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Sunday, January 25, 2009



Very few of the medications listed below have been tested in formal clinical trials in those with CFS. Some drugs have been tested in clinical trials in those who faint but are otherwise healthy. Some drugs are typically given in combination with others (for example, Florinef), but rigorous studies of combination therapy have not yet been done. The information presented is based on the available research, and the clinical experience of our group and others who study orthostatic intolerance.


Brand name: Florinef

Type of drug: a mineralocorticoid steroid

Indication: NMH or POTS

Action: Florinef acts in the kidney to help the kidney retain sodium that would otherwise be lost in the urine, and it may also help blood vessels constrict more readily in response to epinephrine and norepinephrine. It helps the body avidly retain the salt you eat. It does so at the expense of losing potassium into the urine, so it is important to take in adequate amounts of potassium each day (a list of foods high in potassium is appended). We recommend potassium supplements when people start on Florinef, regardless of the serum potassium level, and especially if individuals remain on the drug for several months. A sustained release potassium preparation (containing 8-20 mEq) given once daily has been well tolerated by our patients.

In our clinical trial of Florinef in adult chronic fatigue syndrome patients with NMH, the drug was not effective when given by itself. Several studies suggest the drug is helpful in treating NMH and POTS when given in combination with an increased intake of salt and other medications (for example, with a low dose of a beta blocker), but no rigorous studies of combination therapy have been conducted, and no studies in adolescents have been performed.

Common confusions: Cortisone and fludrocortisone differ. Florinef has none of the anti-inflammatory properties of cortisone or prednisone, and it has no effect on blood sugar as cortisone does. Florinef is not a muscle building (anabolic) steroid. NMH or POTS patients taking Florinef should be on a high salt diet.

Common side effects: To reduce the chance of Florinef causing an elevated blood sodium level, make sure to drink lots of fluids while taking Florinef. 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. Depression occurs in fewer than 1 in 20 patients, but patients need to be aware of this when they start on the drug, and to know to stop Florinef if such depressed mood occurs. Some have found that minor side effects will disappear after a couple of weeks, and it is worth persevering with the medication provided that the side effects are minor. Some develop worse acne on Florinef. The tablet has a tiny amount of lactose in it, and may cause discomfort to those who are extremely allergic to milk protein. Special pharmacies can compound the drug without lactose or milk protein (e.g, Abrams Royal Pharmacy, 8220 Abrams Rd., Dallas, TX 75231; Tel: 214-349-8000; Fax: 214-341-7966).

With high doses, or even low doses over a long period of time, Florinef can lead to an elevation of blood pressure (BP), especially when other medications like oral contraceptives are added to the regimen. For this reason, we recommend that BP be monitored carefully, especially in the weeks after starting on the drug, and monthly once a stable dose is achieved.

Suggested doses for patients with NMH or POTS: 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 1/4 tablet per day (0.025 mg). If the 1/4 tablet dose is tolerated for 4-7 days, increase to ½ tablet for 4-7 days, then to 3/4 tablet or a full 0.1 mg tablet. By stepping up the dose gradually, you can better determine the right dose (some patients may only need ½ tablet or ¾ tablet). Some patients report that splitting the dose (half in the morning and half with the evening meal) provides a more even effect, but occasionally people have to return to a once a day morning dose because the Florinef taken later in the day causes them to develop insomnia.

Each patient's tolerance of the drug, and response to it is somewhat different, so we recommend regular visits while the doses are being adjusted. If there is no improvement, or more bothersome side effects appear (worse headaches, substantial weight gain, and certainly depressed mood) we recommend stopping the medication. If people continue to experience some benefit from week to week at a particular dose, it makes sense to continue on that dose. If there are no adverse effects on a dose of 0.1 mg per day, but no impressive therapeutic benefits have occurred after about a month, we will try increases to a maximum of 0.15 or 0.2 mg (1 ½ - 2 tablets) per day. Whether further increases would be beneficial is unclear. If unsure about whether the drug is having a beneficial effect, it can be stopped for a few days to see if symptoms worsen. When Florinef is helping, but only incompletely, we usually continue this medication and then add other classes of medication to it.

Comments: It is important to be sure that you are taking an adequate amount of fluid. We recommend checking the serum electrolytes periodically, but the optimal frequency for doing so is not established. Because licorice root can have the same effect on blood pressure as Florinef, combining these two medications should be avoided. If BP increases over time, a reduction in the Florinef dose may be indicated.

Use in pregnancy: consult with your health care provider.


Brand names: Tenormin (other similar medications like propranolol or metoprolol may be as effective, but the greatest experience has been with atenolol, and we will focus on atenolol here).

Type of drug: a beta-blocker

Indications: NMH and POTS

Action: Atenolol blocks the effects of adrenaline (epinephrine), and acts both to decrease the heart rate and to prevent the forceful heart contractions that may help trigger NMH.

