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The updated clinician must be conversant with the pharmacology of the various drugs advocated for the therapy of the balance - disorder patient and must be able to make the "right choice" with precision. The choice between anti- cholinergics, antihistaminics, phenothiazines, manoaminergics, benzodiazapines, vasodialators, etc. should be based on solid pharmacotherapeutic considerations and not made random. 
 
One of the many drugs used in the management of the balance disorder patient is the orally active histamine agonist betahist. It is advocated by some neurotologists (and promoted by pharmaceutical companies) as being specific for Meniere's diseases, which grossly limits the use of the drugs in other causes of vertigo since true Meniere's disease is a rare entity (even though the diagnosis of Meniere's debases is frequently used as a convenient dumping ground for most cases of vertigo).
Meniere's disease

Meniere's disease or Meniere's syndrome can be a disabling condition characterised by vertigo, hearing loss, tinnitus, and a feeling of fullness in the ear is occurred.The disease is caused by progressive distention of the endolymhatic space of the inner ear due to increased fluid pressure. The disease damages the hair cells in the internal ear responsible for sensing movement and balance.

It is known to be a histamine agonist for whom many clinicians do not prescribe it apprehending gastric side effects. This seriously limits the use of this drug.

—» To induce an inhibitory effect on polysynaptic neurons in the brain stem. This therapeutic action of betahist is believed to be due to its interaction with the H1 and H3 type of histamine receptors. The H3 receptors are found in the preynaptic neurons in the brain. The H3 receptors control the release of histamine and other neurotransmitter in the synapse. Histamine is believed to bind to the H3 receptors and inhibit the release of the neurotransmitters at the synapse. When betahist is administered it stops histamine from reacting with the H3 receptors and increases the release of neurotransmitter into the synapse. This inhibitory effect prevents the occurrence of massive impulses to the polysynaptic neurons and thereby brings about the antivertiginous effect. The 16mg tid dose is hence a better schedule in acute conditions than the usually advocated 8mg tid dosage.

—»To induce capillary vascodilation and enhance vascular conduction in the labyrinth, i.e., increase blood supply to the inner ear. This effect of betahist has been established by many studies viz. that of Suga & Snow (1969), Martinez (1972) and Anderson and Kubicek (1971). It has been established by Laurikainen et al. (1993) that betahist selectively increases the inner ear blood by dilation of the micro vessels in the inner ear with weak vasodilation in the other areas. Selective vasodilation of the inner ear without systematic effect is very desirable and makes the drug more user - friendly. Most other vasodialators are unselective in their action and dilate all the blood vessels in the body. This leads not only to postural hypo tension, but it also may divert the blood from the microcirculatory system of the inner ear to the larger blood vessels in the other areas and thereby actually deprive the inner ear of its necessary quota. The effects of betahist on systematic blood pressure are very minimal. This vasodilatory effect is believed to be, due to partial stimulation of the H1 histamine receptor in the inner ear blood vessels and partially due the liberation of histamine which in turn stimulates the H1 receptor of the inner ear blood vessels leading to vasdilatation and increased blood flow.

There are numerous clinically documented reports of controlled - study of betahist in peripheral vestibular disorders especially in Meniere's diseases. Though there has been a trend of reporting the role of betahist in Meniere's disease mainly, yet there are quite a few well - documented reports of betahist in non- Meniere's peripheral vestibular disorders. It has been established that distention of the endolymphatic space is the cause of Meniere's disease. It is not known with any amount of certainty what causes this distention. Of the many theories suggested as the possible cause of this endolymphatic distention, reduced vascularity of the inner ear. This however is a hypothesis and nothing has been proved yet. Moreover recent studies suggest that immunological factors and altered glycoprotein metabolism are the probable causes of this pathology. Hence there is not much rationale in advocating betahist as a drug specific for Meniere's disease. Though there is no denying of the fact that betahist increases inner ear blood flow, yet when we are not sure that reduced vascularity of the inner ear is the cause of endolymphatic distention, there is not much sense in accepting that betahist cures Menier's Diseases by increasing inner ear blood flow. Reduced inner ear blood flow is a common cause of peripheral vestibular disorders and this is definitely reversed by the increase in the inner ear blood flow caused by betahist. Hence in those cases where reduced inner ear blood flow is the cause of inner ear disturbance, betahist has a very big role. The beneficial effect of betahist in Menier's disease is probably due to its other effects, those unrelated to increased vascularity. Hence it may be concluded that betahist though not specific for Menier's, is nevertheless a very effective drug for the management of all types of peripheral vestibular disorders. It can be used in Menier's disease for exactly the same reason for which it is used in any other type of peripheral vestibular disorders.

