sedatives, tricyclic antidepressants, levodopa and sildenafil)
Sepsis
Dehydration or volume depletion (e.g. secondary to burns, diarrhoea, vomiting, haemorrhage, heat, salt-free diet)
Cardiac causes (e.g. brady- or tachyarrhythmia, myocardial infarction, hypertension, diastolic dysfunction, baroreceptor insensitivity)
Large carbohydrate-rich meals and alcohol
Adrenal insufficiency
Deconditioning (following acute illness and a period of recumbence)
Other metabolic causes (e.g. vitamin B12 deficiency, porphyria)

drugs that act on the renin–angiotensin system were well
tolerated in older people.29
Significant postural falls in BP can be associated with
meals (postprandial OH), especially after consumption
of a large meal high in carbohydrates, due to gastric dis-
tension, release of vasodilatory peptides and splanchnic
blood pooling.6,14 Genetic predisposition towards OH
has not been comprehensively explored.23 Long periods
of immobilisation, such as during a hospital stay, can
also make older patients more susceptible to OH.15,30
Reduced cardiac filling (due to an increase in heart
stiffness) and a reduction in renal salt and water conser-
vation during periods of fluid restriction or volume loss
(due to reduced renin, angiotensin and aldosterone and
increased natriuretic peptides) also increase the risk of
hypotension in older people.18
OH is more common and more severe in the morn-
ing, most likely due to nocturnal supine hypertension,
which causes a pressure diuresis. This may cause signifi-
cant intravascular volume loss overnight, thus increas-
ing the risk of morning hypotension.6,30
MANAGEMENT GOALS
The treatment of OH should be directed towards ame-
liorating the symptoms, correcting any underlying
cause, improving functional status and reducing the risk
of complications rather than aiming for an arbitrary BP
goal.18 Using relative decreases in BP to guide treatment
may be more appropriate in clinical practice.31 With the
exception of a ≥ 25% decrease in SBP or DBP, the clini-
cal relevance of asymptomatic OH BP measurements
(identified on OH screening) seems very limited with
regard to orthostatic complaints or fall incidents. Each
patient must have an individualised treatment plan that
is reassessed and modified on a regular basis to ascer-
tain benefit and side effects of the current regimen.2
MANAGEMENT OF OH
Diagnosis of OH in older people is often challenging
because of comorbid conditions and non-specific OH
symptomatology. Initial management should always
include screening for acute precipitants, such as medica-
tions and hypovolaemia. A thorough medication history
is of paramount importance in identifying drug causes
of OH.
Management of OH can be broadly classified into
non-pharmacological and pharmacological interventions.
Non-pharmacological Measures
Non-pharmacological measures, including patient educa-
tion, should be the first line of treatment.3,30 A

© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 483–491

486
Table 2 Non-pharmacological measures for the treatment of orthostatic hypotension36
Recommendation
Recommended for all patients
Education and reassurance, including explanation of diagnosis, risk of
recurrence and the avoidance of triggers
Adequate hydration and salt intake
Should be considered
Modification or discontinuation of hypotensive drug
regimens
Isometric physical counter-pressure manoeuvres
Abdominal binders and/or compression stockings
Head-up tilt sleeping (>10°)
systematic review identified physical and dietary mea-
sures as two major non-pharmacological treatment cate-
gories.32 Physical measures include compression
stockings (abdominal or lower limbs), exercise, physical
counter-manoeuvres and sleeping with the head ele-
vated. Dietary measures to limit postprandial OH
include eating small, frequent meals low in rapidly
absorbed carbohydrate.14,32 Adequate hydration, by
drinking one to two large glasses of water before each
meal, helps limit postprandial hypotension associated
with neurogenic OH.14
Elevating the head and neck during the night (>10°)
can activate the carotid and aortic baroreceptors and
renin–angiotensin–aldosterone system to control supine
hypertension and reduce early morning hypotension.14
When rising from a bed, patients should be advised to
move to a head-up position slowly and to sit on edge
of the bed for a few minutes prior to standing. Activat-
ing the calf muscles while supine, prior to rising, also
helps.
