Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – eliminate aggravating factors and institute lifestyle changes

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ACUTE
|
all patients
1st line – 

eliminate aggravating factors and institute lifestyle changes

Medications that induce or aggravate orthostatic hypotension (OH; e.g., alpha-blockers, central sympatholytics such as tizanidine or methyldopa, tricyclic antidepressants, phosphodiesterase-5 inhibitors, beta-blockers) should be carefully reviewed and eliminated, if appropriate.[15][18][38]​​​​ As ‘bladder-selective’ alpha-blockers, such as tamsulosin, can aggravate OH in older men, this in turn may increase the risk of hip fracture.[42][43]

Hypertension is a risk factor for OH, and both conditions commonly co-exist in older patients. Although certain antihypertensive agents can trigger or worsen OH, complete withdrawal of antihypertensives is not appropriate as this will lead to pressure diuresis and worsening of OH. One meta-analysis found that effective antihypertensive treatment is possible without worsening of OH.[44] Judicious use of antihypertensives (e.g., ACE inhibitors, angiotensin-II receptor antagonists) and avoiding agents likely to cause OH (e.g., alpha-blockers, central sympatholytics, beta-blockers) is recommended.

Patients should first sit when going from supine to standing. Straining during bowel movements or performing Valsalva-like manoeuvres should be avoided. Eating frequent, small meals is often effective in lessening postprandial hypotension. Patients should be aware that hot environments may worsen OH.

Physical counter-manoeuvres when upright, such as leg-crossing, standing on tiptoes, and muscle-tensing, enhance orthostatic tolerance. Custom-made, full-length elastic stockings can be useful in preventing pooling in the lower extremeties, but can be difficult to use. An abdominal binder may be as effective as a vasopressor, and can be tried first.[45][46]

Patients should liberalise their dietary salt intake or use sodium chloride tablets with each meal and drink at least 2 litres of water a day.[29]​ Tilting the head of the bed up during the night, by inserting blocks 15-22 cm (6-9 inches) high under the headposts, reduces overnight sodium and water excretion by the kidney and lessens OH in the morning. Another effective strategy is to rapidly drink 500 mL (16 oz) of tap water, as a fluid bolus, in 3-4 minutes. This can be used as a rescue measure for patients who are symptomatic on standing, and takes effect within 5-10 minutes, peaking at 30 minutes. This is thought to be a sympathetic reflex induced by the hypotonicity of the water rather than a volume effect.[15]

Consider – short-acting pressor or droxidopa

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ACUTE
|
all patients
Consider – 

short-acting pressor or droxidopa

Additional treatment recommended for SOME patients in selected patient group

When non-pharmacological measures are not sufficient to alleviate symptoms, a short-acting pressor or droxidopa can be used.[38][50][51][53]​​​ Only two medications are approved for the treatment of orthostatic hypotension (OH): midodrine and droxidopa.

Vasoconstrictor agents, such as the selective alpha-1-adrenoreceptor agonist midodrine, increase blood pressure and improve symptoms of OH.[38]​ Adverse effects of midodrine include pilomotor reactions, pruritus, supine hypertension, and urinary retention.[49]

Droxidopa, a noradrenaline prodrug, is converted to noradrenaline in the body by the same enzyme that converts levodopa to dopamine.[53]​ It increases blood pressure, with a peak effect about 3 hours after administration, and improves symptoms associated with OH. It has been approved for the treatment of neurogenic OH, based upon randomised controlled trials demonstrating symptom improvement after 1 week of treatment.[54][55]​ A post-marketing study to determine persistence of effects is ongoing.[56]​ Droxidopa should be taken upon arising in the morning, at midday, and late afternoon at least 3 hours prior to bedtime to reduce the potential for supine hypertension. However, many patients can miss out the late afternoon dose. It may not be available in countries outside the US.

Pyridostigmine, an acetylcholinesterase inhibitor, has modest pressor effects but can help some patients with mild-to-moderate OH. It is often used in combination with midodrine.[50]

The noradrenaline-reuptake inhibitor atomoxetine can acutely improve upright blood pressure and ameliorate symptoms in some patients, but long-term efficacy has not been demonstrated.[51][52]

Pressor agents are best given on an as-required basis, within the prescribed daily frequencies, taken 30-45 minutes before upright activity or meals (according to the precipitating factor for an individual patient), and their effect lasts for 2-3 hours.[38]​ They should be avoided before bed.

Primary options

midodrine: 10 mg orally three times daily

OR

droxidopa: 100-600 mg orally three times daily

Secondary options

pyridostigmine: consult specialist for guidance on dose

OR

atomoxetine: consult specialist for guidance on dose

Consider – mineralocorticoid therapy

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ACUTE
|
all patients
|
absence of hypertension or heart failure
Consider – 

mineralocorticoid therapy

Additional treatment recommended for SOME patients in selected patient group

In non-hypertensive patients in whom non-pharmacological measures do not achieve the desired result, consideration can be given to treatment with fludrocortisone (a synthetic mineralocorticoid).[38]​ It is generally contraindicated in patients with heart failure - a common comorbidity of patients with orthostatic hypotension (OH).

When combined with a high salt intake, fludrocortisone raises blood pressure.[57]​ Evidence for fludrocortisone is, however, limited to small randomised controlled trials (of people with diabetes or Parkinson’s disease) and observational studies.[58]​ Dietary salt can be increased or sodium chloride tablets can be taken. Water intake should be at least 2 litres each day.[29]

Potassium supplementation may be needed, because fludrocortisone increases renal potassium excretion. Fludrocortisone should be used with extreme caution as it results in hypertension when supine, promotes cardiac fibrosis, and may accelerate progression of renal deterioration.[59]

Primary options

fludrocortisone: 0.1 to 0.2 mg orally once daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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