The Orthostatic Intolerance (OI) Centerw
Medical Care for OI
Subsection: Medications
• Overview
• Common Meds
• Other Factors to Consider
• Full List By What They Do
• Hyperadrenergic POTS
• References
• Overview
• Common Meds
• Other Factors to Consider
• Full List By What They Do
• Hyperadrenergic POTS
• References
Common Medications
There are a number of medications that are used to improve orthostatic intolerance symptoms that are included in reference articles on orthostatic intolerance (OI), orthostatic hypotension (OH), neurally-mediated orthostatic hypotension (NMH)and postural orthostatic tachycardia syndrome (POTS).1-13
Commonly Used Medications for Orthostatic Symptoms and Conditions
- Beta-blockers
- Fludrocortisone
- Midodrine
- Pyridostigmine
- SSRI/SSNRI
- Stimulants
| Drug Name | Beta Blockers - Atenolol, Metoprolol, Labetalol, Pindolol |
|---|---|
| What it works on | • Low dose beta blockers - prevent excessive vasodilation of arteries that occur with syncope and prevent excessive stimulation of the ventricular receptors.4 They interfere with catecholamine-mediated increase in heart rate. • For POTS-They interfere with the force of heart contraction, to block initiation of NHM reflex; may prevent Epi-induced vasodilatation2 |
| Usual dose | • Atenolol 25 mg. Less is more8 |
| How to start | |
| Caveats | • Resting HR should be no lower than 50 beats per minute. Less is more8 |
| Monitor | |
| Side Effects | • Fatigue, LH, decreased mood, cough/wheeze in asthmatics2 |
| Drug Name | Fludrocortisone (Florinef) |
|---|---|
| What it works on | • This is a synthetic mineralocorticoid. • It can improve blood pressure because it increases the plasma volume of blood and increases the blood vessels sensitivity to get smaller (constrict) more readily to epinephrine and norepinephrine (NE).(also called vascular alpha-adrenoceptor sensitivity).1,3 • It acts in the kidney to hold on to sodium (salt) in the body. It may help blood vessels 1 • The body holds on to sodium at the expense of losing potassium in the urine. • It results in predictable increases in BP. It's well-tolerated, stimulates the arterial and venous systems, and does not increase heart rate. With neurogenic OH, it can increase the systolic BP about 22 mmHg. |
| Usual dose | • There are different opinions about how much the usual dose should be and what is needed. • Dr. Freeman: 0.05-0.3 mg daily5 • Drs. Figueroa & Low: 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension3,7 • Dr. Medow: Most require 0.3 to 0.4 mg per day for optimal control.4 • Dr. Rowe: Rarely uses more than 0.2 mg/day. Higher doses are also associated with electrolyte problems.1 |
| How to start | Start Low Approach: • Dr. Medow's approach: Start at 0.1 mg/da and increase at 1 to 2 week intervals to a total dose of 1 mg/;d. Dr. Medow's experience is that 0.3 to 0.4 mg per day may be needed for optimal control.4 Start Low Approach: • Dr. Rowe: Start at 0.05 mg/day and increase by 0.05 mg every 2 weeks if needed to a total dose of 0.2 mg/;d. Taken From Dr. Peter Rowe's General Information Brochure, with permission:1 • Because the optimal dose can vary considerably, we suggest that those who use Florinef begin with a low dose and increase it gradually. We recommend beginning with a week of increasing salt and fluid before starting on Florinef to ensure better tolerance of the drug. Once you are ready to start, begin with ½ tablet per day for a week, then increase to a full 0.1 mg tablet daily. |
| Caveats | • If the person gains 3 to 5 pounds (1.2–2.3 kg) and develops mild edema in the legs/feet, it can be assumed that the the plasma volume has expanded adequately.3 • Issues have been raised about its value in children 14,4, 7 • With long term use, plasma volume returns to normal but BP effect remains130 4,5, 14 • Be sure to drink lots of water. This will reduce the chance of getting an increased blood sodium level. From Dr. Peter Rowe's General Information Brochure:1 • Some individuals complain of headache after Florinef and some develop worse CFS symptoms (more lightheadedness or fatigue), abdominal discomfort of a new type or severity, new chest discomfort, or tearfulness and depression. • Optimal frequency to check the electrolytes has not been established. • If BP increases over time, lower dose of Florinef. • Drug interactions: possibly with warfarin. They may need substantial increase in dose. |