Patients who do not respond to simple measures may
benefit from physical counter manoeuvres (e.g. crossing
the legs while standing, squatting, marching in place),
which cause compression of splanchnic vessels, increase
abdominal pressure, venous return and reduce blood
pooling.4 However, this can be challenging for some
because it requires a certain level of mobility and bal-
ance.2,4,32 In older people with OH due to deconditioning,
an exercise regimen including swimming or recumbent
biking may also help attenuate symptoms.18
Some observational studies have suggested that
abdominal support garments are better at preventing OH
than leg garments.33 Limb and abdominal compression
may improve orthostatic tolerance in up to 40% of
patients. The recommended compression pressure is
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G. P. Godbole and B. Aggarwal
Evidence
Expert consensus opinion, small studies, retrospective studies
and registries
Expert consensus opinion, small studies, retrospective studies
and registries
Single randomised clinical trial, large non-randomised studies
Expert consensus opinion, small studies, retrospective studies
and registries
Single randomised clinical trial, large non-randomised studies
Expert consensus opinions, small studies, retrospective studies,
and registries
30–50 mmHg for leg compression and 20–30 mmHg for
abdominal compression.30 Although they are inconve-
nient to apply and can be uncomfortable during warm
weather, the positive effects of support garments are often
recognised by the patient and can be used as needed
when a prolonged orthostatic challenge is expected.30
Volume expansion by increased salt and fluid remains
a cornerstone in patients with OH and no contraindica-
tions. Caution should be exercised in patients with heart
or kidney failure and supine hypertension.23,34 The pres-
sor response of water takes 5–10 min to start, peaks
between 20 and 40 min after ingestion and starts to
wane by 60 min.13 A bolus of two glasses of 240 mL
water in rapid succession improves SBP by 20 mmHg.3
If this fails to attenuate the symptoms, patients should
be encouraged to increase salt intake up to 6–10 g/day
and water intake to 1.5–2.0 L/day.35 Sodium excretion
>170 mmol/day confirms adequate salt intake.3
Antihypertensive medication withdrawal remains con-
troversial, and recent clinical trials have done little to clear
the uncertainty.5 Treatment of OH requires balancing the
risks of hypertension against the potential hypotensive
effects of medications.3 In patients with established OH
and at risk of falls, aggressive BP-lowering treatment
should be avoided. The revision of hypertension treat-
ment targets to SBP of 140–150 mmHg should be consid-
ered.14 Withdrawal of provoking agents (Table 1) may be
helpful if they are suspected as a cause of OH.5
The 2018 European Society of Cardiology (ESC)
guidelines for the diagnosis and management of syn-
cope outline the evidence behind non-pharmacological
treatments (Table 2).36
A multidisciplinary team consisting of pharmacists,
nurses and medical personnel can positively impact man-
agement of this challenging condition in older adults.37
© 2018 The Society of Hospital Pharmacists of Australia

Orthostatic hypotension in older people
Pharmacological Management
Pharmacological treatments may be considered if OH per-
sists despite a trial of non-pharmacological management.
Fludrocortisone
Fludrocortisone acetate is a synthetic mineralocorticoid
with minimal glucocorticoid effects. It increases renal
sodium retention and expands plasma volume. After
oral administration, fludrocortisone is readily absorbed
and peak plasma levels are reached within 45 min with
a half-life of approximately 7 h.4 The effect of fludrocor-
tisone on plasma volume is transient. Its long-term effect
may be related to potentiation of the pressor effect of
angiotensin II and noradrenaline.15
The 2018 ESC guidelines recommend a dose of 0.1–
0.3 mg fludrocortisone once daily.36 Higher doses, rang-
ing from 0.2 mg twice daily to a maximum of 1 mg/day,
have been used but need to be used with caution and
under specialist supervision.2,18,20,21 Doses higher than
0.1–0.3 mg daily should be avoided in those with
hypoalbuminaemia and congestive heart failure.5 Higher
doses of fludrocortisone can result in supine hyperten-
sion and severe hypokalaemia. At higher doses, patients
may be at an increased risk of hypothalamic–pituitary–
adrenal axis suppression.13 Headaches can occur, espe-
cially while supine.4 Peripheral oedema is another com-
mon side effect of fludrocortisone. It is important to
review the concomitant use of medications, such as
diuretics, because volume depletion may render fludro-
cortisone ineffective.
