Бетасерк

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.[16][17] 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.[17]

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.[17] 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.[18] Betahistine remains unapproved by the FDA, although it is available through compounding pharmacies.[19]

Though betahistine is the most commonly prescribed drug for vertigo, there are a lot of controversies on its efficacy as well as its proclaimed mechanism of action. There are authentic studies that have shown it to be no different from a placebo in Ménière’s disease. It is often promoted as a vestibular stimulant, but scientific evidence suggests that it is a vestibular suppressant. It is also not very clear whether it is an H3-receptor antagonist as most promotional literature shows it to be, or whether it is an inverse agonist of the H3 receptors. Owing to insufficient data on its efficacy in Ménière’s disease, betahistine is not approved by the U.S. Food and Drug Administration (FDA). The much-advertised role of betahistine in augmenting histaminergic transmission and thereby inducing arousal, though beneficial is some ways in the restoration of balance after peripheral vestibulopathy, is yet not without systemic problems, and the pros and cons of histaminergic stimulation in the brain need to be assessed more by clinical studies in humans before imbibing it in clinical practice. The effect of increasing blood flow to the cochlea and the vestibular labyrinth and “rebalancing the vestibular nuclei” (as claimed in some literature) and whether they are actually beneficial to the patient with vertigo in the therapeutic doses are very controversial issues. The mechanism of action of betahistine in vertigo in general and in Ménière’s disease in particular is very confusing, and there are too many conjectural and hypothetical, if not controversial issues involved that call for close scrutiny. Everything taken together, betahistine appears to be an unduly hyped-up drug and clinicians need to review the scientific literature available and be convinced about its efficacy and mechanism of action before using it in clinical practice. This review article puts forth some controversial issues and reviews the relevant scientific literature for clinicians to analyze and then take the final call on its clinical use.

The main problem with betahistine is that reasonably authentic, large, randomized, placebo-controlled, double-blind, multicentric studies proving the efficacy are generally are not available, whereas less rigorous, observational, and low- quality studies (mostly class 3) have shown contradictory results and raised doubts on its clinical efficacy.1

 Hence, though the drug sells very well, the fact remains that most clinicians prescribe it without understanding its mode of action and are possibly influenced by the robust and aggressive marketing strategies and biased propaganda.

Hence like all other vestibular sedatives, its use should be restricted to a maximum of 3 to 5 days. Betahistine being a vestibular suppressant, by decreasing vestibular input, suppresses the vestibular system, resulting in delay in vestibular compensation.

The much-hyped histamine (H1 )–agonistic action of increasing blood flow to the brain and inner ear with betahistine is pretty weak, as this action is observed only at much higher levels than the therapeutic dose as per different studies.

Betahistine is pharmacologically approved only for Ménière’s disease by most pharmacology or medical regulatory bodies but is universally used and promoted for other causes of vertigo also, that is, as a general anti-vertigo drug.

 Most diseases presenting with vertigo, especially Ménière’s disease, have phases of waxing and waning and periods of natural remissions and cures; hence, it is impossible to gauge whether a period of remission is actually due to the drug used or due to the natural course of the disease.

 It may be having some beneficial effects in Ménière’s disease but only at very high doses that are much higher than the recommended therapeutic dosage. At commonly prescribed doses, it has been established to be no better than a placebo. It is a common experience that some patients with Ménière’s disease and even patients with other causes of vertigo do well when on betahistine, but whether it is due to betahistine or due to the natural course of the disease is debatable.