Fludrocortisone for the treatment of orthostatic hypotension

Review question

In people with orthostatic hypotension, does fludrocortisone prevent or reduce a symptomatic drop in blood pressure that occurs with changes in position (for example, from sitting to standing) and does it have unwanted effects?


Orthostatic, or postural, hypotension is a condition in which blood pressure falls when moving from a seated or lying flat position to a standing position. Regular, reproducible symptomatic postural hypotension is an abnormal bodily response.

Orthostatic hypotension can be due to the heart failing to supply enough blood to the brain after a change in position. It can also stem from failures in blood vessel response to a change in position, for which there are many causes. Medications, dehydration, poor physical health and age all contribute to the problem. It is more common among people older than 65 and increases with age.

Symptoms include dizziness, lightheadedness and feeling faint. Some people have more general complaints such as weakness, fatigue, headache, visual blurring, trouble thinking, leg buckling, neck pain, breathlessness or chest pain. Some episodes of postural hypotension result in a faint, fall or 'black-out'. Symptoms decrease when blood pressure returns to normal, typically when the person sits, lies or, occasionally, falls down.

Fludrocortisone acetate is a man-made steroid that increases blood volume and improves the ability of blood vessels to respond to changes in position. Fludrocortisone is taken by mouth. It has also been associated with high blood pressure, swelling, congestive heart failure, low potassium (a blood salt), headache, sleeplessness and increased sweating. Other common medications for postural hypotension include midodrine and droxidopa.

Because postural hypotension results from many underlying diseases and conditions, it is important to understand the effect of fludrocortisone depending upon the underlying physical cause (heart pumping action or blood vessel reaction), by other underlying disease (Parkinson disease, diabetes, etc.) and by age. In this way, we can better understand whether different groups of people will be helped or harmed by using this medication.

We reviewed all the evidence about the effects of use of fludrocortisone in people with orthostatic hypotension.

Search date

The evidence is up to date to 11 November 2019.

Study characteristics

After in-depth screening of the scientific literature, we included 13 studies involving 513 participants. Only three studies used the most rigorous research design (randomized controlled trial [RCT]). Additionally, two non-RCTs filled gaps in the evidence. The randomized studies were small (a total of 28) and short-term (lasting three weeks or less). The randomized studies found that fludrocortisone reduced blood pressure drop compared to placebo (an inactive medication) in people with severe diabetic neuropathy, and compared to a medication called pyridostigmine when used in people with Parkinson disease. Among people with Parkinson disease, overall orthostatic symptoms were unchanged when fludrocortisone was compared to pyridostigmine but symptoms were reduced by both fludrocortisone and domperidone (an alternative medication) when compared. Side effects seen in these studies were minimal.

Study funding sources

Of the five studies that offered the best available evidence, two were at least partially funded by research foundations (such as the Dysautonomia Foundation), one had fludrocortisone tablets provided by the pharmaceutical company, and two did not report on funding.

Key results and certainty of the evidence

Based on considerable limitations in the available evidence, we cannot draw firm conclusions on the use of fludrocortisone for orthostatic hypotension in people with diabetes or Parkinson disease. The available evidence on blood pressure drop, orthostatic symptoms and adverse events in people with diabetes or Parkinson disease was very low-certainty. We still need more and better information about long-term use and about the effects of this medication among people with diseases besides Parkinson disease and diabetes.

Authors' conclusions: 

The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.

Read the full abstract...

Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.


To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.

Search strategy: 

We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.

Selection criteria: 

We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.

Data collection and analysis: 

We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.

Main results: 

We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs.

We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants).

For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal.

Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.