Evidence for fludrocortisone is from two small obser-
vational studies (in combination with head-up sleeping)
and one double-blind trial in 60 patients.36 The observa-
tional studies demonstrated haemodynamic benefit. In
the trial, treated patients were less symptomatic with a
higher BP. The quality of evidence is moderate and fur-
ther research is likely to have an important effect on the
estimate of benefit.36 The 2018 ESC guidelines conclude
that fludrocortisone should be used when OH symp-
toms persist.36
Midodrine
Midodrine is a peripherally acting selective a1-adreno-
ceptor agonist that stimulates arterial and venous
adrenoceptors. Midodrine increases BP via vasoconstric-
tion.4 Midodrine is a useful addition in patients with
chronic autonomic failure.3,36,38 It may be preferred over
fludrocortisone for patients with OH and pre-existing
supine hypertension or heart failure, because it does not
produce excessive fluid retention.13,15 Vasoconstrictors
such as midodrine are ineffective when plasma volume
is reduced.16
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487
Midodrine does not cross the blood–brain barrier and
does not increase heart rate.15 It is a prodrug that is
rapidly converted to desglymidodrine, which has a
short half-life and a duration of action of approximately
3–4 h.13 Midodrine is excreted mainly in urine.15 Given
the short half-life of midodrine, the dosing schedule is
typically three times a day, with the first dose taken half
an hour prior to mobilisation in the morning. Patients
should be instructed to take the last dose at least 4–5 h
before bedtime to avoid supine hypertension, which
occurs in 25% of users.5,13 Doses of midodrine typically
start at 2.5 mg once or twice per day, increased as
required to 10 mg three times a day.5 The manufacturer
recommends avoiding the use of midodrine in severe
renal impairment (estimated glomerular filtration rate
<30 mL/min per 1.73 m2), but the Renal Drug Hand-
book recommends it for treatment of dialysis-related
OH.39
Side effects of midodrine include supine hyperten-
sion, piloerection (goose bumps), scalp tingling, urinary
urgency or retention and, rarely, headaches. Caution
should be exercised when using midodrine in patients
with acute kidney injury, liver disease, severe heart dis-
ease, thyrotoxicosis and phaeochromocytoma.5,14 Occa-
sional side effects such as insomnia and irritability have
also been reported.14 Some patients’ OH worsens on
midodrine and the mechanism is thought to be adreno-
ceptor desensitisation.39
Evidence for the use of midodrine is conflicting. A
meta-analysis in 2014 suggested a lack of evidence.39
This is in contrast with other reviews that have reported
that the use of midodrine in neurogenic OH does reach
a strong recommendation level.40–42 According to 2018
ESC guidelines,36 midodrine is not helpful in all
patients, but it is very useful in some. The desirable
effects of midodrine outweigh the undesirable effects in
patients with chronic autonomic failure.36 Midodrine
certainly increases BP in both the supine and upright
positions and ameliorates the symptoms of OH. Mido-
drine is not marketed in Australia, but is available via
the Therapeutic Goods Administration (TGA) Special
Access Scheme.