| Monitor |
• At higher doses, supine hypertension (high blood pressure when lying down) and hypokalemia (low potassium in the blood) are very common.3,7 |
| Side Effects | • Headache – is the more commonly noted side effect. It's more common in younger patients and those with milder disease. 4
• Fluid Retention (holding on to fluid and developing swelling in the feet and other parts of the body): Fludrocortisone should not be used in people with congestive heart failure and chronic renal failure.3 |
| Drug Name | Midodrine(ProAmatine) |
|---|---|
| What it works on | • Causes blood vessels to constrict, get tighter, narrower. (also called vasopressor,or vasoconstrictor, α1-adrenoreceptor agonist,sympathomimetic.) This lowers the amount of blood that can pool in the abdomen and legs. It shifts the blood into the center of the body where you want it, in the heart & lungs.1, 3 • It causes predictable increases in BP3 • It has been shown to increase standing systolic blood pressure, reduce orthostatic lightheadedness, and increases standing and walking time. 3, 5 • Improves presyncopal prodromal symptoms, energy level, feelings of depression, and standing time with only mild side effects20 • In neurogenic OH – it can increase systolic BP an average of 22 mmHg3, 19 |
| Usual dose | • 2.5 mg – 10 mg 2-4 times a day.5 • A common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day.3 • Start at 2.5 at breakfast and lunch, then increase by 2.5 until reach 30, usually 3 times a day.x • A conservative starting dose for midodrine is 2.5 mg three times daily to ensure that the dose is tolerated. The first dose should be taken upon awakening in the morning, then 4 hours later, and then 4 hours after that (e.g., 8AM, 12N, 4PM). |
| How to start | Excerpt from Dr. Peter Rowe's General Information Brochure:1 A reasonable dose progression follows: |
| Caveats | • Giving a dose 15-20 minutes getting out of bed can help with early morning symptoms.10 • Vasoconstrictors like midodrine do not work when plasma volume is reduced.3 It's important to take enough fluids and salt to increase plasma volume. • To avoid nocturnal supine hypertension (high blood pressure when lying down at night) -, doses should not be taken after the mid-afternoon or at least the final dose should be at least 4 hours before bedtime.5 A dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg.3 • Midodrine and stimulants in combination (both taken each day) can lead to excessive blood pressure elevations. If both are to be taken (Concurrent use), it needs to be done cautiously and with frequent monitoring of blood pressure and effects on the person. Dr. Rowe notes that they generally attempt to stop stimulant medications before starting midodrine.1 Again, if your doctor recommends it, it should be done under close supervision by your physician. Blood pressure should be carefully monitored. |
| Monitor | • Midodrine’s main side effects are supine hypertension, scalp paresthesias (funny skin feelings), and pilomotor reactions (goose bumps).3 • Omit a dose if BP >= 180/110, supine or sitting.3,7 • Hypertensive swings can occur. The mechanism is severe hypotension (low blood pressure). People who have a short duration of midodrine effectiveness (4 hr) should take it more often – every 3 hours.5 |
| Side Effects | • The main side effects are: high blood pressure when lying down in 15-20%, itching (also called pruritis) in 10-15%, pins and needles sensation in 5-10%, urinary urgency/full bladder in 5%.
