Betahistine - treatment of Meniere's syndrome

Betahistine is a tablet drug. It is used to relieve symptoms that appear against the background of malfunctions of the vestibular apparatus associated with impaired functioning of the central nervous system.

Betahistine tablets, the instructions focus on this, are used to treat Meniere's syndrome. Typically, the disease is confirmed when problems with hearing function or coordination appear. Additional signs are frequent, causeless dizziness. In the acute stage, symptoms manifest as a stroke. If left untreated, a secondary attack can be life-threatening.

The drug is also used for symptomatic treatment of vestibular dizziness - vertigo. Its causes are most often inflammatory diseases of the inner ear, as well as traumatic brain injury, intoxication and metabolic disorders.

Description of the drug

Round betahistine tablets may be white or have a slight yellowish tint. Marble effect is allowed. One tablet may contain 8 mg, 16 mg or 24 mg of the active ingredient betahistine dihydrochloride. Excipients used in the composition of the medicine are indicated in the instructions for use.

The product is an analogue of histamine and is distinguished by its ability to relieve dizziness. After administration, it is completely absorbed into the gastrointestinal tract. Its effect is aimed at improving microcirculation and permeability of the capillaries of the inner ear. After taking it, blood flow increases and endolymph pressure normalizes. As a result, malfunctions in the functioning of the vestibular apparatus are eliminated, which reduces the frequency and intensity of dizziness. Additionally, a decrease in tinnitus and an improvement in auditory perception are noted.

Taking medication

Positive results appear in the first days after starting treatment with the drug. After two weeks of use, a stable therapeutic effect is recorded. When treated with betahistine for several months, the condition of patients with Meniere's syndrome improves significantly.

Understanding what betahistine is prescribed for, you need to know how to take the tablets. The dosage is prescribed individually by the doctor, taking into account the patient’s condition. The maximum daily dose is 48 mg. Taking tablets is indicated during meals. 2-3 times a day. The recommended course duration is 2 - 3 months. Sometimes periodic treatment is carried out.

Correction during treatment is usually not required. The effectiveness of the drug decreases when combined with other antihistamines. Betahistine does not have sedative properties, so there are no restrictions regarding driving a car during treatment. It is also allowed to work on various complex mechanisms without any restrictions.

Betahistine – harmony of balance

About the article

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Regular issues of "RMZh" No. 20 dated 09/03/2009 p. 1366

Category: Neurology

Author: Ratbil O.E.

For quotation:

Ratbil O.E. Betahistine – harmony of balance. RMJ. 2009;20:1366.

The only beauty I know is health.