Combination therapy with fludrocortisone and mido-
drine, using lower doses of both agents (due to syner-
gistic effects), may be beneficial in refractory
patients.15,18,38,43
Pyridostigmine
Pyridostigmine is a cholinesterase inhibitor that
improves neurotransmission at acetylcholine-mediated
neurons of the autonomic nervous system.44 Pyridostig-
mine improves OH and total peripheral resistance with-
out aggravating supine hypertension.21 Because the
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488 G. P. Godbole and B. Aggarwal

Table 3 Other medications with potential utility in orthostatic hypotension

Medication Mechanism of action Comment Adverse events and precautions

Atomoxetine Noradrenaline reuptake inhibitor
that exerts a vasopressor effect
Domperidone Dopamine receptor antagonist
Mirabegron b3-Adrenoceptor agonist
Octreotide Synthetic somatostatin analogue
that constricts splanchnic
circulation and reduces venous
pooling
Erythropoietin Expands red cell mass and
increases total blood volume;2
also appears to have a
vasoconstrictor effect because of
its effects on NO production34
NSAIDs Inhibit the vasodilatory effects of
prostaglandins and increase BP in
some patients with OH13
Caffeine Adenosine receptor blocker that
inhibits adenosine-induced
vasodilatation
Desmopressin Vasopressin analogue that increases
water reabsorption and reduces
nocturia
Used for management of ADHD,
but a proof-of-concept study
comparing atomoxetine with
midodrine in patients with OH
reported that it increased
standing SBP more than
midodrine;5 further trials are
required before considering this
agent for OH treatment
Anecdotal evidence for use in
treating OH that occurs after
initiating the dopamine agonist
apomorphine in people with
Parkinson’s disease56,57
Used for treatment of overactive
bladder but, given its stimulatory
effect on the cardiovascular
system, it has been considered for
OH5
Can be effective when other agents
fail, but does not have robust
evidence to support its use; its
use is limited by side effects and
the need for subcutaneous
administration
Has been shown to be effective in
patients with anaemia and
autonomic dysfunction
Lacks a strong evidence base for
OH;2 use with caution in older
people due to the risk of adverse
effects
Has been used in doses of 200 mg
in the form of brewed coffee or
tablets; may attenuate OH
symptoms in some patients18 but
evidence for its use is mixed13
Efficacy is uncertain and clinical
utility is limited by side
effects3,13,30
Insomnia, nausea, vomiting,
weakness and hepatotoxicity
Hypertension may develop in
10% of patients
Can cause QT prolongation and is
associated with an increased
risk of ventricular
tachyarrythmias and sudden
cardiac death in patients with
pre-existing cardiac disease
There is a risk of severe
hypertension5
Abdominal pain, nausea,
hyperglycaemia
Use with caution in patients with
T2DM because they are more
prone to side effects and rarely
tolerate this drug.4,13,15
Supine hypertension, stroke,
myocardial infarction13,18
Gastrointestinal bleeds, renal
impairment4
Insomnia (therefore should be
taken in the morning)
Hyponatraemia

ADHD = attention deficit hyperactivity disorder; BP = blood pressure; NO = nitric oxide; NSAIDs = non-steroidal anti-inflammatory
drugs; OH = orthostatic hypotension; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus.

pressor effect of pyridostigmine is modest, it is adequate
in patients with mild to moderate OH of neurogenic ori-
gin.45 The usual starting dose of pyridostigmine is
30 mg twice a day, which can be slowly titrated up to
90 mg three times a day.34 Side effects include nausea,
diarrhoea, urinary urgency, diaphoresis, hyper salivation
and fasciculations.13,34,44 Contraindications include
hypersensitivity to bromides or pyridostigmine and uri-
nary obstruction.46
Pyridostigmine has been shown to improve OH com-
pared with placebo.47 However, there is a need for
robust studies in older people to confirm its effective-
ness and tolerability in this population. A randomised
trial comparing pyridostigmine to fludrocortisone in the

Journal of Pharmacy Practice and Research (2018) 48, 483–491 © 2018 The Society of Hospital Pharmacists of Australia

Orthostatic hypotension in older people
treatment of OH in Parkinson’s disease concluded that
pyridostigmine was inferior to fludrocortisone.44 The
evidence supporting the use of pyridostigmine is con-
flicting at best, and hence the recommendation for its
use is weak.45,48
Droxidopa
Droxidopa is a synthetic amino acid precursor that is
converted by aromatic L-amino acid decarboxylase into
noradrenaline. Droxidopa acts to increase levels of nora-
drenaline in postganglionic sympathetic neurons, lead-
ing to increased stimulation of adrenoceptors and hence
increased BP.49 Droxidopa has a short half-life of 2–3 h
and should be avoided within 5 h of bedtime to avoid
supine hypertension.3
Evidence for droxidopa is promising, but long-term
data on its use are limited.40 Droxidopa has been used
in Japan since 1989, but has only recently been
approved for OH in the US and UK. It is not yet
approved in Australia, but can be obtained under the
TGA Special Access Scheme.
