Vertigo Management – Mapping prevalence and treatment. Understanding once a day preparation usage and place in therapy.
INTRODUCTION TO SUBJECT
Dizziness accounts for an estimated 5 percent of primary care clinic visits. The patient history can generally classify dizziness into one of four categories: vertigo, disequilibrium, presyncope, or light-headedness. The main causes of vertigo are benign paroxysmal positional vertigo, Meniere’s disease, vestibular neuritis, and labyrinthitis.
More than two million people per year visit their doctor for vestibular / balance disorders. These disorders are the ninth most common complaint that leads patients to visit their family physicians. Furthermore, it is one of the most common reasons elderly people seek medical advice. Patients often describe balance problems in terms of vertigo, dizziness, imbalance, blackouts, light-headedness, and motion sickness. But, not all of these symptoms are always caused by disorders of the vestibular system. Moreover, although one person may describe a balance problem using one or more of these terms, another person may use a different combination of these terms to describe the very same condition. In fact, some people will even use the word dizziness to indicate that they simply do not feel well. It is hence quite a task for the clinician to decipher the patient’s complaints and put them in their proper perspective. A very thorough history taking and the clinical tests of balance function are hence very important to ensure that the clinician is on the right track and has not been deceived into unnecessarily prescribing anti-vertigo drugs in cases which are not exactly disorders of the balance system.
Vertigo, a type of dizziness, is the illusion of motion, usually rotational motion. Associated symptoms include nausea, emesis and diaphoresis. Vertigo should be distinguished from other types of dizziness, such as imbalance (dysequilibrium) and light-headedness (presyncope). Most cases of vertigo can be diagnosed clinically and managed in the primary care setting. As patients age, vertigo becomes an increasingly common presenting complaint.
Vertigo is an extremely common condition. It is very often a self limiting disorder which can be managed by the family physician. Only in a very few cases, would a referral to a specialist be required. However, in actual practice when the patient with vertigo goes to the family physician- he is immediately referred to the neurologist, ENT specialist or neurotologist, which is very often not required and is an undue harassment for the patient.
A brief physiology of the balance system
The balance system is a multi-organ, multi-system mechanism. Most medical specialists e.g. a cardiologist, an ophthalmologist or a gastroenterologist usually deals with only one particular system of the body, but for the neurotologist or the medical specialist who specializes in the management of balance disorders / vertigo, there are several body systems which are working together. These include:
• The central nervous system
• The peripheral nervous system
• The musculo-skeletal system
• The visual system
• The vestibular system
Over and above these main systems, other systems like the psychic system, the cardiovascular system and probably also the auditory system are also involved in the maintenance of balance and in disorders of any of these systems, the balance system gets screwed. Different systems of the body work in tandem to maintain the body’s balance. This is what makes the disorders of the balance system so complex and so very hard to diagnose and treat.
Maintenance of balance
How is the body’s balance maintained?
Nature has given us certain sensors which are spread in different parts of the body and these sensors inform the brain about the stability of the ground and the surroundings where the person is situated.
Once the brain comes to know about how stable the ground is or how stable are the surroundings, the brain evolves a motor output – thereby creating a contraction of different body muscles. As a result of the very precise and accurately timed contraction of the relevant muscles of the body, the body’s stability is restored thereby preventing a giddiness episode, instability or a fall. Starting from the sensors picking up the information about the stability of the ground and surroundings, its processing in the brain and the generation of the motor output, -transmission of the motor output through the peripheral nerves to the relevant muscles is quite a complex system involving many different organs of the body. The entire activity is like a reflex i.e a spontaneous action –very much like that of the rest of the body’s other reflex actions.
The figure represents the different reflex pathways by which the body’s balance is maintained. This picture is extremely important for us because when we discuss the diagnosis and management, these different aspects become very relevant. Like the other reflexes in the body, the maintenance of balance is also a reflex action with the involvement of a sensory organ, an afferent neuralpathway, a center of the reflex in the brain stem, an efferent neural pathway and an effector motor organ.