Heinrich Heine

Dizziness is one of the most common symptoms in medical practice. Among outpatients visiting doctors of all specialties, dizziness is the main complaint in 2–5% of cases. The cause of dizziness is an imbalance of sensory information coming from the main afferent systems that provide spatial orientation - vestibular, visual and proprioceptive. Dizziness is also one of the most common symptoms in patients with ischemic cerebral disease, especially with pathology of the vertebrobasilar system. In this group of patients, dizziness is usually caused by age-related changes in the sensory system, a decrease in the compensatory capabilities of the central mechanisms for maintaining balance, and cerebrovascular insufficiency with a predominant lesion of the vertebrobasilar system. In this case, changes in the vestibular nuclei of the trunk or vestibulo-cerebellar connections play a major role, but the so-called peripheral component, caused by atherosclerotic lesions of the vessels of the inner ear, also plays a certain role. In the clinic of neurological manifestations of cervical osteochondrosis, a special place is occupied by syndromes accompanied by severe dizziness. This is the so-called vertebrogenic vertebral artery syndrome, or posterior cervical sympathetic syndrome, which is caused by the impact of pathological bone and cartilage structures on the vertebral artery. Most often, the wall of the vessel is affected by uncovertebral growths, which deform the medial wall of the vessel or injure the surrounding sympathetic plexus, causing spasm of the artery and its branches. Manifestations of the syndrome unfold in the areas of vascularization of the branches of the vertebral artery. The clinical picture consists of headaches of occipital localization with frontal distribution, visual (in the form of subjective sensations of “fog”, “sand in the eyes”) and cochleovestibular disorders. The latter often come to the fore and are manifested by systemic and non-systemic dizziness, sometimes with nausea, vomiting, paraacusis (noise, hum, crackling) and hearing loss on the affected side. It should also be noted that there is a high incidence of dizziness (more than 20%) as a symptom in patients who have suffered uncomplicated concussions. The histaminergic system plays an important role in the functioning of the vestibular structures. Thus, the transmission of impulses from vestibular receptors and vestibular nuclei is provided primarily by histaminergic neurons. The main source of histaminergic innervation is the posterior hypothalamus, mainly the tuberomammillary nucleus, whose neurons are associated with almost all structures of the diencephalic region and telencephalon, including the basal ganglia and cortex, as well as with the brainstem and, in particular, with the vestibular nuclei complex. Histaminergic innervation is most represented in the medial vestibular nucleus. In peripheral vestibular disorders, there is an increase in spontaneous impulses of neurons of the ipsilateral vestibular nuclei, mainly the medial one. At the same time, there is a decrease in the expression of GABA receptors, which leads to the predominance of stimulating histaminergic influences. In addition, there is an increase in the density of GABA receptors in the contralateral medial vestibular nucleus. The histaminergic system also ensures the transmission of excitation between the vestibular nuclei and the vomiting center. Serotonergic, noradrenergic and dopaminergic innervation has a certain significance in the formation of connections of the vestibular system. One of the drugs that has a structural similarity to histamine and an affinity for blocking H3 receptors and stimulating H1 receptors is Tagista, containing betahistine hydrochloride. Due to the blockade of H3 receptors, Tagista increases the release of neurotransmitters from the nerve endings of the presynaptic membrane, has an inhibitory effect on the vestibular nuclei of the brain stem and improves blood supply to the inner ear. Betahistine was registered as a drug in Europe in 1970; it is a synthetic drug that has the ability to bind to H1 histamine receptors, which are located in the neuroreceptor cells of the inner ear. It has a local powerful stimulating effect, increasing the release of neurotransmitters (histamine) from the nerve endings of the receptor cells of the inner ear into the synapse. Neurotransmitters act on the precapillary sphincters, causing vasodilation of the vessels of the inner ear, increasing their permeability and thereby normalizing intralabyrinthine pressure, i.e. eliminating hydrops. In addition to affecting the receptors of the inner ear, betahistine has an effect on the receptors of the vestibular nuclei located in the medulla oblongata. Experimental work on animals has shown an increase in serotonin levels in the medulla oblongata. This leads to a decrease in the activity of the vestibular nuclei, a decrease in their excitability and the cessation of dizziness. Thus, a vestibulodepressive effect is manifested. The effectiveness of Tagista is associated with a decrease in both spontaneous and evoked impulses from vestibular receptors and vestibular nuclei. It was shown that the administration of betahistine led to a dose-dependent decrease in the frequency of spontaneous impulses from semicircular tubule receptors. In addition, Tagista helps to reduce the intensity and amplitude of impulses of neurons of the lateral vestibular nucleus both at rest and during stimulation. Tagista also stimulates the synthesis of endogenous histamine, as evidenced, in particular, by the increased synthesis of messenger RNA encoding histidine decarboxylase, the main enzyme in histamine synthesis. Along with the effect on histamine receptors in the peripheral and central vestibular structures, Tagista has a vasoactive effect. The drug causes dilation of the arterioles and capillaries of the inner ear, which leads to a selective increase in blood flow. In addition, taking the drug contributes to a slight increase in cerebral blood flow both in the vertebrobasilar and carotid areas, which leads to an improvement in cognitive functions in patients with chronic cerebrovascular insufficiency (Table 1). The administration of betahistine reduces the frequency, severity and duration of attacks of systemic dizziness (Table 2). Along with the positive effect on vestibular function, there is also an improvement in hearing during treatment, which is apparently due to the vasoactive effect of the drug. During a study of the effectiveness of betahistine [A.B. Gekht, 2001] in elderly patients with chronic vertebrobasilar insufficiency, significant positive dynamics of cochleovestibular disorders proper (dizziness, hearing loss, ataxia) were revealed. There was also a decrease in headaches and visual field defects. High tolerability of betahistine is very important when used in elderly patients with concomitant somatic pathology. Betahistine is also effective for relieving attacks of acute dizziness (vertigo). The drug reduces the frequency, duration and severity of attacks. Until recently, the medical trend has been to control very severe attacks of vertigo with labyrinthine drugs (prochlorperazine). Sedation, or drowsiness, is a common side effect of these drugs, which delay vestibular compensation [Kirtane, 1999]. Tagista at a dose of 16 mg 3 times a day. – best choice for controlling acute dizziness. In the clinic of acute vertigo, which occurs largely due to imbalances in electrical potentials in the vestibular nuclei of both hemispheres, the following tendency is revealed: during the acute phase, cerebellar cells inhibit the vestibular nuclei and thereby alleviate symptoms. This phenomenon is very figuratively called “cerebellar clamp”. Gradually, over several weeks, the vestibular nuclei of the undamaged side take over the function of the affected nuclei. This is observed anatomically as the emergence of cross-synapses and leads to a balance in the impulse activity of the nuclei of both sides. Once this happens, the vestibular nuclei are gradually released from the “cerebellar clamp” effect. This whole process is called “compensation”, thanks to which a person or animal who has suffered from acute attacks of vertigo regains a sense of balance, even if the original pathology is irreversible (Fig. 1-3). Most medications for dizziness cause sedation and CNS depression. This slows down the compensation process, which is so necessary for the patient's rehabilitation. Betahistine, which does not cause CNS depression, does not interfere with the compensation process. Tagista is not a sedative and therefore does not interfere with the patients’ normal lifestyle. The drug really has an “acceleration” effect on vestibular adaptation, which is vital for the speedy rehabilitation of patients with acute peripheral vestibular catastrophe. Biswas (1998), Tighilet et al. (1995) concluded from observations that taking betahistine per os (50 or 100 mg/per 1 kg of body weight) significantly accelerates recovery, restores statics and dynamics after transection of the left vestibular nerve in experimental cats and thus significantly accelerates vestibular compensation. Tagista is available in tablets of 8, 16 and 24 mg. The optimal daily dose is 48 mg. The most adequate therapeutic effect is achieved when taking the drug with food. The drug should be used with caution in patients suffering from peptic ulcer of the gastrointestinal tract (including a history of it), pheochromocytoma, and bronchial asthma. These patients should be monitored regularly during treatment. The duration of treatment in all cases is determined by the attending doctor, taking into account the clinical picture and individual characteristics of the patient.