Possible side effects of droxidopa include hyperten-
sion, headache, dizziness, nausea, falls and urinary tract
infections.50 Syncope and dizziness have also been
reported, although systematic post-marketing studies to
define the rate of adverse events in clinical practice are
not available.51 A systematic review exploring the effect
of droxidopa compared with midodrine on standing BP
and orthostatic tolerance in adults with neurogenic
orthostatic hypotension is underway.52 Because the evi-
dence for droxidopa is limited, and due to a lack of
long-term data on safety, it has not been included in the
current ESC guidelines.
Other Medications
Numerous other medications have been considered for
the management of OH and may be useful in selected
patients. These are summarised in Table 3.
SUPINE HYPERTENSION WITH OH
Patients with autonomic failure often experience both
neurogenic OH and severe nocturnal supine hyper-
tension.14,53,54 This is a clinical dilemma for clinicians
because they must balance the risk of chronic high
BP with the risk of falls and increased morbidity
associated with OH.53 In these cases, fludrocortisone
should be limited and using evening short-acting
antihypertensive agents may be considered. However,
the long-term cardiovascular risk associated with
supine hypertension is not well known, and the
© 2018 The Society of Hospital Pharmacists of Australia
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489
decision to treat should be tailored to individual
patient needs.
If the patient is not at high risk of falls, and BP-lower-
ing therapy is warranted, angiotensin-converting
enzyme inhibitors (short-acting agents such as capto-
pril), angiotensin receptor blockers (such as losartan)
and calcium channel blockers (such as nifedipine) are
preferred. The use of glyceryl trinitrate (GTN) patches
(with removal 1 h before rising), hydralazine and
minoxidil has been investigated.3 Although the use of
GTN patches is fairly common, the evidence supporting
their use is limited. Pindolol may be effective due to its
limited effect on daytime OH (because of its intrinsic
sympathomimetic effect), but robust evidence is lack-
ing.3 In general, 24-h ambulatory BP monitoring should
be performed first, and night-time administration of
antihypertensive doses is preferred, even if the patient is
treated for ischemic heart disease or heart failure.
Diuretics and beta-blockers should be avoided, if possi-
ble, because they are associated with OH and falls.30
CONCLUSION
The evidence to support the effectiveness of pharmaco-
logical measures in older people with OH is limited.
Non-pharmacological strategies, including discontinua-
tion or reduction of vasoactive drugs, need to be
explored before choosing medications to treat OH.36
Drugs generally recommended for OH treatment are flu-
drocortisone and/or midodrine, with due consideration
of their precautions. There are systematic reviews cur-
rently underway55 that will hopefully provide more
robust evidence. Meanwhile, it is important to tailor
treatment based on individual presentation and needs.
Conflict of interests statement
The authors declare that they have no conflicts of
interest.
REFERENCES
1 Shibao C, Grijalva CG, Raj SR, Biaggioni I, Griffin MR. Orthostatic
hypotension-related hospitalizations in the United States. Am J
Med 2007; 120: 975–80.
2 Mader SL. Identification and management of orthostatic
hypotension in older and medically complex patients. Expert Rev
Cardiovasc Ther 2012; 10: 387–95.
3 Chisholm P, Anpalahan M. Orthostatic hypotension:
pathophysiology, assessment, treatment and the paradox of supine
hypertension. Intern Med J 2017; 47: 370–9.
