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Use of Betahistine in Menière's disease

Menière's disease ( MD ) is an idiopathic pathological condition of the inner ear ( IE ) whose major symptoms are vertigo, fluctuating hearing loss, tinnitus, and fullness.
These symptoms are most often unilateral, although the possible bilateral involvement of the inner ear does exist.
Moreover, 75% of the patients with unilateral symptoms has also shown bilateral endolymphatic hydrops ( EH ).
Several studies have shown an extreme heterogeneity of data, with percentages of inner ear involvement ranging from 2% to 78% of the patients.

Menière's disease etiology is still under debate. Some authors believe that endolymphatic hydrops is a consequence of various factors such as genetic and environmental factors.
Others postulate that endolymphatic hydrops is the result of obstructions of the endolymph flow. Moreover, some studies support the involvement of infections and immunologic and even psychological factors.
Menière's disease is frequently associated with other diseases, such as migraine and autoimmune disease.

A US health database report has shown a prevalence of 190 per 100,000 in Menière's disease. However, in population-based studies, the prevalence fluctuates from 200 to 500 per 100,000.
Although there is a discordance in the gender-distribution of the disease, there is a general agreement that Menière's disease is a middle-age disease, and that its prevalence increases with age.

Given the high controversy for Menière's disease's etiology, treatment strategies are multiple and mostly empirical.
Moreover, given the natural instability of the disease, which includes long remission phases, clinicians have difficulties to carry out Clinical Class A studies that would provide better indications for clinical practice.

Medical treatment for Menière's disease mostly depends on the disease phase and can be divided into medications for the acute attack treatment, and prophylactic treatments prescribed during the intercritical period, between the attacks.

During the acute attacks, antiemetic and vestibular suppressant drugs, such as benzodiazepines, antihistamines, anticholinergics, and antidopaminergics, are often used to control vertigo episodes. Some of them have an additional beneficial anxiolytic effect. However, long-term administration may elicit adverse effects, such as nausea, vomiting, and impairment of vestibular compensation.
The possible autoimmune origin for Menière's disease has suggested the use of steroids, which can reduce the magnitude of the crisis and promote auditory and vestibular recovery.
Finally, osmotic diuretics ( Mannitol or Glycerol 10% ) might also be used as a treatment.

The prophylaxis treatment for the intercritical phase aims to reduce the number and severity of vertiginous crises, to relieve chronic symptoms ( instability and tinnitus ), and to prevent the progression of the disease, especially hearing loss and equilibrium disorders.
The frequency and the severity of the crises may be reduced in 2/3 of patients controlling dietary regimen, use of caffeine, alcohol and nicotine. A control of stress, fatigue, and allergy may also contribute to minimize the symptoms.
A pharmacological approach may include the use of diuretics, corticosteroids, vasodilators, or labyrinthine deafferentation with aminoglycosides.
Also complementary and alternative medicine and rehabilitation therapies are used to treat Menière's disease patients. Nevertheless, no effective therapy has shown real efficacy for long-term hearing preservation.

In Europe, the most widely used drug to treat Menière's disease patients is Betahistine ( Vertiserc ), a histamine-like molecule.
The major effect of Betahistine is in the management of vertigo.
Both preclinical and clinical studies suggest a wide range of potential effects for Betahistine. First, it modulates histaminergic neurotransmission by partially agonizing the activity of the histamine H1 receptor. Betahistine has however more potent antagonistic properties at the histamine H3 receptor, inducing an increased histamine turnover and release. Second, Betahistine has vascular effects both in the cochlea and in the brain. Third, Betahistine has effects on neuronal excitability and spike generation of neurons in the lateral and medial vestibular nuclei. It has been recently demonstrated that histamine induces an excitatory modulation by depolarizing both spontaneous firing neurons and silent neurons in the rat inferior vestibular nucleus via the histamine H1 and H2 receptors.
It is possible that the Betahistine antivertigo activity is firstly achieved by Betahistine itself and then sustained by its metabolite aminoethyl pyridine.
Finally, several studies and reviews indicate that the histamine H3 receptor plays a key role in vestibular compensation, behavioral recovery, and reduction of symptoms.

Taken together, these studies have confirmed the beneficial therapeutic effects of Betahistine in Menière's disease and vestibular vertigo patients.
However, the Betahistine improvement on the whole Menière's disease symptoms is still controversial.
The latest Cochrane review on the efficacy of Betahistine in Menière's disease concluded that Betahistine is acceptable to use; however no evidence of its efficacy has been really demonstrated.
In a meta-analysis evaluating clinical studies in patients with vertiginous symptoms, Della Pepa et al. have confirmed the therapeutic benefit of Betahistine. More recently, Nauta has also supported the therapeutic benefit of Betahistine on vertiginous symptoms in both Menière's disease and vestibular vertigo patients. ( Xagena )

Casani AP et al, Int J Otolaryngol 2018; 2018: 5359208