Literature 1. Vereshchagin N.V. Pathology of the vertebrobasilar system and cerebrovascular accidents. M: Medicine, 1980. 312 p. 2. Vilensky V.S. Complications of stroke: prevention and treatment. St. Petersburg: Foliant, 2000. 128 p. 3. Gekht A.B., Gusev E.I., Bogolepova A.N., Alferova V.V. Principles of rehabilitation and pharmacotherapy of stroke patients in the recovery period // Materials of the VIII All-Russian Congress of Neurologists. Kazan, 2001. P. 220. 4. Gorbacheva F.E., Natyazhkina G.M., Chuchin M.Yu. Dizziness // Dizziness. – Consilium medicum. – 2001.– Appendix – pp. 63–66. 5. Gusev E.I., Gekht A.B., Bogolepova A.N., Dorzhieva N.N., Shimrigk G., Haas A. Results of a 3-year follow-up observation of patients with ischemic stroke (based on materials from the Stroke Data Bank ) // Neurological Journal, 2002. 6. Gusev E.I., Nikonov A.A., Skvortsova V.I. and others. Treatment of dizziness with Betaserc in patients with vascular and traumatic brain lesions // Journal. neurol. and a psychiatrist. 1998. No. 11. 7. Isaikin A.I., Yakhno N.N. Vertebral-basilar insufficiency // Breast cancer. 2002.Vol. 9, No. 25. 8. Lavrov A.Yu. Application of Betaserc in neurological practice // Neurological journal No. 2, 2002, vol. 6. 9. Abdulkerimov Kh.T., Markov I.S., Usachev V.I. Efficacy of Betaserc for vestibular disorders // Journal. neurol. and psychiatrist. 2002; 6: 50–52. 10. Boyko A.N., Derevyanko S.N., Luchikhin L.A., Slanova A.V., Gusev E.I. Betaserc in the symptomatic treatment of multiple sclerosis // Journal. neurol. and psychiatrist. 2002; 1:42–45. 11. Golubev V.L. Dizziness // Treatment of nervous diseases 2003; 2:3–9. 12. Kadymova M.I., Polyakova T.S. Application of Betaserc in patients with cochleovestibular disorders // Otorhinolary Bulletin. 1998; 3:7–9. 13. Lacour M. Histamine Vestibular function and vestibular compensation. Amsterdam: Elsvier 1998; 11–16. 14. Timmerman H. Pharmacotherapy of vertigo: any news to be expected? Acta otolaryngol 1994; Suppl 513:28–32. 15. Decher H. Horstorungen bel vertebrobasilar insuffizienz // Laryngol. Rhinol. Otol. – 1975. – Bd. 54, N9. – S. 728–734. 16. Oas JG, Baloh RW Vertigo and the anterior inferior cerebellar artery syndrome // Neurology. – 1992. – Vol. 42, N12. – P. 2274–2279. 17. Rivega V. M., Meyer JS, Baer PE at al. Vertebrobasilar arterial insufficiency with dementia: controlled trials of tritment with betahistine dihydrochloride. J Am Geriatr Soc 1974; 22: 397–406. 18. Babiyak V.I., Lantsov A.A., Bazarov V.G. Clinical vestibulology: A guide for doctors. – St. Petersburg: Hippocrates, 1996. – 336 p. 19. Oosterveld WJ Vertigo–Current concepts in managament 1985; 30: 275–283. 20. Braidu RA, Cute DG, Mhapanka JB, Narurka NK, Patil SF. Control symptoms of acute vertigo with betahistine. RMJ vol. 16, Pain syndrome, 2008, p. 45–51.