Common side effects: Some individuals complain of headaches or fatigue after atenolol, and others have worse lightheadedness or worse symptoms in general. If these problems arise, we usually stop the medication. Like other beta-blocker drugs, atenolol can lead to constriction of the airways in individuals with a history of asthma. If cough or wheezing develop soon after starting the drug, it may need to be stopped. For those with mild asthma, our impression has been that an inhaled steroid (eg, Pulmicort, Flovent) may allow patients to tolerate the beta-blocker without increased airway reactivity. Atenolol can also cause emotional depression. Atenolol is less likely than other beta-blocker drugs (such as propranolol [Inderal]) to lead to nightmares, confusion, and hallucinations. Atenolol and other beta-blocker drugs can interfere with the body's ability to correct low blood sugar, so the drug must be used with extreme caution (if at all) in diabetics. The activity of the drug can be decreased when it is used in conjunction with non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin).

Doses: The usual starting dose of atenolol for older adolescents and adults is 12.5-25 mg per day, but doses of up to 100 mg per day are used. For those with NMH, we usually aim for 1 mg of atenolol for every kg of body weight. For example, an individual weighing 62 kg (136 lb) would likely do well with between 50 and 75 mg of medication per day. People are unlikely to tolerate higher doses if their resting heart rate is below 50 beats per minute. The ideal dose for those with POTS is not well defined, and some authorities believe that lower doses may be preferable. Further study is needed to determine whether patients would do better with one form of beta blocker (selective beta blocker like atenolol) versus another (non-selective beta-blocker like propranolol).

Use in pregnancy: consult with your health care provider.


Brand names: Ritalin, Dexedrine, Adderall, and others. No studies have compared the relative efficacy of one to the others for those with NMH or POTS.

Indications: NMH or POTS

Action: The stimulant medications available for the treatment of attention deficit disorder are effective as vasoconstrictor drugs for the treatment of NMH and POTS. By improving constriction of blood vessels in the peripheral circulation, they improve the amount of blood flow returning to the heart. These medications may also exert their beneficial effects through actions on the central nervous system as well.

Doses: The maximum dose depends on the individual's weight. We begin with low doses, increasing once it is clear the patient tolerates the drug.

Dextroamphetamine: Dexedrine spansules are the sustained release form of the medication, and because they contain no milk protein they are the ones we use first for patients with milk allergy. The average starting dose for adolescents and adults is one 5 mg Dexedrine spansule each morning for 3 days or so. If there is no apparent improvement at this dose by that time, we increase the dose to two of the 5 mg spansules in the morning (at the same time). After another 3-4 days, if there is no improvement, increase to 3 spansules (15 mg) in the morning. The top dose is different for each person, and further increases may be needed.

Methylphenidate: the dose of methylphenidate depends on the individual's weight, but we usually try to keep the dose below approximately 0.5 mg per kg of body weight. We begin with low doses, increasing once it is clear the patient tolerates the drug. The starting dose for school-age children as well as adolescents and adults is 5 mg, given first thing in the morning, repeated if necessary 4 hours later. Unless the 5 mg once or twice daily is enough to control symptoms, we recommend increasing the dose to one of the following:

10 mg in the AM and 4 hours later
10 mg in the AM, 5 mg four hours later
10 mg in the AM, 5 mg four hours later, and 5 mg four hours after the 2nd dose

The maximum dose can be substantially higher, up to about 1 mg of drug for every kg of body weight, but a dose of as little as 5 mg per day may be all that is required. One adolescent, for example, had her best response on a regimen of 15 mg per dose given three times a day.

Expected therapeutic effects: The short-acting forms of methylphenidate or dextroamphetamine usually start to take effect after 30-45 minutes or so, and the duration of effect is usually 4 hours or so. If the stimulant medications are working at a particular dose, we expect individuals to feel less lightheadedness, headache, or fatigue. There may also be improvement in the ability to concentrate and stay on task. Individuals usually know soon after taking the first few doses if the drug is having a beneficial effect at that dose. The stimulants are controlled substances, so the prescriptions have to be written more frequently, and physicians cannot ask for refills on the same prescription.

Side effects: The main side effects of the stimulants are insomnia, a reduction in appetite, moodiness, and occasionally abdominal pain. Some patients describe increased lightheadedness, agitation, and other bothersome symptoms. If these develop, we usually stop the drug and move on to other medication trials.

Comment: We have found these medications to be particularly helpful for those who had a history of hyperactivity or attention deficit disorder in childhood, or a family member with the disorder, either alone or in combination with other NMH treatments.

Use in pregnancy: consult with your health care provider.


