Acta Oto-Laryngologica.

2015; 135: 1205–1211

REVIEW

Use of betahistine in the treatment of peripheral vertigo

RUBÉN RAMOS ALCOCER1, JOSÉ GREGORIO LEDEZMA RODRÍGUEZ2,

ANTONIO NAVAS ROMERO3, JOSÉ LUIS CARDENAS NUÑEZ4,
VICENTE RODRÍGUEZ MONTOYA5, JOSE JUNIOR DESCHAMPS6 &
JORGE ANIBAL LIVIAC TICSE7
1
Otorrinolaringologo y Neurotologo, Medicentro del Parque, San Luis Potosí S.L.P, México, 2ORL, Otoneurología,
Fundación Venezolana de Otología, Instituto de Otorrinolaringología y Oftalmología, Hospital Militar Dr Carlos Arvelo,
Caracas, Venezuela, 3Médico Otorrinolaringólogo-Neurootólogo, Servicio de ORL, Dirección General de Aviación Civil,
Director de la clínica del vértigo y acúfenos, Quito, Ecuador, 4Profesor Titular de Neurologia, Facultad de Ciencias
Médicas, Universidad de Santiago de Chile, Centro de Medicina Aeroespacial, Fuerza Aérea de Chile, Las Condes,
Santiago de Chile, 5Otorrinolaringólogo-Otólogo, Clínica del Country, Clínica La Colina, Bogotá, Colombia, 6Centro de
Otorrinolaringología y Especialidades, Universidad autónoma de Santo Domingo, República Dominicana and
7
Neurología, Clínica privada Jorge Anibal Liviac Ticse, Lima, Peru

Abstract
Conclusion: Clinical studies and meta-analyses demonstrated that betahistine is effective and safe in the treatment of Ménière’s
disease, BPPV (benign paroxysmal positional vertigo), vestibular neuronitis, and other types of peripheral vertigo. Objectives:
The goal of this paper is to review the pharmacological profile of betahistine and the evidence for its effectiveness and safety in
the treatment of peripheral vertigo. Methods: Selection criteria for the publications on betahistine included randomized clinical
trials that evaluated the effectiveness and safety of betahistine vs placebo or active control in the treatment of peripheral vertigo.
Recent meta-analyses were also included. Databases searched included PubMed, the Cochrane Ear, Nose and Throat
Disorders Group Trials Register, and ICTRP. The review also presents an update on the mechanisms of action, pharma-
codynamics, and pharmacokinetics of betahistine. Results: Efficacy and safety of betahistine has been demonstrated in
numerous clinical trials. The precise mechanism of action of betahistine is still not completely understood, but the clinical
experience demonstrated the benefit of betahistine in different types of peripheral vertigo. In more than 40 years of clinical use,
betahistine has shown an excellent safety profile with the usual dose range from 8–48 mg daily. According to clinical studies,
betahistine 48 mg daily during 3 months is an effective and safe option for the treatment of peripheral vertigo.

Keywords: Ménière’s disease, benign paroxysmal positional vertigo, neuronitis, vestibular compensation, treatment, prevention

Introduction vomiting, sweating) or auditory symptoms (hearing

loss, tinnitus, feeling of ear fullness) [1–4].
Vertigo is a term that refers to an illusion of self or Vertigo is one of the most common symptoms
environmental motion, typically described as spinning which patients present to physicians. It has been
or whirling. The sense of motion is generally rotatory, estimated that the annual prevalence of vertigo is
but it may also be linear. Usually it produces some 4.9% for the general population, and the lifetime
sense of disorientation in space, and it may also be prevalence of vertigo is ~ 20–30% [2–4]. Vertigo is
accompanied by vegetative disturbances (nausea, reported ~ 1.7-times more often by women than by

Correspondence: Rubén Ramos Alcocer, Otorrinolaringologo y Neurotologo, Medicentro del Parque, calle Jesus Goytortua 106 int. 203, colonia Tangamanga
CP 78269, San Luis Potosí S.L.P, México. Tel: +444-817-4400. E-mail: [email protected]

(Received 27 May 2015; accepted 8 July 2015)

ISSN 0001-6489 print/ISSN 1651-2251 online  2015 Informa Healthcare
DOI: 10.3109/00016489.2015.1072873
1206 R. Ramos Alcocer et al.