The afferent sensory organ such as the eyes, the vestibular organs in the ears and the proprioceptors (the sensors situated in different parts of the body such as the soles of the feet, or the neck) pick up information about the stability of the surroundings and that of the ground and pass it to the center of the reflex which is situated in the brain stem by an afferent neural pathway. For example the vestibular nerve is the afferent neural pathway for the information coming from the vestibular labyrinth. The center of the reflex is situated in the brain stem where the four vestibular nuclei are situated. The efferent neural pathway which comprises of neural tracts in the brain and spinal cord and the peripheral nerves carries the motor output to the different muscles of the body.
The three reflex pathways
The information from the three sources – the eyes, vestibular organs in the ears and the proprioceptors is integrated in the brain –giving the brain a perfect idea about the stability of the ground and the surroundings. The brain then evolves the motor output and this motor output will be directed to certain muscles of the body. It is directed basically to 2 groups of muscles. One group of muscles is the skeletal muscles of the limbs, the trunk and the neck and that works through the vestibulospinal pathway. This reflex system is known as the vestibulospinal reflex. The other group of muscles is the small muscles of the eyes and it works through the vestibuloocular reflex pathway.
Vertigo results from acute unilateral vestibular lesions that can be peripheral (labyrinth or vestibular nerve) or central (brainstem or cerebellum). In contrast, tumors and ototoxic medications produce slowly progressive unilateral or bilateral lesions. Lesions that progress slowly or processes that affect both vestibular apparatuses equally usually do not result in vertigo. Most common causes of this condition are Benign Paroxysmal Positional Vertigo (BPPV), Acute vestibular neuronitis or Labyrinthitis, Meniere’s disease, Migraine and anxiety disorders. Less common causes include Vertebrobasilar ischemia and retrocochlear tumors.
PERIPHERAL VESTIBULAR DISORDERS
Peripheral vestibular disorders are limited to cranial nerve VIII and all distal structures. Patients with a peripheral disorder demonstrate nystagmus to the contralateral side which suppresses with visual fixation. Nystagmus improves with gaze towards the lesion and worsens with gaze opposite the lesion. Patients may also report a falling sensation. Vegetative symptoms are not uncommon, and one can expect nausea, vomiting, and possibly sweating and bradycardia. The rate of recovery typically decreases with age and severity, and with the use of vestibulosuppressive medications
The term Meniere’s syndrome is often used synonymously with the terms Meniere’s disease (MD) and endolymphatic hydrops, although they are different. Endolymphatic hydrops describes an increase in endolymphatic pressure resulting in inappropriate nerve excitation which gives rise to the symptom complex of vertigo, fluctuating hearing loss, and tinnitus. The exact mechanism by which this increase in pressure produces the symptoms of MD is greatly debated and beyond the scope of this paper. Numerous disease processes can result in endolymphatic hydrops; if there is a known etiology then it is termed Meniere’s syndrome. MD is a term used for endolymphatic hydrops of unknown etiology. The true incidence of MD is unclear due to difficulty in diagnosis. Caucasians are more often affected, and it is more prevalent in females than males. Typically, these patients complain of spontaneous episodic attacks of tinnitus, aural fullness, fluctuating hearing loss, and vertigo superimposed on a gradual decline in hearing. Symptoms are variable, however, and patients may have a predominance of either cochlear (tinnitus, hearing loss) or vestibular (vertigo) complaints. Attacks typically last minutes to hours; however, most commonly subside after 2 to 3 hours. Diagnosis is established with a thorough history detailing the aforementioned complaints, possibly accompanied by nausea, vomiting, and diaphoresis. Audiologic and vestibular testing is unreliable, but may show caloric weakness on electronystagmography (ENG) and sensorineural hearing loss on audiography. There is no cure for MD and the goal of treatment is symptomatic relief. Medical treatment is initiated prior to more invasive surgical intervention and consists of salt restriction, diuretics, vasodilators, anti-emetics, and anti-nausea medications. Those who fail medical treatment may consider surgical therapy. Surgical treatments can be classified as either hearing-conservative or non–hearing-conservative procedures and are appropriately chosen based on the patient’s audiometric results. For patients with serviceable hearing, endolymphatic sac decompression, vestibular neurectomy, and intratympanic aminoglycoside infusion are options. Labyrinthectomy is reserved for patients with no serviceable hearing