Journal of Pharmacy Practice and Research (2018) 48, 483–491

490
4 Lahrmann H, Cortelli P, Hilz M, Mathias C, Struhal W, Tassinari
M. EFNS guidelines on the diagnosis and management of
orthostatic hypotension. Eur J Neurol 2006; 13: 930–6.
5 Frith J, Parry SW. New horizons in orthostatic hypotension. Age
Ageing 2017; 46: 168–74.
6 Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E,
Biaggioni I, et al. Consensus statement on the definition of
orthostatic hypotension, neurally mediated syncope and the
postural tachycardia syndrome. Clin Auton Res 2011; 21: 69–72.
7 Wieling W, Schatz IJ. The consensus statement on the definition of
orthostatic hypotension: a revisit after 13 years. J Hypertens 2009;
27: 935–8.
8 Gibbons CH, Freeman R. Delayed orthostatic hypotension a
frequent cause of orthostatic intolerance. Neurology 2006; 67: 28–32.
9 Hiitola P, Enlund H, Kettunen R, Sulkava R, Hartikainen S.
Postural changes in blood pressure and the prevalence of
orthostatic hypotension among home-dwelling elderly aged
75 years or older. J Hum Hypertens 2009; 23: 33–9.
10 Veronese N, De Rui M, Bolzetta F, Zambon S, Corti MC, Baggio
G, et al. Orthostatic changes in blood pressure and mortality in
the elderly: The Pro.V.A Study. Am J Hypertens 2015;28:1248–56.
11 Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS.
Orthostatic hypotension in older adults. The Cardiovascular
Health Study. CHS Collaborative Research Group. Hypertension
1992; 19: 508–19.
12 Kuritzky L, Espay AJ, Gelblum J, Payne R, Dietrich E. Diagnosing
and treating neurogenic orthostatic hypotension in primary care.
Postgrad Med 2015; 127: 702–15.
13 Jones PK, Shaw BH, Raj SR. Orthostatic hypotension: managing a
difficult problem. Expert Rev Cardiovasc Ther 2015; 13: 1263–76.
14 Pavy-Le Traon A. How to manage a patient with orthostatic
hypotension. Teaching course 13. In: Proceedings of the 3rd
Congress of the European Academy of Neurology, 2017, June 24–
27; Amsterdam, The Netherlands. Available from https://www.ea
n.org/amsterdam2017/fileadmin/user_upload/TC13_02_Pavy-Le_
Traon.pdf. Accessed 10 July 2018.
15 Shibao C, Lipsitz LA, Biaggioni I. ASH position paper: evaluation
and treatment of orthostatic hypotension. J Clin Hypertens 2013;
15: 147–53.
16 Wolters FJ, Mattace-Raso FUS, Koudstaal PJ, Hofman A, Ikram
MA; Heart Brain Connection Collaborative Research Group.
Orthostatic hypotension and the long-term risk of dementia: a
population-based study. PLoS Med 2016; 13: e1002143.
17 Verwoert GC, Mattace-Raso FU, Hofman A, Heeringa J, Stricker
BH, Breteler M, et al. Orthostatic hypotension and risk of
cardiovascular disease in elderly people: the Rotterdam study. J
Am Geriatr Soc 2008; 56: 1816–20.
18 Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly:
diagnosis and treatment. Am J Med 2007; 120: 841–7.
19 Robertson D. The pathophysiology and diagnosis of orthostatic
hypotension. Clin Auton Res 2008; 18(Suppl 1): S2–7.
20 Freeman R. Neurogenic orthostatic hypotension. N Engl J Med
2008; 358: 615–24.
21 Figueroa JJ, Basford JR, Low PA. Preventing and treating
orthostatic hypotension: as easy as A, B, C. Cleve Clin J Med 2010;
77: 298–306.
22 Freidenberg DL, Shaffer LE, Macalester S, Fannin EA. Orthostatic
hypotension in patients with dementia: clinical features and
response to treatment. Cogn Behav Neurol 2013; 26: 105–20.