men, and visits to the doctor’s office because of all of the drug therapies [13,9–11]. Although the
vertigo increase with age [4,5]. precise mechanism of action of betahistine is still
Vertigo always reflects dysfunction at some level of not fully understood, the clinical experience demon-
the vestibular system, and, according to the topo- strated the benefit of betahistine for different types of
graphic origin of the disturbance, it may be classified peripheral vertigo. The goal of this paper is to review
as peripheral or central [24]. The most common the pharmacological profile of betahistine and the
causes of vertigo are peripheral vestibular disorders, evidence for its efficacy and safety in the treatment
but central nervous system disorders must be of peripheral vertigo [1,2,10,11].
thoroughly assessed and excluded in each patient.
Epidemiologic studies indicate peripheral causes of Pharmacology of betahistine
vertigo are responsible for almost three-quarters of the
vertiginous attacks experienced by patients, while Betahistine is a histamine modulator that, based on
one-quarter may be related to central or mixed causes clinical experience, is used in adults for the treatment
[1–4]. of Ménière’s disease and BPPV. The precise mech-
The most frequent cases in clinical practice are anism of action is not well known, but clinical expe-
benign paroxysmal positional vertigo (BBPV), rience demonstrated that it can prevent the evolution
Ménière’s disease, and vestibular neuritis. Relative of Ménière’s disease and, according to some authors,
frequency depends on case definition and diagnosis progressive hearing loss. In BPPV it is used primarily
criteria in surveys or clinical trials, but ~ 15–20% of as a coadjuvant of vestibular compensation for cases
vertiginous attacks are considered BPPV, 10–12% with recurrent disease [9–15].
Ménière’s disease, and 8–10% vestibular neuritis Pathophysiology of Ménière’s disease shows a mis-
[1,2]. Vestibular neuritis is also called vestibular neu- balance between the influx and efflux of fluids that
ronitis or labyrinthitis by some authors, and there is leads to an alteration of the endolymphatic pressures,
no clear consensus for which term should be used or if which in turn causes endolymphatic hydrops. It is
they are truly interchangeable [1,2]. considered that betahistine regulates capillary
The treatment of vertigo requires an integral and structures in the stria vascularis of the inner ear,
multi-modal approach. Treatment usually includes reducing the pressure in the endolymphatic space,
the use of medication, physical therapy, and lifestyle and facilitating the reabsorption of endolymphatic
adaptations. Canalith repositioning maneuvers such fluid [12–15].
as the Epley maneuver and/or Brandt-Daroff exercises In the majority of cases of BPPV the etiology is
are commonly used [1–8]. Physical therapy is targeted unknown and it may follow vascular disorders or head
to promote vestibular compensation, a natural trauma. It is considered that otoconia may be
process of behavioral recovery after a peripheral ves- detached and released in these cases and the recur-
tibular lesion [8,9]. Many patients may also benefit rence of BPPV is thought to be caused by vascular
from support psychotherapy, while a small number of disorders. Betahistine produces vasodilatation and
patients with highly severe and recalcitrant disease improves microcirculation of the inner ear. These
may need surgical treatment [1–10]. mechanisms may probably explain the effectiveness
There are many forms of medical treatment. The of betahistine as a coadjuvant of vestibular compen-
most common group of drugs used in the treatment of sation in recurrent cases of BPPV [9–15].
vertigo are diuretics, antiemetics, steroids, antivirals, In vestibular neuronitis the firing of neural impulses
antimicrobials, calcium channel blockers, antidepres- is disrupted at central level by circulatory alterations,
sants, anticonvulsants and aminopyridines. The eti- and probably betahistine may be effective by improv-
ology and physiopathology of Ménière’s disease, ing microcirculation of the inner ear. The effects on
BPPV and other types of peripheral vertigo are not the inner ear and on the Central Nervous System may
fully understood. As a result, it is not possible to know both collaborate to reduce the time of adaptation.
the exact mechanism of action of drugs used in Therefore, although there is no first grade evidence of
these disorders. In clinical practice, histaminergic the efficacy of betahistine, clinical experience and
drugs are the most widely prescribed for the treatment numerous clinical studies support the effectiveness
of peripheral vertigo, although the molecular mechan- and safety of betahistine in different types of
isms by which histamine modulates vestibular peripheral vertigo [12–15].
function remains unclear [5–11].
Betahistine is a histamine modulator that has been Pharmacodynamics
employed in the treatment of peripheral vertigo for
more than 40 years [9–11]. In European countries, The primarily action of betahistine is to modulate the
betahistine is the most frequently chosen drug among histaminergic system. It has a strong activity as an
 Betahistine in the treatment of peripheral vertigo 1207