BENIGN PAROXYSMAL POSITIONAL VERTIGO
Benign paroxysmal positional vertigo (BPPV) is considered the most common peripheral vestibular disorder, affecting 64 of every 100,000 Americans.Women are more often affected and symptoms typically appear in the fourth and fifth decades of life. In 1980, Epley proposed that free-floating densities (canaliths) located in the semicircular canals deflect the cupula creating the sensation of vertigo.3 This is well documented in his Canalithiasis Theory. Although these canaliths are most commonly located in the posterior semicircular canal, the lateral and superior canal may also be involved. Patients with BPPV complain of vertigo with change in head position, rolling over, or getting out of bed, and the vertigo is often side specific. Vertigo occurs suddenly and lasts for less than 1 minute. Attacks are separated by remissions; however, patients may complain of constant light-headedness between episodes. Classic BPPV involving the posterior semicircular canal is characterized by the following: geotropic nystagmus with the problem ear down, predominantly rotary nystagmus toward the undermost ear, latency of a few seconds, duration limited to less than 20 seconds, reversal of nystagmus when the patient returns to an upright position, and a decline in response with repetitive provocation. Diagnosis is made primarily through history and also by eliciting typical physical findings during the Dix-Hallpike maneuver. The Dix-Hallpike maneuvre entails guiding a patient through a series of movements known to elicit nystagmus in a patient with BPPV. Electro-oculography and 2D videonystagmography are of limited use secondary to the inability of these tests to record torsional eye movement. Treatment is often supportive as a large percentage of patients will have spontaneous resolution of their symptoms. For those with persistent symptoms, the first line of treatment is canalith repositioning maneuvers. These maneuvers attempt to reposition the free-floating canalith particles from the semicircular canals to the utricle using gravity. These maneuvers are reported to be 91% effective. Patients with symptoms refractory to repositioning maneuvers may be candidates for singular neurectomy or posterior semicircular canal occlusion.
Vestibular neuronitis is the second most common peripheral cause of vestibular vertigo. Infection of the vestibular nerve results in nerve degeneration and may present bilaterally. Infection is most often thought to be of viral origin, usually from the herpes virus family. It may also result from bacterial invasion (e.g. Borrelia). It is believed that the superior vestibular nerve is more commonly involved secondary to its course throughout a long and narrower bony canal, making it more susceptible to compressive edema. The reported incidence of an upper respiratory infection prior to the development of vestibular symptoms varies from 23% to 100%.
Patients present with complaints of sudden vertigo, lasting up to several days, often with vegetative symptoms. As this process affects only the vestibular portion of the vestibulocochlear apparatus, there is an absence of cochlear symptoms. Vertiginous complaints gradually improve over days to weeks; however, imbalance may persist for months after resolution of acute disease. Recurrence is not uncommon and may occur several times per year. Physical examination is limited and should consist of audiometric evaluation and ENG. Patients may demonstrate nystagmus and caloric weakness on the affected side. Treatment is primarily supportive with the use of anti-emetics and anti-nausea medications. Vestibular suppressants should be used judiciously in the first few days of an acute attack. Prolonged use of these medications can delay recovery by inhibiting central compensation.
Furthermore, early ambulation is paramount in the central nervous system’s ability to compensate and is therefore recommended as soon as tolerable. High-dose methylprednisone has been shown to hasten recovery; however, prospective, randomized, double-blinded studies have failed to demonstrate added benefit from the use of antivirals (i.e. valacyclovir).