Journal of Pharmacy Practice and Research (2018) 48, 483–491
20552335, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jppr.1484 by Iraq Hinari NPL, Wiley Online Library on [18/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
G. P. Godbole and B. Aggarwal
23 Fedorowski A, Melander O. Syndromes of orthostatic intolerance:
a hidden danger. J Gen Intern Med 2013; 273: 322–35.
24 Kamaruzzaman S, Watt H, Carson C, Ebrahim S. The association
between orthostatic hypotension and medication use in the British
Women’s Heart and Health Study. Age Ageing 2009; 39: 51–6.
25 Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, et al.
Norepinephrine transporter blockade with atomoxetine induces
hypertension in patients with impaired autonomic function.
Hypertension 2007; 50: 47–53.
26 Gugger JJ. Antipsychotic pharmacotherapy and orthostatic
hypotension. CNS Drugs 2011; 25: 659–71.
27 Psychotropic drugs. Comparison of adverse effects of some
antipsychotics. In: Australian medicines handbook. Adelaide:
Australian Medicines Handbook Pty Ltd; 2018. p. 843.
28 Poon I, Braun U. High prevalence of orthostatic hypotension and
its correlation with potentially causative medications among
elderly veterans. J Clin Pharm Ther 2005; 30: 173–8.
29 Weir MR, Weber MA, Neutel JM, Vendetti J, Michelson EL, Wang
RY. Efficacy of candesartan cilexetil as add-on therapy in
hypertensive patients uncontrolled on background therapy: a
clinical experience trial. Am J Hypertens 2001; 14: 567–72.
30 Ricci F, De Caterina R, Fedorowski A. Orthostatic hypotension:
epidemiology, prognosis, and treatment. J Am Coll Cardiol 2015;
66: 848–60.
31 Hartog L, Kleefstra N, Luigies R, Rooij S, Bilo H, Hateren K. The
clinical relevance of orthostatic hypotension in elderly patients.
Geriatr Gerontol Int 2017; 17: 1881–5.
32 Logan A, Marsden J, Freeman J, Kent B. Effectiveness of non-
pharmacological interventions in treating orthostatic hypotension
in the elderly and people with a neurological condition: a
systematic review protocol. JBI Database System Rev Implement Rep
2017; 15: 948–60.
33 Gillis DJ, Wouda M, Hjeltnes N. Non-pharmacological
management of orthostatic hypotension after spinal cord injury: a
critical review of the literature. Spinal Cord 2008; 46: 652–9.
34 Kanjwal K, George A, Figueredo VM, Grubb BP. Orthostatic
hypotension: definition, diagnosis and management. J Cardiovasc
Med 2015; 16: 75–81.
35 Biaggioni I. New developments in the management of neurogenic
orthostatic hypotension. Curr Cardiol Rep 2014; 16: 542.
36 Brignole M, Moya A, de Lange FJ, Deharo J-C, Elliott PM,
Fanciulli A, et al. 2018 ESC Guidelines for the diagnosis and
management of syncope. Eur Heart J 2018; 39: 1883–948.
37 Holden K. Pharmacist and nurse combine skills to assess people
who fall. Clin Pharmacist 2009; 1: 235.
38 Kaufmann H, Brannan T, Krakoff L, Yahr M, Mandeli J. Treatment
of orthostatic hypotension due to autonomic failure with a
peripheral alpha adrenergic agonist (midodrine). Neurology 1988;
38: 951–6.
39 Parsaik AK, Singh B, Altayar O, Mascarenhas SS, Singh SK, Erwin
PJ, et al. Midodrine for orthostatic hypotension: a systematic
review and meta-analysis of clinical trials. J Gen Intern Med 2013;
28: 1496–503.
40 Eschlb€ ock S, Wenning G, Fanciulli A. Evidence-based treatment of
neurogenic orthostatic hypotension and related symptoms. J
Neural Transm 2017; 124: 1567–605.
41 Ong A, Myint P, Shepstone L, Potter J. A systematic review of the
pharmacological management of orthostatic hypotension. Int J Clin
Pract 2013; 67: 633–46.