Contraindications

Absolute contraindications are hypersensitivity to the active substance and other components of the product. Treatment with the drug is not prescribed until adulthood. The drug is contraindicated during pregnancy and lactation, since there is no data on its effect on the fetus and newborn child. Betahistine should not be used if you are lactose intolerant. Caution should be exercised when prescribing medication when the following diseases are diagnosed:

• Peptic ulcer of the stomach or duodenum.
• Pheochromocytoma.
• Bronchial asthma.

It is not recommended to use betahistine, the instructions for use indicate this, in combination with antihistamines. In addition, it is recommended to refuse the product if:

• Hives.
• Arterial hypotension.
• Allergic rhinitis.

Since studies on the reaction to the drug in renal and hepatic failure have not been conducted, it is recommended to refuse treatment for these pathologies.

Betahistine dihydrochloride

Betahistine dihydrochloride (Betaserc®) in the treatment of dizziness

The first drug that proved effective in treating dizziness was histamine. Its intravenous administration eliminated dizziness in patients with the disease

Meniere. Action of histamine in the body:

• exciting;
• energy conversion (glycogen hydrolysis);
• controls behavior (locomotor function, eating, drinking, sexual function);
• neuroendocrine (increases the synthesis of adrenocorticotropic hormone);
• autonomic (blood pressure).

Histamine is a neurotransmitter and a locally acting hormone. However, its role in the body has not been fully studied. Three types of histamine receptors have been discovered: H1, H2 and H3. They are located with varying densities in almost all parts of the brain.

H1-postsynaptic receptors. Excited by histamine. Their excitation leads to dilation of capillary vessels, spasm of the smooth muscles of the gastrointestinal tract and bronchi, and an increase in the production of mucus in the respiratory tract. Blocked by classic antihistamines. The role of these receptors in the central nervous system has not been fully studied.

