Amphetamines are medications that function as a central nervous system stimulant and are commonly used to treat attention deficit hyperactivity disorder (ADHD) ³. For those with dysautonomia, amphetamines have been used to help with symptoms of brain fog and fatigue ⁴. They also tighten blood vessels which can lead to an increased blood pressure ⁵. These medications can cause side effects such as anxiety, palpitations, insomnia ⁶, weight loss ⁷, headache, and dizziness ⁸, especially at higher doses. Amphetamines are considered controlled substances due to their addictive potential.

Benzodiazepines are medications that function as central nervous system depressants. They are commonly prescribed to help manage seizure disorders, muscle spasms, panic disorders, and anxiety ⁹. In individuals with multiple system atrophy (MSA), the benzodiazepine Klonopin has been used to help with sleep difficulties and improve REM sleep. It has also been used to help with palpitations in these individuals ¹⁰. These medications can cause side effects such as weakness, headache, blurred vision, vertigo, nausea, and gastrointestinal upset. Benzodiazepines are considered controlled substances due to their addictive potential.

Beta-adrenergic antagonists, also known as beta-blockers, are commonly prescribed for cardiovascular disorders and can also be used for migraine prevention and other conditions. In those with dysautonomia, beta-blockers are frequently used to help control heart rate, improve exercise capacity, and help control symptoms ¹¹ ¹². In some individuals, this medication can cause worsening of orthostatic intolerance due to lowering of blood pressure. Caution should be used in those with severe asthma ¹³. Caution should also be used in those with poorly controlled mast cell activation syndrome, as it can cause degranulation of mast cells, which can worsen symptoms ¹⁴. Beta-blockers can cause side effects such as worsening exercise intolerance, increased fatigue ¹⁵ ¹⁶, difficulty sleeping, nervousness, depression, nightmares, and gastrointestinal changes ¹⁷. If beta-blockers are stopped abruptly, rebound tachycardia can occur. To reduce this risk when stopping the medication, tapering, or slowly decreasing the dose, as indicated by the medical provider, should occur ¹⁸.

Clonidine is a centrally acting alpha2-adrenoreceptor agonist ¹⁹ that decreases the amount of norepinephrine in the body ²⁰. It can be used in those with hyperadrenergic POTS to help reduce blood pressure spikes on standing ²¹ . It can also be used to help with palpitations, tremors, orthostatic hypertension ²², and insomnia ²³. Side effects can include sedation, dry mouth ²⁴, and cognitive slowing ²⁵. Clonidine is not recommended for use in pregnant women ²⁶.

Desmopressin is an analog of antidiuretic hormone that can help the kidneys conserve water and decrease the production of urine ²⁷ ²⁸. It can help with symptoms related to orthostatic hypotension, dizziness, and fatigue ²⁹. Common side effects of desmopressin include headache, dizziness, dry mouth, and nausea ³⁰.

Droxidopa, also called Northera, is a norepinephrine precursor. It helps to increase blood pressure and decrease orthostatic intolerance ³¹. Currently, it is the only FDA-approved drug for the treatment of neurogenic orthostatic hypotension, multiple system atrophy (MSA), pure autonomic failure (PAF), and Parkinson’s Disease (PD) ³². However, it has been also studied in a small number of patients with POTS ³³. For POTS, it is used off-label ³⁴ to improve  orthostatic intolerance symptoms ³⁵. Side effects can include tachycardia, hypertension, nausea, vomiting, and headache ³⁶. In addition, Droxidopa can cause an increase in blood pressure while lying down, so the last dose should be taken at least 3 hours before going to bed ³⁷. 