Betahist is available as 8 mg. and 16 mg. tabs and the recommended dose is 8-16mg 3 times daily. 16mg thrice daily is the preferred dosage. The drug can be used on a long-term basis since it does not have any disturbing side effects. It does not have any sedative action like the antihistamine groups of antivertigo drugs. On the contrary, H1 agonistic effect of betahist makes the patient more alert. Betts et al (1991) objectively documented the effects of betahist, prochlorperazine, and placebo on driving ability and other factors related to impairment of awareness. The study showed that betahist did not impair driving performances and there was no impairment of awareness, whereas with prochlorperazine there was impairment of driving performance. It is apprehended by many neurotologists that betahist being a Histamine analogue will increase gastric acid secretion and cause gastritis leading to the peptic ulcer syndrome complex. This however is not true because betahist has its effects mainly on H1 and H3 receptor and not on the H2 receptor. Its affinity for H2 receptor is very very feeble. In the stomach the histamine receptors are mainly H2 receptors - upon which betahist does not have a pronounced effect. Hence gastric side effects are minimal. Nevertheless to be on the safe side it is always prudent to use betahist immediately after meals. It has been shown that betahist does not nullify the action of H2 antagonists that are used for treating peptic ulcer patients.
In conclusion it may be said that betahist in a dose of 16 mg thrice daily is a reasonably safe non- sedating antivertigo therapy, which improves the inner blood circulation. Unlike the other vestibular sedatives, betahist does not impair mental alertness. It may be used in all cases of peripheral vestibular disorders irrespective of whether it is a case of Meniere's disease or any other pathology.

"Evidence based thinking about health care"

Meniere's Disease

Meniere's Disease or Meniere's syndrome can be a disabling condition where hearing loss, tinnitus, vertigo and a feeling of fullness in the ear come together in various proportions and extents.

What causes Meniere's Disease ?

A review of over 300 articles published between 1983 and 1989 [2] covers many papers which look at the aetiology of meniere's disease. One 'theme' in the reports on aetiology and pathology seems to be an increase in immunoglobulins both in the endolymphatic fluid and in serum, occurring in a high proportion of patients with meniere's disease. It is likely to be a multifactorial condition, some sort of underlying infection (probably viral) or auto immune component seems likely in patients with this condition.
The usual clinical diagnosis is the triad of symptoms of vertigo, hearing loss and tinnitus, often with a feeling of fullness of the ear. The tinnitus and hearing loss are usually unilateral, and the disease at onset is often mild, with attacks lasting for an hour or so. In some patients, however, the onset can be much more serious, with episodes resulting in significant nausea, vomiting .
There are a number of reports concerning the incidence and prevalence of meniere's disease. The numbers quite considerably from study to study, and quite clearly different diagnostic criteria have been used at different times and in different places.
In Northern Ireland, Wilmot [3] estimated from experience over a 25 year period that the incidence was between 1 and 2 cases per 10000 population per year ( say 200 cases per million).
Stahle and colleagues [4] estimated the incidence of Meniere's disease in a Swedish population in 1973; this was possible because meniere's disease was recorded on the health records of all inpatients with the diagnosis in Sweden. A computer analysis was conducted in the Uppsaia and Skane parts of Sweden, with a combined population of over 2 million. In 1973 the two regions with a joint population of 2,263,285 had 257 patients diagnosed with meniere's disease (114 cases per million) of whom 60% were women, and most (228) cases were between 15 and 69 years.
Watanabe's [5] paper on the incidence of meniere's disease in Japan also has some interesting historical data on incidence form the UK in the 1950s and 1960s; results from Oxford in the mid 1950s suggest an incidence of about 560 per million , through higher figures are also quoted.
In the 1970s nation-wide surveys on the incidence of maniere's disease were carried out in Japan, though they reveal much of interest about age and sex distributions, severity and other aspects of disease, the only national figure for incidence based on a one-day survey was 160 cases per million, though figures on 1 week survey were much lower, at 35 per million.
In the united states, a very thorough study of the incidence and prevalence of meniere's disease carried out in population of Rochester, Minnesota, using a centralized diagnostic index at the mayo clinic. This study examined cases between 1951 and 1980 [6]. The incidence of meniere's disease in 1980 was 153 cases per million of population. Median ages of onset and diagnosis were 50 and 53 years respectively, although half the cases were diagnosed within 6 months of onset. This is most important paper giving useful information about this difficult disease. The prevalence of the disease was 2,182 per million