H2 - postsynaptic receptors. Found in the heart, gastrointestinal tract (stomach), uterus and central nervous system. Excitation of these receptors increases the secretion of gastric juice and mucus in the respiratory tract and stimulates the activity of the heart. Blocked by cimetidine. Their role in the brain has not been studied.

H3 - presynaptic. They are located in the cerebral cortex, although histaminergic neurons are not found there. Their role is also subject to clarification. The physiological effect of activation of these receptors is a decrease in histamine synthesis and release.

Receptors H1, H2, H3 are found in almost all areas of the brain, but with different densities. A high density of histaminergic neurons is noted in the region of the stria vascularis in the inner ear and the tuberomammillary nuclei of the posterior hypothalamus. Their efferent fibers are found throughout the brain.

However, histamine caused a significant number of side effects, such as severe headache, facial flushing, diplopia and vomiting. Therefore, the drug Betaserc® was developed, which is an analogue of histamine, but without its disadvantages. Chemically, betahistine is 2.2methylaminoethylpyridine dihydrochloride. Unlike histamine, it can be taken orally. The drug has a favorable pharmacokinetic profile - it is quickly and completely absorbed from the tablet form, the average half-life in plasma is 3-4 hours, and is almost completely excreted in the urine within 24 hours. Plasma protein binding is very low.

Betaserc® has a pharmacological effect similar to histamine. According to modern concepts, betahistine dihydrochloride has three levels of action:

1. On the cochlear blood flow.
2. To the central vestibular apparatus.
3. To the peripheral vestibular apparatus.

Specific effect of betahistine on cochlear blood flow: The stimulating effect of betahistine on the H1 receptors of the blood vessels of the inner ear leads to local vasodilation and increased vascular permeability, which helps eliminate the causes of endolymphatic hydrops. It is believed that betahistine's relatively weak affinity for H1 receptors does not fully explain its clinical effectiveness.

Experimental studies have shown that betahistine has a vasodilating effect in the brain and periphery and improves microcirculation in the auditory system, cochlea and vestibular apparatus. The effect depends on the dose and is manifested to a greater extent in the vascular network of the cochlea. It is possible that this effect is mediated by presynaptic adrenergic neurons.

In patients with cerebrovascular diseases, under the influence of the drug Betaserc®, regional cerebral blood flow increases, and in elderly patients mental function improves.

Effect of Betaserc® on the central vestibular apparatus: Betahistine is a weak agonist of H1 receptors and a rather powerful antagonist of presynaptic H3 receptors, which regulate the release of histamine and some other neurotransmitters. Dr. Lacour M/ (1998) found that betahistine clearly accelerates the recovery process in cats after unilateral vestibular nerve neurectomy. Neurochemical studies have revealed a marked and sustained decrease in the amount of histamine in the vestibular and tuberomammillary nuclei after neurectomy. This reduction was significantly greater in cats that received betahistine. That. with vestibular disorders, the release of histamine increases, which helps restore vestibular function. Betahistine accelerates the recovery process by promoting even greater release of histamine, which is explained by its properties as an H3 receptor antagonist. Research by Dr. Dutia M. (1995) showed that immediately after unilateral labyrinthectomy there is a significant increase in the excitability of cells in the medial vestibular nucleus under the influence of histamine.

It is currently believed that betahistine relieves dizziness by being an H1 receptor agonist and an H3 receptor antagonist, and its effect on cerebral blood flow is due to the fact that it acts as an H1 receptor agonist. Drugs that are H3 receptor antagonists are of particular value for the treatment of patients suffering from dizziness, since they do not cause sedation and drowsiness, and therefore do not disrupt the processes of central compensation of vestibular function. Receptor studies have shown that Betaserc® has a very strong affinity for histamine H3 receptors and a weak affinity for histamine H1 receptors. Affinity for H2 receptors is practically absent. By blocking H3 receptors, betahistine increases the release of neurotransmitters from nerve endings. An increased amount of histamine can stimulate H3 receptors, thereby potentiating the direct agonistic effect of Betaserc® on these same receptors. This explains the reason for the powerful vasodilating effect of Betaserc® in the inner ear. Betaserc® reduces the electrical activity of the vestibular nuclei in the brain stem, which is due to an increase in a number of neurotransmitters (including serotonin), the release of which is mediated by H3 receptors. Interaction with H3 receptors may be the main mechanism by which betahistine dihydrochloride exerts its clinical effects.