Fludrocortisone is a mineralocorticoid, a weak steroid that expands the fluid volume in the blood ³⁸ ³⁹. It works by increasing sodium retention in the kidneys ⁴⁰, so the body holds onto the salt ⁴¹. Fludrocortisone is commonly used in hypovolemic POTS ⁴² when individuals experience symptoms of orthostatic intolerance, such as dizziness, syncope, and exercise intolerance ⁴³. The medication works best when taken with a high salt diet ⁴⁴ ⁴⁵. This medication can take about two weeks to reach its full effect ⁴⁶. Prolonged use of this medication can help improve blood pooling in the abdomen by improving vasoconstriction through the upregulation of norepinephrine receptors in the splanchnic bed ⁴⁷. Fludrocortisone can cause an increase in blood pressure while lying down and can also decrease potassium levels in the blood ⁴⁸. It can also lead to edema, swelling due to fluid, and osteoporosis in young women ⁴⁹. It can also cause fluid retention and may worsen migraines ⁵⁰ or headaches ⁵¹, difficulty sleeping, appetite changes, nausea, increased sweating, and nervousness ⁵². When on this medication, blood levels of electrolytes are commonly monitored ⁵³.

IVIG is composed of concentrated antibodies that help the body with fighting infections. It is commonly used in autoimmune conditions, where the body has started to attack itself, causing symptoms ⁵⁴. IVIG has been used to treat autoimmune autonomic disorders, such as autoimmune autonomic ganglionopathy ⁵⁵, autonomic neuropathy, and severe POTS with positive autoimmune markers. Research is currently being conducted on IVIG use in other forms of dysautonomia. IVIG is given as an infusion through a catheter that is inserted into a vein. The infusion can take between one to four hours and is usually given in a doctor’s office or hospital infusion center. Common side effects of IVIG can include headache, chills, fever, flushing, flu-like muscle or joint pain, fatigue, nausea, and rash ⁵⁶. In addition, IVIG can make mast cell activation syndrome symptoms worse, and individuals may need to be premedicated before infusions ⁵⁷. 

Intravenous (IV) saline infusions help to increase the fluid volume in the blood, which helps increase blood pressure ⁵⁸. Infusions are commonly used to help relieve short-term exacerbations of POTS ⁵⁹. IV saline can also help bridge the gap between initiating different therapies to provide symptomatic relief and helps improve compliance with exercise programs ⁶⁰. Routine IV saline use as a chronic treatment for POTS is not recommended due to the increased risk of infections and potential blood clots that can occur with central IV access used to sustain long-term IV therapy ⁶¹ ⁶². In rare cases, longer-term IV saline has been used in individuals with chronic POTS where symptoms are severely disabling and in individuals who have difficulty maintaining adequate oral intake of fluids or are losing fluids faster due to diarrhea or excessive vomiting ⁶³. IV saline can temporarily relieve fatigue, improve gastric motility, and headaches ⁶⁴.

Ivabradine is used to help lower heart rate without impacting blood pressure ⁶⁵ ⁶⁶. It can be used as an alternative to beta-blockers when their use is not well tolerated due to fatigue, asthma, low blood pressure ⁶⁷,  or in rare cases of allergies to beta blockers. Common side effects of ivabradine include dizziness, vertigo, nausea, headache, and fatigue ⁶⁸. Ivabradine is known to be teratogenic, meaning it is known to cause abnormal embryonic development and should not be used in pregnant women. It is recommended that adequate birth control be used when taking ivabradine ⁶⁹. Ivabradine is only FDA-approved for use in heart failure patients ⁷⁰. As such, the medication is used off-label for dysautonomia treatment and, therefore, might not be approved or covered by insurance ⁷¹. Some individuals have been able to appeal these decisions with their prescription insurance company to get the medication approved. This takes cooperation with the medical prescriber and the insurance company.

Methyldopa has a similar mechanism to Clonidine as they are both central sympatholytic medications used in patients with hyperadrenergic POTS ⁷². It is used to address orthostatic hypertension, palpitations, and tremor ⁷³.  Methyldopa has a longer half life than Clonidine, meaning that its effects remain longer ⁷⁴, and is sometimes better tolerated ⁷⁵. Methyldopa side effects include worsened fatigue, brain fog ⁷⁶, headache, muscle weakness, and upset stomach ⁷⁷.