• Supine hypertension (high blood pressure when lying down)- reported to develop in 25%4 • The pins and needles sensation may be felt as scalp tingling, and the hair on the arms and neck standing on end. • These changes are signs that the drug is working, and are not reasons to discontinue the drug.1 • Adolescents and young adults with NMH and POTS should not be at risk for the same degree of high supine blood pressure as those with orthostatic hypotension (whose average age is closer to 50-60 years), but one needs to watch for this.1 |
| Drug Name | Pyridostigmine (Mestinon) |
|---|---|
| What it works on |
• This is an acetyl choline esterase inhibitor that improves ganglionic neurotransmission in the sympathetic baroreflex pathway.3 It does this by increasing the parasympathetic tone (and vagal tone).6 • It lowers the heart rate1, 6 and blunts the heart-rate response to changes in position.6 • The pathway in the body that it affects is activated mostly during standing. It improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension (high blood pressure when lying down).3 • The effect on blood pressure is modest, it is most adequate for use with people who have mild to moderate orthostatic hypotension.3 The effect can be increased if it is used with low doses of Midodrine. 5 mg • Lowers the heart rate1 • Good results in POTS secondary to viral infection and autoimmune disorders like lupus or Sjögren's Syndrome.17, 183, 10 • Use alone or in combination with low dose propranolol3 • People with POTS due the following are thought to do well with it: › POTS that develops after a viral infection 3, 10 › POTS with autoimmune disorders like lupus or Sjögren's Syndrome.3, 10 › to paraneoplastic condition, symptoms usually resolve after treatment of the cancer10 › hyperadrenergic POTS6 |
| Usual dose | • 30-60 mg TID5 • Start at 30 mg BID and titrate up to 60-90 mg three times a day if needed10 • Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day3 • Mestinon Timespan, a 180-mg slow-release pyridostigmine tablet, can be taken once a day and may be a convenient alternative.3 |
| How to start | Excerpt from Dr. Peter Rowe's General Information Brochure:1 • Doses: In adolescents and adults with POTS and NMH, we have been using this dosage schedule, using the 60 mg pills or the 60 mg/5mL oral solution:1 » Day 1-3: 30 mg once daily 23 » Day 4-7: 30 mg twice daily (6-7 AM, 4PM) » Day 8-10: 60 mg AM, 30 mg PM » Day 11 onward: 60 mg twice daily • For those who have been home-bound, a more gradual increase in doses is warranted, and doses can be increased by 30 mg weekly. Some patients may benefit from lower doses of 30 mg once or twice daily, and if a good response is achieved at a low dose, there is no need to increase further. 1 |
| Caveats | • Effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension.21
• For those who have been home-bound, a more gradual increase in doses is warranted, and doses can be increased by 30 mg weekly. Some patients may benefit from lower doses of 30 mg once or twice daily, and if a good response is achieved at a low dose, there is no need to increase further. • Occasional patients benefit from a third dose during the day (morning, mid-day, bedtime), and one adolescent found that 45 mg in the morning, 30 mg at noon and 15 mg at bedtime was ideal for her. Some patients with CFS have been reported to do better on small doses of just 12.5-30 mg once daily.1 |
| Monitor | |
| Side Effects | • The main side effects are cholinergic (abdominal
Colic/stomach cramps, diarrhea). • Side effects: Mestinon is generally well tolerated, but the most common side effects are nervousness, muscle cramps or twitching, nausea, vomiting, or diarrhea, stomach cramps, increased saliva, anxiety, and watering eyes. Notify your physician if these are occurring, and if the side effects are more bothersome, stop the drug. • The most serious side effects are skin rash, itching, or hives, seizures, trouble breathing, slurred speech, confusion, or irregular heartbeat. • Because Mestinon can lower heart rate, it needs to be used with caution (and started at a low dose) in those whose heart rates at rest are in the 50-60 beats per minute range, and in those taking beta-blocker drugs (atenolol, propranolol, metoprolol, and others). • The drug can increase bronchial secretions in those with asthma, so it should be taken with caution in affected asthmatics.1 • Magnesium supplements can occasionally cause problems when taking Mestinon, so these should be stopped when Mestinon is started.1 |