 
Incidence of meniere’s disease
 
Study

Incidence of meniere’s disease

Study

Year

Population

Cases per million

[3]

1979

N Ireland

200

[4]

1973

Sweden

114

[5]

1977

Japan

160 or 35

[6]

1980

United State

153

[7]

1985

Italy

82


 

A recent report from Siena [7] and Latium from two hospitals serving the needs of 104,000 people over 13 years found 111 cases, almost all being diagnosed between the ages of 10 and 70 years, with a distinct peak between 40 and 50 years. This gives an incidence of 82 cases per million. Interestingly, the incidence was some 3 times higher in hospital workers than the general population, and the authors suggested that this may reflect a higher rate of diagnosis- and that the figures for the general population may be reduced by under-diagnosis.

What is the natural history of meniere's disease?
There does not seem to be a clear answer to this question, in some patients the unilateral disease appears to "burn-out" with deafness remaining but with the vertigo and tinnitus declining . Other patients (the minority, but perhaps up to 25 % ) go on to develop a severe bilateral disorder where the vertigo remains - and where ablation of the inner ear becomes necessary.
It is suggested that food allergy or excess caffeine, nicotine or alcohol may be in some way involved in the aetiology of meniere's disease. This is far from being proven. it is suggested that avoidance of caffeine, etc. may help.
There are a number of surgical procedures [2]. Yes, there are a number, but the only RCTs that we could find reffered to betahistine. The mechanism of action of betahistine appears to be by promoting better circulation in the microvasculature, leading to reduction in endolymphatic distension.
Wilmot & Menon, 1976 [8]
This was randomized double-blind cross-over comparison of betahistine 24 mg daily and placebo for 8 or 12 weeks. Twenty-four patients began the study and analysis was performed on 22 - there were two patients with worsened symptoms who did not complete the treatments.
Patients maintained a daily symptom card for vertigo, tinnitus, deafness, fullness of ear and vomiting. Betahistine produced significantly less severe vertigo, tinnitus and fullness of ear than did placebo.



Conclusion
Meniere's disease is not common , but an average GP practice with some 6000 patients would expect to see perhaps one new case per year. A health Authority of 250,000 would see some 60 cases per year.
The disease seems to strike in middle years, most commonly between 30 and 60 years, and to affect men and women equally. The reasons for the onset and pattern of the disease are not yet understood.
There is an effective diagnostic test that should be available at all ENT clinics, and at least one effective medical treatment. Betahistine costs about Rs. 20210 a year to maintain a patient on 48 mg daily; this cost has to be set against the cost of not treating patients who, untreated, may have up to 20 attacks of long duration per month, and consume much GP and specialist clinic time

 

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