Labyrinthitis is an inflammatory disorder of the membranous labyrinth, affecting both the vestibular and cochlear end organs. It may present unilaterally or bilaterally, and similar to vestibular neuronitis, it is often preceded by an upper respiratory infection. This disorder occurs when infectious microorganisms or inflammatory mediators invade the membranous labyrinth, damaging the vestibular and auditory end organs. Potential etiologies include viral pathogens, bacterial invasion, bacterial toxins, and systemic disease. Viral labyrinthitis usually occurs in adults in their fourth to seventh decades of life. Bacterial Labyrinthitis may result from both otogenic and meningitic infection, progressing to involve the labyrinth. Labyrinthitis of otogenic origin can be observed in any age group and may result from cholesteatoma or otitis media. Meningitic labyrinthitis is more common in children less than 2 years of age, who are more susceptible to developing meningitis. Otogenic infections typically cause unilateral symptoms while meningitic infections cause bilateral symptoms. Unlike vestibular neuronitis, patients with Labyrinthitis present with complaints indicative of both vestibular and cochlear damage. Vertigo presents suddenly and is accompanied by hearing loss. ENG may reveal nystagmus, and audiometry will reveal a sensorineural hearing loss or mixed hearing loss if middle ear effusion is present. Depending on the source of infection, patients may also present with findings consistent with otitis media, mastoiditis, or meningitis. Treatment is aimed primarily at eradication of the underlying infection and supportive care. Middle ear effusions and mastoiditis should be drained and treated with antibiotics. Meningitis should be treated with culture-directed antibiotics with central nervous system penetration and appropriate consultation. Anti-emetics and anti-nausea medications are helpful during the acute phase.
TREATMENT OF VERTIGO
Treatment of acute vertigo consists of bed rest (1-2 days maximum) and vestibular suppressant drugs such as Antihistaminics (Meclizine, Dimenhydrinate), molecules with GABA-ergic effects (Clonazepam, Diazepam), Phenothiazines (Prochlorperazine) etc. If vertigo persists beyond a few days, most authorities advise ambulation in an attempt to induce central compensatory mechanisms, despite the short term discomfort to the patient. Chronic vertigo of labyrinthine origin may be treated with a systematized vestibular rehabilitation program to facilitate central compensation. BPPV is often self-limited but, when persistent, may respond dramatically to specific repositioning exercise programs (Epley maneuvre) designed to empty particulate debris from posterior semi circular canals.
Medical management or pharmacotherapy of vertigo:--
The objectives are :
* Provide symptomatic relief —palliative therapy to reduce the vertigo.
* Increase cerebral and inner ear blood flow —one of the many causes of vestibular damage is hypoxia. Hypoxia of the brain and the inner ear induces a degenerative change which has to be prevented.
* Increase active transport through blood brain barrier —to maintain inner ear homeostasis. The ionic concentration of the different ions in the cells and the volume of fluid in the intracellular and extra cellular compartment have to be kept at an optimum and specified fixed level.
* Improve neural metabolism —supply nutrients to the neuronal tissues to protect the inner ear cells and the neural cells and prevent further damage.
Ideal anti vertigo drug is one that will:-
• Control the vertigo and or instability as well as nausea and vomiting
• Enhance the cerebral and inner ear blood flow
• Be reasonably safe and free from side effects
• Not depress the vestibular compensatory mechanism.
Symptomatic relief of vertigo is best brought about by:-
Control of nausea/vomiting by:-
Mechanism of action:--
The control of vertigo is brought by the anticholinergic drugs and the nausea/vomiting is controlled by antidopaminergic drugs. The anticholinergic drugs control the vertigo by blocking the muscurinic receptors in the higher vestibular pathways. The transmission of neural impulses in the vestibular system is done by cholinergic pathways where these muscurinic receptors are located. If these muscurinic receptors are blocked, then the neural impulses cannot pass through these neural pathways. Blocking of the dopamine receptors in CTZ (chemoreceptor trigger zone) controls nausea and vomiting. The problem of giving anticholinergic drugs is that the cholinergic transmission through muscarinic receptors is present in many CNS pathways and other body tissues. There is no known anticholinergic / antimuscarinic drug that acts solely and exclusively in the vestibular pathways only. If you give anticholinergic therapy, it will block the transmission in all the cholinergic pathways, so the patient gets many other symptoms also. That is the main problem of giving symptomatic treatment to the patient. But when the patient gets acute vertigo, we need to give symptomatic relief also. So we have to find out how much to give and how much not to give.