antagonist for histamine H3 receptors and a weak Elimination of betahistine takes place mainly by
activity as an agonist for histamine H1 receptors, metabolism. After absorption, betahistine is rapidly
with virtually no activity on H2 receptors [10–15]. and almost completely metabolized into 2-PAA. The
In the inner ear, betahistine has a potent antagonistic concentration of 2-PAA reaches its peak 1 h after
effect at H3 receptors, and increases the levels of ingestion and declines to half in ~ 3.5 h by renal
neurotransmitters released from the nerve endings. excretion. No unchanged betahistine has been
It also has a direct agonistic effect on H1 receptors recovered in urine analyses [12–14].
located on blood vessels in the inner ear. The increased In pharmacokinetic analyses with an oral dose
amounts of histamine released from histaminergic range between 8–48 mg, ~ 85% of the original dose
nerve endings stimulates H1 receptors, thus augment- was recovered in the urine and the recovery rates were
ing the direct agonistic effects of betahistine on these constant. This suggests that the pharmacokinetics of
receptors. This explains the potent vasodilatory effects betahistine is linear, and potential metabolic pathways
of betahistine in the inner ear and the efficacy of are not saturated throughout the dose range com-
betahistine in the treatment of vertigo [1,2,10–15]. monly used in clinical practice [12–14].
Betahistine may increase blood flow in the cochlear
region, probably by means of a relaxation of the Safety
pre-capillary sphincters of the microcirculation in
the inner ear. It appears to act on the pre-capillary Betahistine is contraindicated for patients with pheo-
sphincters in the stria vascularis of the inner ear, chromocytoma. People with bronchial asthma and a
reducing the pressure in the endolymphatic space history of peptic ulcer need to be closely monitored.
[10–15]. Most frequent adverse effects are headache and mild
Betahistine promotes and facilitates vestibular gastric alterations like nausea, vomiting, dyspepsia,
compensation. This effect is probably caused by an abdominal pain, and abdominal distension. In
up-regulation of histamine turnover and release medi- placebo-controlled clinical trials, incidence of adverse
ated through the H3 receptor antagonism. It also events and discontinuation rates in general have been
demonstrated a dose-dependent inhibiting effect on similar among betahistine and placebo groups. No
spike generation of neurons in lateral and medial serious adverse events have been reported with the
vestibular nuclei, by which betahistine modifies neu- use of betahistine. Adverse reactions are usually mild,
ronal firing in the vestibular nuclei. The efficacy of temporary, and can be dealt with by lowering the dose
betahistine in Ménière’s disease may be due to its or by taking the dose during meals [1–3,5,10,11,16].
ability to modify the circulation of the inner ear or
due to a direct effect on neurons of the vestibular Clinical use of betahistine
nuclei [12–15].
Initial treatment with betahistine in adults is usually in
Pharmacokinetics the range of 8–16 mg 3-times daily, and maintenance
doses normally range from 24–48 mg daily. Dosage
Betahistine is rapidly and almost completely absorbed can be adjusted according to response to treatment.
after oral administration. Maximum plasma concen- Improvement could be observed after a couple of
trations (Cmax) are achieved after ~ 1 h of oral weeks of treatment, but usually better results are
administration in fasting subjects. Under fed observed after 1–6 months of therapy [1,2,9–15].
conditions, Cmax is lower, but total absorption of Effectiveness of betahistine has been demonstrated
betahistine is similar. Thus, food intake merely slows to be dose-dependent and time-dependent. In con-
down the absorption process, but does not impair the sequence, the appropriate dosage and duration of
total absorption of the drug. The fraction of betahis- treatment are key components of therapy success.
tine that is bound to plasma proteins is estimated to be According to most clinical experiences, 48 mg daily
less than 5% [12–14]. during 3 months seems to be the most successful
Betahistine is transformed, mainly at the hepatic therapeutic scheme for Ménière’s disease and other
level, in aminoethylpyridine (M1), hydroxyethylpyr- types of peripheral vertigo. This dosage has been
idine (M2), and, finally, in 2-pyridylacetic acid shown to be useful in order to control symptoms,
(2-PAA) (M3). All these substances are present in reduce frequency and intensity of attacks, facilitate
the body fluids of subjects treated with betahistine, vestibular compensation, improve quality-of-life, and
and, thus, might have pharmacological effects, prevent new episodes [1–3,10,11,16,17].
although the main hypothesis derived from animal Although a recent Cochrane review concluded that
models is that the anti-vertigo action of betahistine is there is insufficient evidence to confirm the effects of
at first achieved by betahistine itself [12–14]. betahistine on Ménière’s disease [5], effectiveness and
1208 R. Ramos Alcocer et al.