© 2018 The Society of Hospital Pharmacists of Australia
 20552335, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jppr.1484 by Iraq Hinari NPL, Wiley Online Library on [18/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Orthostatic hypotension in older people 491

42 Izcovich A, Malla CG, Manzotti M, Catalano HN, Guyatt G. 53 Ahmed A, Grubb B, Zaman L, Kanjwal K. Syndrome of supine
Midodrine for orthostatic hypotension and recurrent reflex hypertension with orthostatic hypotension. A nightmare for
syncope. A systematic review. Neurology 2014; 83: 1170–7. physicians. J Innovat Cardiac Rhythm Manage 2016; 7: 2285–8.
43 Logan IC, Witham MD. Efficacy of treatments for orthostatic 54 Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R,
hypotension: a systematic review. Age Ageing 2012; 41: 587–94. Isaacson S, et al. The recommendations of a consensus panel for
44 Schreglmann S, B€ uchele F, Sommerauer M, Epprecht L, K€agi G, the screening, diagnosis, and treatment of neurogenic orthostatic
H€agele-Link S, et al. Pyridostigmine bromide versus hypotension and associated supine hypertension. J Neurol 2017;
fludrocortisone in the treatment of orthostatic hypotension in 264: 1567–82.
Parkinson’s disease–a randomized controlled trial. Eur J Neurol 55 Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH, Raj SR,
2017; 24: 545–51. et al. Fludrocortisone for orthostatic hypotension [protocol].
45 Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Cochrane Database Syst Rev 2017; 12: CD012868.
Hines S, et al. Pyridostigmine treatment trial in neurogenic 56 Bacchi S, Chim I, Kramer P, Postuma R. Domperidone for
orthostatic hypotension. Arch Neurol 2006; 63: 513–18. hypotension in Parkinson’s disease: a systematic review. J
46 Lanier J, Mote M, Clay E. Evaluation and management of Parkinsons Dis 2017; 7: 603–17.
orthostatic hypotension. Am Fam Physician 2011; 84: 527–36. 57 Lang A. Acute orthostatic hypotension when starting dopamine
47 Goldstein DS, Pechnik S, Holmes C, Eldadah B, Sharabi Y. agonist therapy in Parkinson’s disease: the role of dopamine
Association between supine hypertension and orthostatic therapy. Arch Neurol 2001; 58: 835.
hypotension in autonomic failure. Hypertension 2003; 42:
136–42. Received: 17 May 2018
48 Shibao C, Okamoto LE, Gamboa A, Yu C, Raj SR, Robertson D, Revised version received: 8 July 2018
et al. Comparative efficacy of yohimbine against pyridostigmine Accepted: 12 July 2018
for the treatment of orthostatic hypotension in autonomic failure.
Hypertension 2010; 56: 847–51. This activity has been
49 Keating GM. Droxidopa: a review of its use in symptomatic accredited for 0.5 hours
neurogenic orthostatic hypotension. Drugs 2015; 75: 197–206. of Group 1 CPD activity
50 Isaacson S, Vernino S, Ziemann A, Rowse G, Kalu U, White W. (or 0.5 CPD credits) suit-
able for inclusion in an
Longterm safety of droxidopa in patients with symptomatic
individual pharmacist’s
neurogenic orthostatic hypotension. J Am Soc Hypertens 2016; 10: CPD plan, which can be
755–62. converted to 0.5 hours
51 Kaufmann H, Norcliffe-Kaufmann L, Palma J-A. Droxidopa in of Group 2 CPD (or 1
neurogenic orthostatic hypotension. Expert Rev Cardiovasc Ther CPD credit) upon suc-
2015; 13: 875–91. cessful completion of
the relevant assessment
52 Patrick K, Martin T. Effectiveness of droxidopa compared to
activity. No:S2018/90.
midodrine in standing blood pressure and orthostatic tolerance in
adults with neurogenic orthostatic hypotension: a systematic
review protocol. JBI Database System Rev Implement Rep 2017; 15:
2287–94.

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