| Drug Name | • The selective serotonin re-uptake inhibitor (SSRI) medications most commonly used for those with NMH or POTS are Zoloft, Prozac, and Lexapro, but others in this class of antidepressant medications are likely to work as well.1 • SSRI - See full list for all the names. Brands-Prozac, Celexa, Lexapro, Paxil, Zoloft • SNRI - See full list |
|---|---|
| What it works on | • The SSRI medications prevent the reuptake of serotonin at nerve terminals. This means they leave more serotonin available in the nerve. Serotonin can have a vasoconstricting effect on blood
vessels.1 • SSRI - are possibly more helpful with neurocardiogenic syncope 10 • SNRI - appear more useful with POTS10 |
| Usual dose | • The doses used to treat NMH or POTS are similar to those used for the treatment of depression; |
| How to start | Excerpt from Dr. Peter Rowe's General Information Brochure:1 • As with the other medications for NMH and POTS, it makes sense to start at a low dose and to increase gradually (allowing 2-4 weeks for the medication to begin working after a particular dose increase).1 • With Zoloft, for example, we usually begin with a dose of 12.5 - 25 mg per day, increasing to 50 mg per day if needed after 2-4 weeks, then adjusting upwards depending on the response.1 • With Lexapro, the starting dose is 5 mg per day for 2-4 weeks, then increasing to 10 mg per day if needed. Further gradual increases may be warranted after another month.1 |
| Caveats | Excerpt from Dr. Peter Rowe's General Information Brochure:1 • Some patients describe worse orthostatic intolerance (lightheadedness, fainting) or worse fatigue on the SSRIs. If these symptoms occur, we usually stop the drug. Other side effects that can occur include increased bruising, sweating, reduced libido, diarrhea or nausea, or insomnia.1 • These medications may be especially helpful in patients with increased anxiety or depressed mood, as their primary use is for treating these symptoms, but one does not need to have either anxiety or depression for the SSRIs to help with NMH or POTS. • One of the recent areas of concern about this class of medications has related to the rare but serious risk of suicide in the first 1-2 weeks after starting these medications. The evidence suggests that this risk is primarily seen in those who are severely depressed. In these individuals, who have suicidal thoughts but are too apathetic and sluggish to act upon them, the SSRI medications can have an early activating effect. As a result, patients can have improved energy for the first 1-2 weeks after starting the SSRI medications, but this improved energy occurs before their moods improve. Until mood improves, the individual who remains suicidal has the energy to act upon those impulses. The risk of suicide and major personality changes drops markedly after 2 weeks or so. Be alert to the potential for unusual reactions, and stop the medication and check in with your physicians if you have concerns about how things are going. 1 |
| Monitor | |
| Side Effects |
| Drug Name | Stimulants: • Dextroamphetamine (Dexedrine, Dextrostat) • Methylphenidate (Ritalin, Methylin, Concerta) • Adderall |
|---|---|
| What it works on | • It is a Norepinephrine reuptake inhibitor -= it increases NE levels. It causes constriction of blood vessels and CNS effects (CNS=Central Nervous System - the brain)5 |
| Usual dose | • Dextroamphetamine SR 5 mg every morning, increase every 3-7 days by 5 mg as tolerated to 20-30 mg per day. 5 • Methylphenidate SR – start 10 mg, increase every 3-7 day by 10 mg as tolerated to 30-50 mg/da5 • Methylphenidate (Ritalin, Methylin, Concerta) 5-10 mg tid 10 |
| How to start | |
| Caveats | |
| Monitor | |
| Side Effects | • Insomnia, decreased appetite, moodiness, increased lightheadedness, agitation1 • dependency10 |
There are multiple recommendations about medications, depending on the experience of the practitioner and probably, the patient population served, whether it is primarily POTS or CFS plus POTS/OI and whether their primary patient population is adults or pediatrics.
- Dr. Roy Freeman - Center for Autonomic and Peripheral Nerve Disorders, Boston
- Dr. Blair T. Grubb - U of Toledo,Cardiology
- Dr. Peter Rowe - Johns Hopkins - Baltimore - addresses orthostatic intolerance especially in pediatric patients with CFS (Chronic Fatigue Syndrome) and hypermobility.
