The treatment of dysautonomia can be difficult; since it is made up of many different symptoms, a combination of drug therapies is often required to manage individual symptomatic complaints. Therefore, if an autoimmune neuropathy is the case, then treatment with immunomodulatory therapies is done, or if diabetes mellitus is the cause, control of blood glucose is important. Treatment can include proton-pump inhibitors and H2 receptor antagonists used for digestive symptoms such as acid reflux.

For the treatment of genitourinary autonomic neuropathy medications may include sildenafil (a guanine monophosphate type-5 phosphodiesterase inhibitor). For the treatment of hyperhidrosis, anticholinergic agents such as trihexyphenidyl or scopolamine can be used, also intracutaneous injection of botulinum toxin type A can be used for management in some cases.

Balloon angioplasty, a procedure referred to as transvascular autonomic modulation, is specifically not approved for the treatment of autonomic dysfunction.

The opioid antagonist naloxone allowed a woman with congenital insensitivity to pain to experience it for the first time. Similar effects were observed in Na1.7 null mice treated with naloxone. As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition.

Botulinum toxin is highly effective in the treatment of hemifacial spasm. It has a success rate equal to that of surgery, but repeated injections may be required every 3 to 6 months. The injections are administered as an outpatient or office procedure. Whilst side effects occur, these are never permanent. Repeated injections over the years remain highly effective. Whilst the toxin is expensive, the cost of even prolonged courses of injections compares favourably with the cost of surgery. Patients with HFS should be offered a number of treatment options. Very mild cases or those who are reluctant to have surgery or Botulinum toxin injections can be offered medical treatment, sometimes as a temporary measure. In young and fit patients microsurgical decompression and Botulinum injections should be discussed as alternative procedures. In the majority of cases, and especially in the elderly and the unfit, Botulinum toxin injection is the treatment of first choice. Imaging procedures should be done in all unusual cases of hemifacial spasm and when surgery is contemplated. Patients with hemifacial spasm were shown to have decreased sweating after botulinum toxin injections. This was first observed in 1993 by Khalaf Bushara and David Park. This was the first demonstration of nonmuscular use of BTX-A. Bushara further showed the efficacy of botulinum toxin in treating hyperhidrosis (excessive sweating). BTX-A was later approved for the treatment of excessive underarm sweating. This is technically known as severe primary axillary hyperhidrosis – excessive underarm sweating with an unknown cause which cannot be managed by topical agents (see focal hyperhidrosis).

Mild cases of hemifacial spasm may be managed with sedation or carbamazepine (an anticonvulsant drug). Microsurgical decompression and botulinum toxin injections are the current main treatments used for hemifacial spasm.

Where an underlying neoplasm is the cause, treatment of this condition is indicated in order to reduce progression of symptoms. For cases without a known cause, treatment involves suppression of the immune system with corticosteroid treatment, intravenous immunoglobulin, immunosuppressive agents like Rituximab, Cellcept, or Imuran or plasmapheresis.

Common pharmacological treatments include:

- Mast cell stabilizers, including cromolyn sodium and natural stabilizers such as quercetin

- H1-antihistamines, such as cetirizine or ketotifen

- H2-antihistamines, such as ranitidine or famotidine

- Antileukotrienes, such as montelukast or zileuton as well as natural products (e.g., curcumin or St. John's wort extracts)

- Nonsteroidal anti-inflammatory drugs, including aspirin can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions

Fillers, binders and dyes in many medications are often the culprit in causing reactions, not necessarily the active agent, so alternative formulations and compounding pharmacies should be considered.

Lifestyle changes may also be needed. Avoidance of triggers is important. It should be emphasized that MCAS patients can potentially react to any new exposure, including food, drink, medication, microbes and smoke via inhalation, ingestion or touch.

A low histamine diet and other elimination diets can be useful in identifying foods that trigger or worsen symptoms. Many MCAS patients already have high histamine levels, so ingesting foods with high histamine or histamine liberators can worsen many symptoms such as vasodilation that causes faintness and palpitations.

There is no cure for MCAS. For most, symptoms wax and wane, but many can experience a general worsening trend over time. Lifespan for those with MCAS appears to be normal, but quality of life can range from mild discomfort to severely impaired. Some patients are impaired enough to be disabled and unable to work.

In most of the reported cases, the treatment options were very similar. Plasmapheresis alone or in combination with steroids, sometimes also with thymectomy and azathioprine, have been the most frequently used therapeutic approach in treating Morvan’s Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.