Let us discuss the pros and cons of some of the commonly used drugs in vertigo
Commonly used drugs in vertigo:--
Dimenhydrinate This is best for a patient who is having acute vertigo with vegetative symptoms like nausea/vomiting/sweating. This is an anti cholinergic drug like Prochlorperazine; its efficacy for giving symptomatic relief is less than that of Prochlorperazine, yet it provides reasonably good relief. It has been found to act best in the pathway from the vestibular nucleus to the reticular formation in the brain stem. The vegetative centers are there in the reticular formation. Dimenhydrinate partially helps to inhibit the projection of neural impulses from the vestibular nuclei to the reticular formation where the vegetative centers are situated. Thus if a patient is having severe vertigo with nausea and vomiting, which you are not able to control adequately with Prochlorperazine, then you can add a drug like Dimenhydrinate (marketed in the name of Gravol) 50mg thrice daily. Thus it is the drug of choice in acute vertigo with pronounced vegetative symptoms. It is however a CNS depressant, and is hence best discontinued as soon as acute symptoms subside. Its anti-emetic effect is not associated with extra-pyramidal symptoms.
Diazepam is also not very uncommonly used in the management of acute vertigo as it gives very good relief from vertigo. In those rare cases where acute vertigo is not being controlled by Prochlorperazine, Diazepam can be tried; but the problem of Diazepam is that it is a CNS depressant which will completely jeopardize the vestibular compensatory mechanism. So it can be used only for one or two doses at the most just to tide over the very acute phase and Prochlorperazine can then be continued for about 7 days. Another advantage of diazepam is its anxiolytic effect; moreover it not only controls the vertigo but partially also the accompanying nausea & vomiting.
Prochlorperazine (Stemetil 5mg tds): ---This is very effective in fact the most efficient drug for symptomatic relief. It acts on the muscurinic receptors and blocks the dopamine receptors in the brain and hence not only controls the vertigo but also the nausea and vomiting. It is but a CNS depressant like all the other anticholiinergic drugs; hence it is likely to inhibit the vestibular compensatory mechanism. This is true if you are using the drug for very prolonged periods because there are clinicians who use it for 3, 4 and 5 months or even more. Prochlorperazine is basically a drug which gives symptomatic relief; and once symptomatic relief has been obtained the other things will naturally fall into place. Controlling the symptoms for 5 or 7 days with this drug is ideal as it provides very good symptomatic relief. After the symptoms have been adequately controlled the patient should essentially be put on the vestibular exercises for the natural compensation to take place . The patient may be asked to keep two Stemetil MD(prochlorperazine mouth dissolving) tablets with him so that when he feels the vertigo he may suck a tablet or two. It gives instant relief.
Cinnarizine 25-75 mgs tds has a labyrinthine sedative effect. It has an antivasoconstrictive effect also. It increases the cerebral and inner ear blood supply; stabilizes the vascular endothelium and is a reasonablly safe drug. But it does not give the same symptomatic relief as Prochlorperazine. If you are having a very old aged patient who is expected to have hypoxia in the brain gets vertigoon and off, then you can think of putting the patient on Cinnarizine for some time, as it will increase the blood supply to the brain and inner ear and at the same time provide some symptomatic relief. But it does not make sense to give Cinnarizine to a young or middle aged patient with sudden onset of severe vertigo as here we are only wanting symptomatic relief in acute vertigo for which prochlorperazine is a better drug. Our objective is just symptomatic relief and not increase of blood supply as in such cases hypoxia of the brain/inner ear is not the expected pathology. Acute onset of severe vertigo is usually due to unilateral vestibular lesion and here our main objective is providing symptomatic relief for a few days as the condition is usually self-limiting and compensation is expected to take place naturally by itself.
Betahistine 8-16 mg tds 24mg bd: -- Like cinnarazine, betahistine also offers some symptomatic relief which of course is lesser than prochlorperazine (if betahistine is prescribed at the usual dose of 48 mg daily) and it also increases the blood supply to the brain and inner ear. The advantage of betahistine is that it is the only non-sedating anti-vertigo drug and is not a CNS depressant and so does not jeopardize the compensatory mechanism. It is ideal for a patient of uncompensated persistent subacute vertigo in a vasculopathic subject ( with suspected cerebral / inner ear hypoxia) where the primary aim is vestibular compensation. It is recommended in Meniere’s disease.