- Drs. Figueroa, Low, Johnson, Sandroni, Singer, Thieben - Mayo Clinic physicians-Neurology - have published primarily on management of POTS
- Dr. Julian Stewart - Vallahalla, New York
- Dr. SR Raj - Autonomic Dysfunction Center, Vanderbilt
References
- Rowe, Peter. General Information Brochure on Orthostatic Intolerance and Its Treatment. June 2010. Accessed from http://www.cfids.org/webinar/cfsinfo2010.pdf. Accessed May 28.2012.
- Rowe, Peter. Managing Orthostatic Intolerance. Webinar. September 1, 2010. Hosted by CFIDS Association of American. Accessed June 1, 2012. Written material. Slides PDF. Video.
- Figueroa JJ, Basford JR, Low PA. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med. 2010 May;77(5):298-306. Abstract. Article PDF
- Medow MS, Stewart JM, Sanyal S, Mumtaz A, Stca D and Frishman WH. Pathophysiology, Diagnosis, and Treatment of Orthostatic Hypotension and Vasovagal Syncope. Cardiology in Review 2008;16(1):4-20. Abstract.
- Freeman,Roy. Neurogenic orthostatic hypotension.NEJM 2008;358(6):615-624. Abstract
- Johnson JN, Mack KJ, Kuntz NL, Brands CK, Porter CJ and Fischer PR. Postural Orthostatic Tachycardia Syndrome: A Clinical Review. Pediatr Neuro 2010; 42:77-85. Abstract.
- Low PA and Singer W. Update on Management of Neurogenic Orthostatic Hypotension. Lancet Neurol. 2008 May; 7(5): 451–458. Abstract. Article PDF.
- Raj SR. The postural tachycardia syndrome (POTS): pathophysiology, diagnosis and management. Indian Pacing Electrophysiol J 2006;6:84–99. Abstract. Article PDF.
- Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation. 2005;111:2734–40. Abstract,
- Grubb BP. Postural tachycardia syndrome. Circulation. 2008;117:2814–2817. Abstract.Article PDF.
- Freeman, Roy. Neurogenic orthostatic hypotension.NEJM 2008;358(6):615-624. Abstract
- Grubb BP, Karabin B. Cardiology patient page. Postural tachycardia syndrome: Perspectives for patients. Circulation. 2008;118:e61–e62. Abstract. Article PDF.
- Jacob G, Costa F, Shannon JR, Robertson RM et al. The Neuropathic Postural Tachycardia Syndrome. N Engl J Med 2000;343: 1008-14.
- Chobanian AV, Volicer L, Tifft CP, et al. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. New Engl J Med.1979;301:68 –75.
- Susmano A, Volgman AS, Buckingham TA. Beneficial effects of dextro-amphetamine in the treatment of vasodepressor syncope. PACE 1993;16:1235-9.
- Grubb BP, Kosinski D, Mouhaffel A, Pothoulakis A. Use of methylphenidate in the treatment of refractory neurocardiogenic syncope. PACE 1996;19:836-40.
- Olson LG, Ambrogetti A, Sutherland DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Psychosomatics 2003;44:38-43.
- Blockmans D, Persoons P, van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med 2006;119:167.e23-167.e30.
- Gilden JL. Midodrine in neurogenic orthostatic hypotension. A new treatment.Int Angiology 1993;12:125–131.
- Jancovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind placebo-controlled study with midodrine. Am J Med 1993;95:38–48.
- Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, O'Brien PC, Slezak J, Low PA. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol. 2006 Apr; 63(4):513-8.Abstract
- Axelrod FB, Goldberg JD, Rolnitzky L, et al. Fludrocortisone in patients with familial dysautonomia—assessing effect on clinical parameters and gene expression. Clin Auton Res 2005; 15:284–291.
- Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996; 76:507–509.
- Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vsplacebo in neurogenic orthostatic hypotension: a randomized, double-blind multicenter study. JAMA 1997;277:1046-51.[Erratum, JAMA 1997; 278:388] Abstract.
Author: Kay E. Jewell, MD
Page Last Updated: August 11, 2012