In one case, the dramatic response to high-dose oral prednisolone together with pulse methylprednisolone with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.

In another case, the subject was treated with haloperidol (6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.

In one case there high dose steroid treatment resulted in a transient improvement, but aggressive immuno-suppressive therapy with cyclophosphamide was necessary to control the disease and result in a dramatic clinical improvement.

In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propanolol, and amitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.

In another case, symptomatic improvement with plasmapheresis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.

Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvan’s Syndrome presenting itself post-thymectomy.

A number of treatments are available. The most successful non-invasive procedure is cognitive behavioural therapy (CBT), which attempts to alleviate the anxiety felt by sufferers.

In extreme cases a surgical procedure known as endoscopic transthoracic sympathicotomy (ETS) is available. Pioneered by surgeons in Sweden, this procedure has recently become increasingly controversial due to its many potential adverse effects. Patients who have undergone the procedure frequently complain of compensatory sweating and fatigue, with around 5% reconsidering getting the treatment. ETS is now normally only considered in extreme cases where other treatments have been ineffective.

The treatment options for hypohidrosis and anhidrosis is limited. Those with hypohidrosis should avoid drugs that can aggravate the condition (see medication-causes). They should limit activities that raise the core body temperature and if exercises are to be performed, they should be supervised and be performed in a cool, sheltered and well-ventilated environment. In instances where the cause is known, treatment should be directed at the primary pathology. In autoimmune diseases, such as Sjogren syndrome and systemic sclerosis, treatment of the underlying disease using immunosuppressive drugs may lead to improvement in hypohidrosis. In neurological diseases, the primary pathology is often irreversible. In these instances, prevention of further neurological damage, such as good glycaemic control in diabetes, is the cornerstone of management. In acquired generalized anhidrosis, spontaneous remission may be observed in some cases. Numerous cases have been reported to respond effectively to systemic corticosteroids. Although an optimum dose and regime has not been established, pulse methylprednisolone (up to 1000 mg ⁄ day) has been reported to have good effect.

The first treatment for Fabry's disease was approved by the US FDA on April 24, 2003. Fabrazyme (agalsidase beta, or Alpha-galactosidase) was licensed to the Genzyme Corporation. It is an enzyme replacement therapy (ERT) designed to provide the enzyme the patient is missing as a result of a genetic malfunction. The drug is expensive — in 2012, Fabrazyme's annual cost was about US$200,000 per patient, which is unaffordable to many patients around the world without enough insurance. ERT is not a cure, but can allow improved metabolism and partially prevent disease progression, as well as potentially reverse some symptoms.

The pharmaceutical company Shire manufactures agalsidase alpha (which differs in the structure of its oligosaccharide side chains) under the brand name Replagal as a treatment for Fabry's disease, and was granted marketing approval in the EU in 2001. FDA approval was applied for the United States. However, Shire withdrew their application for approval in the United States in 2012, citing that the agency will require additional clinical trials before approval.

Clinically the two products are generally perceived to be similar in effectiveness. Both are available in Europe and in many other parts of the world, but treatment costs remain very high.

Besides these drugs, a gene therapy treatment is also available from the Canadian Institutes of Health. Other treatments (oral chaperone therapy -Amicus-, plant-based ERT -Protalix-, substrate reduction therapy -Sanofi-Genzyme-, bio-better ERT -Codexis-, gene editing solution -Sangamo- are currently being researched.

Pain associated with Fabry disease may be partially alleviated by ERT in some patients, but pain management regimens may also include analgesics, anticonvulsants, and nonsteroidal anti-inflammatory drugs, though the latter are usually best avoided in renal disease.

Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of deoxyribonucleotides (dNTPs) in mitochondria.

There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. Liver transplants may benefit people with liver involvement.

Like many mitochondrial diseases, there is no cure for MERRF, no matter the means for diagnosis of the disease. The treatment is primarily symptomatic. High doses of Coenzyme Q10, B complex vitamins and L-Carnitine are the drugs that patients are treated with in order to account for the altered metabolic processed resulting in the disease. There is very little success with these treatments as therapies in hopes of improving mitochondrial function. The treatment only alleviates symptoms and these do not prevent the disease from progressing. Patients with concomitant disease, such as diabetes, deafness or cardiac disease, are treated in combination to manage symptoms.

CIP/CIM can lead to difficulty weaning a person from a mechanical ventilator, and is associated with increased length of stay in the ICU and increased mortality (death). It can lead to impaired rehabilitation. Since CIP/CIM can lead to decreased mobility (movement), it increases the risk of pneumonia, deep vein thrombosis, and pulmonary embolism.