Meclizine:- This is not used much in our country. It is sold in the name of Diligan. The exact mechanism of this drug is not known. Like other antihistamines of H1 antagonistic group, anticholinergic activity and monoaminergic enhancing effect, believed to diminish excitability of neurons in vestibular nucleus. Meclizine is unfortunately a strong CNS depressant. It does not increase the cerebral and inner ear blood flow. It is more suited for motion sickness than for acute vertigo.
Getting to know the molecule: BETAHISTINE
This drug (brand name Serc, chemical name betahistine), is advocated as a vestibular suppressant mainly for Meniere's disease. Curiously, Serc was approved by the US FDA about 40 years ago for roughly 5 years, but later approval was withdrawn because lack of evidence for efficacy and because the major report of effectiveness contained deficiencies and misrepresentations (Sampson, 2003). The withdrawal was upheld by a US court of appeals in 1968. Subsequently, four double-blind studies have been done reporting reduction of vertigo attacks with betahistine (Frew and Menon, 1976: Wilmot and Menon; 1976; Meyer, 1985; Mira et al, 2003). Nevertheless, these studies may have been flawed and a recent review suggested that it is presently still unclear if betahistine has any effect in Meniere's disease (James and Burton, 2001).
Serc was again reviewed by the FDA in June of 1999 (click herefor details). Essentially, the conclusion was that there is no evidence that it is harmful, but also little evidence that it has any therapeutic effect. It thus is similar in official status to an inert substance. Serc has been reviewed by the "Cochrane database", who concluded in 2009 that "There is insufficient evidence to say whether betahistine has any effect on Ménière's disease"
At the time of this update (2/2010), we generally just send patient to Walgreens. Betahistine can also be easily obtained through US compounding pharmacies, with a prescription. It is difficult to see why an inert substance must be prescribed, but nevertheless, this is the situation in the US. Insurance often covers betahistine too.
Rationale for use of Betahistine:
For those who want the quick answer, nobody has a reasonable rationale of why betahistine should work for dizziness. Following is the longer explanation.
Although betahistine does not closely resemble histamine (see above), in the body it is a histamine agonist. There are 3 histamine receptors - -H1, H2 and H3. The rationale for its use is somewhat difficult to understand as H1 blocking antihistamines (such as meclizine) are also used quite commonly to treat vertigo. Explanations commonly given are that the drug is a vasodilator, or that it acts on subreceptors of histamine. H1 and H2 are post-synaptic receptors and H3 is a pre-synaptic receptor. Betahistine is a potent H3 receptor antagonist. (Lacour and Sterkers, 2001). Stimulation of the H3 receptor reduces histamine release, so antagonism of H3 increases histamine release. H3 receptors control the synthesis and release of histamine via a Gs protein (de Waele et al, 1995).
According to de Waele et al (1995), there are several lines of evidence that suggest that histamine receptors modulate the function of central vestibular neurons. One influence is via axons from the posterior hypothalamus. This may be related to wakefulness as histamine controls wakefulness. Both H1 and H2 binding sites have been detected in vestibular nuclei. These authors note that there is data suggesting both that H1 and H2 actions are excitatory on the vestibular nucleus, and that common H2 blocker drugs such as cimetidine antagonize the effect. This suggests that H2 blockers (commonly used to reduce stomach acid), at least those that cross into the brain, may have a central vestibular suppressant effect. H3 antagonists appear to inhibit horizontal vestibular gain without affecting alertness. This line of reasoning does not explain at all why betahistine would be helpful -- one would even think that it would be harmful if it excites the vestibular nucleus. This is just one example of the large array of confusing literature about this drug.
Most antivertigo drugs are H1 blockers. Many newer allergy medications are selective peripheral H1 blockers, and many older allergy medications, including those used for dizziness such as dramamine, are peripheral and central H1 blockers. Many medications for stomach problems that block acid are H2 blockers, but these are not generally thought to affect vestibular function (see above however).