Brand name: ProAmatine

Type of drug: Midodrine is classified as an alpha-1 agonist, or vasoconstrictor drug. Unlike the stimulant drugs, it is not thought to have direct central nervous system effects.

Action: The main effects of midodrine are to cause blood vessels to tighten, thereby reducing the amount of blood that pools in the abdomen and legs, shifting that blood volume into the central circulation where we want it to be. The drug has been used in thousands of individuals around the world, and appears to be well tolerated.

Side effects: The main side effects from midodrine in those with orthostatic hypotension (a condition similar to, but not the same as, neurally mediated hypotension) 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%.

Common side effects to be expected include a sense of the 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. Adolescents and young adults with NMH and POTS should not be at risk for the same degree of high blood pressure as those with orthostatic hypotension (whose average age is closer to 50-60 years), but one needs to watch for this.

Dose: A conservative starting dose for midodrine is 2.5 mg three times daily to ensure that the dose is tolerated. A reasonable dose progression follows:

2.5 mg three times a day for 1-2 days (Each dose taken approximately 4 hours apart).
5.0 mg three times a day for 1-2 days
7.5 mg three times a day for 1-2 days
10.0 mg three times a day

If there is substantial improvement at a lower dose, then it may be wise to stay at this dose for a longer period. It is not always necessary to march up to the 10 mg three times a day dose. The drug effect lasts only about 3-4 hours, so the medication may need to be spaced differently once it is clear that it is having a beneficial effect.

Use in pregnancy: consult with your health care provider.


The selective serotonin re-uptake inhibitor (SSRI) medications most commonly used for those with NMH or POTS are Paxil, Zoloft, and Prozac, but others in this class of antidepressant medications are likely to work as well. The doses used to treat NMH or POTS are similar to those used for the treatment of depression; 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). 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. Some patients describe worse orthostatic intolerance or fatigue on the SSRIs. In patients with increased anxiety or depressed mood, these medications may be particularly helpful, but one does not need to have either anxiety or depression for the SSRIs to help with NMH or POTS.

Use in pregnancy: Several studies suggest they are safe, but consult with your health care provider.


Brand name: Norpace

Type of drug: an anti-arrhythmic, anti-cholinergic drug

Indication: NMH (no studies in POTS)

Action: Norpace blocks the response to adrenaline (epinephrine), and prevents the forceful heart contractions that occur in neurally mediated hypotension.

Side effects: Some individuals complain of headaches or fatigue after Norpace, and others have worse lightheadedness. Other possible side effects are dry mouth, constipation, blurred vision, and impaired urination. This drug can activate glaucoma in some individuals. Norpace should not be taken with erythromycin, clarithromycin, azithromycin, phenothiazines, trimethoprim-sulfamethoxazole, cisapride, or other Class 1a anti-arrhythmic agents because of the potential for triggering serious heart rhythm abnormalities. For similar reasons, it should be used with great caution in those on tricyclic antidepressants. Due to its ability to reduce the forcefulness of the heart's pumping action and to trigger arryhthmias, its use should be considered very carefully in those with heart disease. Use of the drug by those already taking beta-blockers or calcium channel blockers requires similar caution.

Doses: typically the dose for older adolescents and adults is 100-200 mg of the CR (sustained release) preparation twice daily, although higher doses are sometimes tolerated, and lower doses are sometimes effective. It is preferable to take it on an empty stomach, an hour before or two hours after eating, but it can be taken with food to reduce stomach irritation. Some individuals with medication sensitivities need to have the drug started at 100 mg each morning for a week, with increases of 50 or 100 mg per week (using the 150 mg CR capsule).

Use in pregnancy: Consult with your health care provider.


Clonidine is a medication first introduced for control of high blood pressure, but it can also improve blood volume in a subset of those with orthostatic intolerance. It works in part by reducing sympathetic nervous system outflow from the brain.

It is also used as a drug for those with attention deficit disorder, and has been reported to help reduce anxiety, reduce withdrawal symptoms in those who are on narcotic medications, and improve sleep. There is also some evidence that it can improve stomach emptying in patients with delayed gastric motility. We have found that a proportion of patients with CFS benefit from it.

The starting dose is ½ a tablet (0.05 mg) at night for 3-7 days, then increasing to a full 0.1 mg tablet at night. Higher doses are sometimes tolerated. Side effects can include worse fatigue and lightheadedness (due to its ability to lower blood pressure), and dry mouth. If side effects are mild in the first week, we usually ask patients to continue on the drug to see if these effects resolve and the therapeutic benefit becomes evident over the next few weeks. If side effects are more impressive, we suggest stopping the medication.

If people have been taking clonidine for a prolonged period of time, they need to wean off it slowly to avoid developing rebound hypertension.

For those who are allergic to milk protein the Mylan brand form is lactose free.

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