Critically ill people that are in a coma can become completely paralyzed from CIP/CIM. Improvement usually occurs in weeks to months, as the innervation to the muscles are restored. About half of patients recover fully.

The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.

If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.

Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.

Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.

Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction.. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of NSAIDs (nonsteroidal anti-inflammatory drugs) can be used to ease painful symptoms, such as naproxen. There is limited benefit from steroids such as prednisone. Episodes of Raynaud's phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. The skin tightness may be treated systemically with methotrexate and ciclosporin. and the skin thickness treated with penicillamine.

Autonomic neuropathy (also AN or AAN) is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.

Autonomic neuropathy is one cause of malfunction of the autonomic nervous system (referred to as dysautonomia), but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy.

Scleroderma renal crisis, the occurrence of acute renal failure and malignant hypertension (very high blood pressure with evidence of organ damage) in people with scleroderma, is effectively treated with drugs from the class of the ACE inhibitors. The benefit of ACE inhibitors extends even to those who have to commence dialysis to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy.

Many health conditions can cause autonomic neuropathy. Some common causes of autonomic neuropathy include:

- Diabetes, which is the most common cause of autonomic neuropathy, can gradually cause nerve damage throughout the body.

- Injury to nerves caused by surgery or radiation to the neck.

- Treatment with certain medications, including some drugs used in cancer chemotherapy.

- Abnormal protein buildup in organs (amyloidosis), which affects the organs and the nervous system.

- Other chronic illnesses, such as Parkinson's disease, multiple sclerosis and some types of dementia.

- Autonomic neuropathy may also be caused by an abnormal attack by the immune system that occurs as a result of some cancers (paraneoplastic syndrome).

- Certain infectious diseases. Some viruses and bacteria, such as botulism, Lyme disease and HIV, can cause autonomic neuropathy.

- Inherited disorders. Certain hereditary disorders can cause autonomic neuropathy.

- Autoimmune diseases, in which the immune system attacks and damages parts of the body, including the nerves. Examples include Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. Guillain-Barre syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves.

The prognosis of dysautonomia depends on several factors; individuals with chronic, progressive, generalized dysautonomia in the setting of central nervous system degeneration such as Parkinson's disease or multiple system atrophy have a generally poorer long-term prognosis. Consequently, dysautonomia could be fatal due to pneumonia, acute respiratory failure, or sudden cardiopulmonary arrest.

Autonomic dysfunction symptoms such as orthostatic hypotension, gastroparesis, and gustatory sweating are more frequently identified in mortalities.

Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are overlapping syndromes of diffuse, symmetric, flaccid muscle weakness occurring in critically ill patients and involving all extremities and the diaphragm with relative sparing of the cranial nerves. CIP and CIM have similar symptoms and presentations and are often distinguished largely on the basis of specialized electrophysiologic testing or muscle and nerve biopsy. The causes of CIP and CIM are unknown, though they are thought to be a possible neurological manifestation of systemic inflammatory response syndrome. Corticosteroids and neuromuscular blocking agents, which are widely used in intensive care, may contribute to the development of CIP and CIM, as may elevations in blood sugar, which frequently occur in critically ill patients.

CIP was first described by Charles F. Bolton in a series of five patients.

Combined CIP and CIM was first described by Nicola Latronico in a series of 24 patients.

Due to the fact that PRS is such a severe disorder, it is almost always required to hospitalize in a child and adolescent psychiatric unit. Outpatient treatment does display symptom-free periods, but relapses of short-lived episodes of depressive symptoms or anorexia are observed. It is therefore necessary to partake in inpatient treatment. Treatment ought to involve gentle loving care. The person treating the patient must be very sensitive and tolerant because it takes a long period of time for the patient to get better, and putting pressure on them adds severity to their condition. It frequently takes several months of treatment before it is likely to employ a very steady rehabilitation programme.

Spindle transfer, where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is a potential treatment procedure that has been successfully carried out on monkeys. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using spindle transfer.

In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children.

In June 2013, the United Kingdom government agreed to develop legislation that would legalize the 'three-person IVF' procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child. The procedure could be offered from 29 October 2015 once regulations had been established.

Embryonic mitochondrial transplant and protofection have been proposed as a possible treatment for inherited mitochondrial disease, and allotopic expression of mitochondrial proteins as a radical treatment for mtDNA mutation load.

Currently, human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in Leber's hereditary optic neuropathy.