Betahistine, sold under the brand name Serc among others, is an anti-vertigo medication. It is commonly prescribed for balance disorders or to alleviate vertigosymptoms. It was first registered in Europe in 1970 for the treatment of Ménière's disease, but current evidence does not support its efficacy in treating it.[4][5]
Medical uses
Betahistine was once believed to have some positive effects in the treatment of Ménière's disease and vertigo,[3] but more recent evidence casts doubt on its efficacy.[4][5] Studies of the use of betahistine have shown a reduction in symptoms of vertigo and, to a lesser extent, tinnitus, but conclusive evidence is lacking at present.
Oral betahistine has been approved for the treatment of Ménière's disease and vestibular vertigo in more than 80 countries worldwide, and has been reportedly prescribed for more than 130 million patients. However, betahistine has not been approved for marketing in the United States for the past few decades, and there is disagreement about its efficacy.
The Cochrane Library concluded in 2001 that "Most trials suggested a reduction of vertigo with betahistine and some suggested a reduction in tinnitus but all these effects may have been caused by bias in the methods. One trial with good methods showed no effect of betahistine on tinnitus compared with placebo in 35 patients. None of the trials showed any effect of betahistine on hearing loss. No serious adverse effects were found with betahistine."
Patients taking betahistine may experience the following adverse effects:[10]
Headache
Low level of gastric adverse effects
Nausea can be an adverse effect, but patients are often already experiencing nausea owing to vertigo, so it goes largely unnoticed.
Patients taking betahistine may experience hypersensitivity and allergic reactions. In the November 2006 issue of "Drug Safety", Dr. Sabine Jeck-Thole and Dr. Wolfgang Wagner reported that betahistine may cause allergic and skin-related adverse effects. These include rashes in several areas of the body; itching and urticaria (hives); and swelling of the face, tongue, and mouth. Other hypersensitivity reactions reported include tingling, numbness, burning sensations, shortness of breath, and laboured breathing. The study authors suggested that hypersensitivity reactions may be a direct result of betahistine's role in increasing histamine concentrations throughout the body. Hypersensitivity reactions quickly subside after betahistine has been discontinued.
Digestive
Betahistine may also cause several digestive-related adverse effects. The package insert for Serc, a trade name for betahistine, states that patients may experience several gastrointestinal side effects. These may include nausea, upset stomach, vomiting, diarrhea, dry mouth, and stomach cramping. These symptoms are usually not serious and subside between doses. Patients experiencing chronic digestive problems may lower their dose to the minimum effective and may mitigate the effects by taking betahistine with meals. Additional digestive problems may require that patients consult their physician in order to find a possible suitable alternative.
Others
People taking betahistine may experience several other adverse effects ranging from mild to serious. The package insert for Serc states that patients may experience nervous-system side effects, including headache. Some nervous system events may also partly be attributable to the underlying condition, rather than the medication used to treat it. Jeck-Thole and Wagner also reported that patients may experience headache and liver problems, including increased liver enzymes and bile-flow disturbances. Any adverse effects that persist or outweigh the relief of symptoms of the original condition may warrant that the patient consult their physician to adjust or change the medication.
Betahistine has two mechanisms of action. Primarily, it is a weak agonist at histamine H1 receptors located on blood vessels in the inner ear. This gives rise to local vasodilatation and increased permeability, which helps to reverse the underlying problem of endolymphatic hydrops.
More importantly, betahistine has a powerful antagonistic effect at histamine H3 receptors, thereby increasing the amounts of the neurotransmitters histamine, acetylcholine, norepinephrine, serotonin, and GABA released from nerve endings. The increased amounts of histamine released from histaminergic nerve endings can stimulate histamine receptors. This stimulation explains the potent vasodilatory effects of betahistine in the inner ear, which are well documented.
Betahistine seems to dilate blood vessels in the inner ear, which can relieve pressure from excess fluid and act on the smooth muscle.
It is postulated that the increase in the amount of serotonin in the brainstem caused by betahistine inhibits the activity of vestibular nuclei.
Pharmacokinetics
Betahistine comes in both a tablet form and as an oral solution, and is taken orally. It is rapidly and completely absorbed. The mean plasma elimination half-life is 3 to 4 hours, and excretion is virtually complete in the urine within 24 hours. Plasma protein binding is very low. Betahistine is converted to aminoethylpyridine and hydroxyethylpyridine and excreted in the urine as pyridylacetic acid. There is some evidence that one of these metabolites, aminoethylpyridine, may be active and have effects similar to those of betahistine on ampullar receptors.[11]
Betahistine is marketed under a number of brand names, including Veserc, Serc, Hiserk, Betaserc, and Vergo.[citation needed]
Availability
Betahistine is widely used and available in over 115 countries worldwide,[7][12] including in the United Kingdom.[1]
United States
Betahistine, marketed as Serc, received initial approval from the US Food and Drug Administration (FDA) in November 1966 for the treatment of Ménière's disease. This approval was based on a single clinical study conducted by Joseph Elia and published in the Journal of the American Medical Association (JAMA) in April of that year.[13][14] However, concerns soon arose regarding the study's methodology and the strength of its findings, with public criticism appearing in publications such as the Medical Letter on Drugs and Therapeutics. This prompted an FDA investigation, culminating in the agency obtaining Elia's original study data in April 1967. Subsequent review of the data revealed inadequacies, leading the FDA to issue a notice of intent to withdraw approval in 1968.[14]
Instead of immediate withdrawal, the FDA engaged in discussions with Unimed, the manufacturer, regarding the design of a new clinical trial. This decision not to immediately remove betahistine from the market drew congressional scrutiny, particularly from Representative Lawrence Fountain, who cited the Food, Drug, and Cosmetic Act's mandate for withdrawal when substantial evidence of efficacy is lacking. Internal dissent within the FDA regarding the original approval and its reliance on a single study further complicated the situation. The controversy unfolded against the backdrop of the 1962 Kefauver–Harris Amendment, which had strengthened requirements for demonstrating drug efficacy. Ultimately, the FDA terminated betahistine's new drug application on December 21, 1972, following a lawsuit filed by Consumers Union.[14] Unimed's attempted legal challenge to maintain the drug's market presence was also unsuccessful, with the US Court of Appeals for the Second Circuit upholding the FDA's withdrawal.[15] Betahistine remains unapproved by the FDA, although it is available through compounding pharmacies.[16]
^Timmins P (2019). "Industry Update: the Latest Developments in the Field of Therapeutic delivery, 1–31 December 2018". Therapeutic Delivery. 10 (4): 215–226. doi:10.4155/tde-2019-0003. ISSN2041-5990.
^Clinical trial number NCT00829881 for "Effects of Using Betahistine to Treat Adults With Attention Deficit Hyperactivity Disorder" at ClinicalTrials.gov
^Botta L, Mira E, Valli S, Zucca G, Benvenuti C, Fossati A, et al. (June 2001). "Effects of betahistine and of its metabolites on vestibular sensory organs". Acta Otorhinolaryngologica Italica. 21 (3 Suppl 66): 24–30. PMID11677836.
^ abcCarpenter, Daniel P. (2010). Reputation and power: organizational image and pharmaceutical regulation at the FDA. Princeton: Princeton University Press. pp. 627–629. ISBN978-0-691-14179-4.