Thus, we can conclude that the effect of Betaserc® as a whole is undoubtedly more complex than originally thought, apparently including:

1. Inhibitory effects on the vestibular nuclei, which are realized directly through H3 receptors.
2. Vasodilation in the inner ear, which is realized indirectly through H3 and H1 receptors.
3. Inhibitory effects on the impulse activity of ampullary receptors.

That. through a direct agonistic effect on the H1 receptors of the vessels of the inner ear, as well as indirectly through an effect on the H3 receptors, it improves microcirculation and capillary permeability, normalizes endolymph pressure in the labyrinth and cochlea, and increases blood flow in the basilar arteries. Betaserc® also has a pronounced central effect, being an inhibitor of H3 receptors in the nuclei of the vestibular nerve, and also normalizes neuronal transmission in polysynaptic neurons of the vestibular nuclei at the level of the brain stem. In recent years, it has also been revealed that Betaserc® indirectly, when acting on H3 receptors, increases in the brain stem the level of a neurotransmitter such as serotonin, which reduces the activity of the vestibular nuclei.

Betaserc® has been studied in many clinical studies, including clinical instrumental studies, as well as controlled clinical trials in comparison with placebo and other drugs. These studies showed that Betaserc® is effective when taken orally and very rarely causes side effects. In addition to dizziness, the drug is also effective for relieving noise and ringing in the ears. The use of the drug in the treatment of Meniere's disease in the early stages can stop hearing loss by reducing the frequency of attacks, hence damage to sensory auditory cells.

Numerous studies have demonstrated the preventive and therapeutic effect of Betaserc® in relieving dizziness. The preventive effect of the drug is expressed in a significant reduction in the frequency of vertigo attacks, due to changes in blood flow in the brain or labyrinth. This is especially important in Meniere's disease and recurrent dizziness. Betaserc® significantly reduces the duration of nystagmus. Research by E.I. Gusev and co-authors has established that Betaserc® is effective both for relieving attacks of dizziness and for preventing relapses.

The effectiveness of Betaserc® in various diseases and pathological conditions accompanied by dizziness has been shown in many randomized, double-blind, placebo-controlled studies that meet the requirements of evidence-based medicine.

Betaserc® does not have a sedative effect even when used in high doses, therefore it promotes the development of vestibular adaptation. Therefore, unlike other drugs, it can be successfully used in combination with vestibular adaptation training.

Side effects: Clinical studies have shown that Betaserc® is very well tolerated. In most clinical trials there was no mention of side effects that occurred.

1. Lack of sedation and drowsiness. The drug stimulates H1 receptors rather than blocks them, so patients taking Betaserc® remain active and continue to lead a normal lifestyle.
2. The ability to drive a car is not impaired.
3. Low level of stomach side effects. Betaserc® does not increase gastric acid secretion in humans. However, it should be used with caution in patients with peptic ulcers.
4. Lack of antidopaminergic effects. Betaserc®, as a rule, does not cause extrapyramidal side effects, unlike, for example, prochlorperezine, which often causes parkinsonism.

Thus, Betaserc® is a safe and well-tolerated drug, and the only contraindications to its use are hypersensitivity to the drug and pheochromocytoma. It is not recommended to prescribe the drug during pregnancy and lactation. The drug should be prescribed with caution to patients with peptic ulcer disease and bronchial asthma.

Dosage. Numerous pharmacological studies have shown that the optimal daily dose of Betaserc® is 48 mg. The drug was equally effective when taken twice a day (2 x 24 mg) and three times a day (3 x 16 mg) for the same daily dose. Both regimens were well tolerated.

(Publications from Solvay Pharma were used in preparing this article)