Midodrine is a direct alpha1-adrenoceptor agonist that works by helping constrict blood vessels and increasing blood pressure ⁷⁸. This can help decrease orthostatic intolerance symptoms ⁷⁹ ⁸⁰ ⁸¹. Midodrine needs to be taken multiple times a day, usually three to four times, and should be taken during the daytime ⁸², with the first dose taken about 15-30 minutes before getting out of bed. It is recommended that the last dose be taken before 4 pm due to the increase in blood pressure that can occur, especially when lying down ⁸³. Common side effects can include urinary retention, tingling in the scalp, goosebumps ⁸⁴, and chills ⁸⁵. These side effects indicate the medication is working and should be expected ⁸⁶. The first dose can also cause a headache ⁸⁷. Individuals with prostate issues should let their doctor know as it may worsen symptoms.

Modafinil is a central nervous system stimulant used to promote wakefulness ⁸⁸. For those with dysautonomia, it can be used to help with fatigue and brain fog ⁸⁹ ⁹⁰. However, it can worsen symptoms of tachycardia ⁹¹, anxiety, and insomnia ⁹². Additional side effects can include headache, dizziness, back pain, nausea, upset stomach, insomnia, and stuffy nose ⁹³. In addition, modafinil can make certain birth control methods less effective, so talk with your medical provider if this is a concern ⁹⁴.

Somatostatins are a type of hormone produced by tissues in the nervous system and digestive systems ⁹⁵. Octreotide, an artificial somatostatin, works by helping constrict blood vessels in the gut ⁹⁶. In those with dysautonomia, it can be used in selected patients to help with symptoms of orthostatic hypotension, dizziness, fatigue, and impaired gastrointestinal motility ⁹⁷. It can cause abdominal pain, diarrhea, nausea, headache ⁹⁸, dizziness, and tiredness ⁹⁹. Octreotide should be taken on an empty stomach, at least 1 hour before a meal or two hours after ¹⁰⁰.

Pyridostigmine is a peripheral acetylcholinesterase inhibitor ¹⁰¹ ¹⁰². It works to increase parasympathetic autonomic tone ¹⁰³ and affects chemicals in the body that are responsible for communicating with nerves and muscles. Pyridostigmine can be used in those who have POTS associated with slow gastrointestinal motility, autonomic neuropathy, and non-specific muscle weakness ¹⁰⁴. When standing up, pyridostigmine can help decrease heart rate ¹⁰⁵. Diarrhea can be a common side effect and may not be well tolerated in those who already have frequent bowel movements ¹⁰⁶. Other side effects include bladder irritability ¹⁰⁷, abdominal pain and cramps, nausea ¹⁰⁸, muscle cramps ¹⁰⁹, bradycardia low heart rate, excessive sweating ¹¹⁰, and blurred vision ¹¹¹.

SSRIs are antidepressants that work to increase the level of serotonin in the brain ¹¹². They are often used to treat some of the psychological side effects of having a chronic illness ¹¹³, such as depression and anxiety ¹¹⁴. They have also helped treat hyper visceral sensitivity and irritable bowel syndrome ¹¹⁵. SSRIs' side effects can include mood changes, weight gain, difficulty falling asleep, headache, dizziness ¹¹⁶, blurred vision, dry mouth, and gastrointestinal upset ¹¹⁷. In addition, individuals taking SSRIs should be monitored for signs of suicidal ideation, as these medications can increase this feeling along with depression ¹¹⁸ ¹¹⁹. Also, be sure to let your provider know what supplements you are taking, as some supplements, like St. John's Wort, can increase your risk of serotonin syndrome ¹²⁰.

Yohimbine is an alpha-2 adrenergic blocker that works to increase blood pressure by helping increase the amount of norepinephrine, a neurotransmitter that stimulates the sympathetic nervous system to raise blood pressure ¹²¹ ¹²². This medication is commonly used in individuals with chronic autonomic failure, such as multiple system atrophy (MSA) and autonomically mediated syncope ¹²³. Side effects can include increased blood pressure, dizziness, headache, fast heartbeat ¹²⁴, tremulousness, pale skin, goosebumps, hair standing on end, increased salivation, and emotional changes ¹²⁵.