Betahistine is an H3 antagonist, according to Timmerman (1991). H3 antagonism is felt to increase H1 and H2, so the net effect of H3 antagonism is histamine (H1 and H2) agonism. Confusingly though, some authors suggest that betahistine is an H3 agonist. The neuropharmacological literature is also complex. Arrang et al (1985) found betahistine to be a partial agonist against cerebral H1 receptors, and has no effect on H3 receptors. In other words, some H3 agonists might block histamine release, but betahistine (betahistine) doesn't affect these receptors in guinea-pigs. This would suggest that either betahistine is a placebo, or that it's effects result from some mechanism other than H3.
As mentioned above, it seems contradictory that both H1 blockers (meclizine) and H1 agonists (betahistine) are advocated for vertigo. It, however, is possible that the antihistamine effects of meclizine are less important than its anticholinergic effects, so there may not be a contradiction between the H1 effects. The general thought at the present is that the effects of betahistine relate to it's effect on H3 receptors, although what exactly this effect is still rather mysterious. If betahistine is indeed an H1 agonist and an H3 antagonist, it might suppress vestibular function and enhance alertness, both valuable qualities. By this thinking, betahistine could be reasonably combined with a selective H1 blocker that does not cross into the brain (such as fexofenadine).
Is it reasonable to combine meclizine (a central H1 blocker) and betahistine (a central H1 agonist) ? Well, perhaps if you are hoping to use the central anticholinergic properties of meclizine. It would see a more logical, however, to use a pure anticholinergic agent such as scopolamine instead of meclizine. Similarly, it seems reasonable to combine betahistine with a contemporary non-sedating antihistamine, as these medications do not cross the blood brain barrier.
Does it work ?
The author of this review has had moderate success with giving betahistine to patients who have intractable Meniere's disease, and it part of his usual regimen for intractable Meniere's (often in combination with verapamil). It comes in doses of 8, 16 and 24 mg.The usual dose is 16 mg 3-4 times per day although greater effect is obtained for doses as high as 48 mg at a time (Strupp,et al. 2008). Most people that report a positive effect can decide this with a few days -- it doesn't seem to take 1 month to figure out whether betahistine is helping or not.
The author also uses Betahistine to treat severe motion intolerance (e.g. Matsnev and Sigaleva, 2007). Betahistine can be used in children (Gryczynska, Drobik-Wasiewicz et al. 2007). While claims have been made that Betahistine is associated with weight loss, these appear to be unfounded (Barak, Greenway et al. 2008).
There are numerous puzzling aspects to betahistine and the jury is still out regarding whether or not it is an effective medication. Some studies report that betahistine cannot be distinguished from placebo. There are also some troublesome reports comparing betahistine to other medications that are almost certainly placebos, that can be interpreted in the same way. Klein et al (1998) reported that a homeopathic medication was equivalent in efficacy to betahistine. As homeopathic medications are generally felt to be placebos because of the extremely high dilutions with which they are administered, this suggests that either the Klein study was flawed, or that betahistine is also a placebo. On the other hand, Fujino et al (1994) reported betahistine to have a positive effect when combined with rehabilitation.
Side-effects are generally minimal. The author of this review has encountered stomach upset in several, worsening asthma, headache (Barak et al, 2007), and chest tightness as side-effects. Of course, these symptoms could be found in a placebo.
Post-marketing studies conducted by the manufacturer suggest only a very small number of adverse effects (Jeck-Thole et al, 2006). In theory, stomach upset might be related to H2 agonism, as H2 blockers are used to treat gastric acidity. Against this idea is that betahistine is not a H2 agonist, but the increased release of histamine associated with h3 antagonism might stimulate H2. As mentioned above, it seems reasonable to combine betahistine with a selective H2 blocker that does not cross the blood brain barrier, or a proton pump inhibitor used for gastric acidity. Headache might also be a direct effect of histamine. On the other hand, some studies report reduction of headache by betahistine (Amelin et al, 2003).
In it's favor, betahistine does not cause drowsiness and has no effect on driving, reaction time or visual acuity (Betts et al, 1991)
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