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Serc (betahistine)

Timothy C. Hain, MD

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Smith reported that 94% of the ENT surgeons in the United Kingdom prescribe betahistine to their Meniere's patients (Smith et al, 2005)

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 Curiously, Serc was approved by the US FDA about 40 years ago for roughly 5 years, but later approval was withdrawn because lack of evidence for efficacy and because the major report of effectiveness contained deficiencies and misrepresentations (Sampson, 2003).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 here for 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". A recent study of hydrops found that Serc had no effect (Gurlov et al, 2012).


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:


Histamine 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 4 histamine receptors, namely H1-4. 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. H4 is exitatory to the peripheral vestibular neurons. 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). Serc's H4 action probably is meaningless as it is not very powerful (Desmadryl et al, 2012).

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. To our knowledge, this potential use has never been exploited.

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. 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. Many 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. Fujino et al (1994) reported betahistine to have a positive effect when combined with rehabilitation.

Side Effects

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). See this outside link for more information.

In it's favor, betahistine does not cause drowsiness and has no effect on driving, reaction time or visual acuity (Betts et al, 1991)

Betahistine may be associated with weight loss. The reason is that centrally acting antihistamines seem to cause weight gain (Hampton, 2007), and by the same token, histamine agonists may cause weight loss. According to a study of Barak, weight loss (averaging 4.24 kg) was confined to women below the age of 50. (Barak et al, 2008).

According to Vlastarakos et al. (2008), Betahistine is contraindicated in pregnancy. While we agree that it is prudent to avoid use of drugs lacking rigorous data in pregnancy, the advice in this case does not appear to be supported by any adverse event data.

Incompatibilities ?

Little has been published on this subject. If one believes in the histamine agonism mechanism, it would make little sense to take a centrally acting antihistamine medication with betahistine as the betahistine might not work. This covers a lot of ground including many conventional "dizziness" drugs. A person on betahistine should be able to take purely "peripheral" acting antihistamines (such as Claratin, Allegra and Zyrtec). Similarly a person on betahistine should not take antidepressants with central antihistamine side effects such as the "tryptylines". This includes Elavil and Pamelor. Practically, we have not noted any interaction problems.



Copyright October 6, 2013 , Timothy C. Hain, M.D. All rights reserved. Last saved on October 6, 2013