safety of betahistine has been demonstrated in many In this trial, the most remarkable effect of betahis-
clinical trials [9,15,17–20], clinical reviews, and tine was a considerable improvement of vertigo,
meta-analysis [1,2,10,11,16]. judged both by the patients’ score cards and by the
There are some reports about the efficacy of clinical assessment of the investigator. Audiograms
betahistine with higher doses, for example, up to demonstrated an improvement of hearing due to
144 mg/day, but, since these are off-label doses, betahistine, a finding which was supported by the
they will not be revised here [6]. patients’ own scores. An improvement with respect
There is limited data in children and adolescents. to tinnitus was also observed. All these results were
Therefore, betahistine should be used with caution in substantiated by statistical significance in favor of
these populations. Although there are limited data betahistine, and no adverse reactions were observed.
from clinical studies in geriatric patients, extensive In summary, in this trial there was a statistically
clinical experience suggests that no dose adjustment is significant improvement in favor of betahistine with
necessary [5,10,11]. regard to vertigo, tinnitus, and sensori-neural hearing
There are no specific clinical trials available in loss; and vertigo was the most responsive symptom
patients with renal or hepatic impairment, but, [9].
according to clinical experience, no dose adjustment The efficacy and safety of betahistine was assessed
appears to be necessary for these patients [5,6,10,11]. in patients with recurrent vertiginous attacks that
There is a limited amount of data from the use of received a diagnosis of Ménière’s disease or paroxys-
betahistine in pregnant women or during lactation. mal positional vertigo of probable vascular origin.
Therefore, it seems advisable to avoid the use of This placebo-controlled multi-center study con-
betahistine or to conduct a careful benefit-risk ducted by Mira et al. [15] at the Department of
evaluation before using betahistine in pregnant or Otorhinolaryngology of the University of Pavia, Italy,
lactating women [5,9–15]. enrolled a total of 144 patients from 11 centers in
Italy. The double-blind, parallel-group study
Betahistine in Ménière’s disease randomized patients to receive either placebo or
betahistine (16 mg twice daily) for 3 months. Of
Efficacy and safety of betahistine has been demon- the 144 patients enrolled, 75 were randomized to
strated in numerous clinical trials [9–11,15–20]. betahistine and 69 to placebo [15].
Frew and Menon [9] performed a pioneer placebo- Efficacy of interventions was determined by the
controlled clinical trial to assess the efficacy and safety frequency, severity, and duration of vertigo episodes,
of betahistine hydrochloride in Ménière’s disease. the GISFaV (Gruppo Italiano di Studio per la Farm-
The goal of this investigation was to evaluate the acologia della Vertigine) self-rating scale, DARS
effect of betahistine on the symptoms of Ménière’s (Dizziness Assessment Rating Scale), and DHI
disease in a double-blind, placebo-controlled, cross- (Dizziness Handicap Inventory).
over trial during 9 months [9]. After 3 months of therapy, betahistine significantly
Twenty-eight patients with Ménière’s disease were reduced the number of vertigo episodes, their inten-
admitted to the trial carried out in the Newcastle sity score, and their duration compared to placebo
University Hospitals Group, UK. Diagnosis was both in Ménière’s disease and PPV. The mean num-
based on paroxysmal attacks of rotational vertigo, ber of monthly vertigo attacks was reduced with
tinnitus, and fluctuating sensori-neural deafness. betahistine, both in Ménière’s disease (from 6.70 ±
Nausea and vomiting with the attacks were common. 9.56 at baseline to 2.06 ± 2.78 in month 3) and in PPV
The age of patients ranged from 28–63 years (from 6.90 ± 14.41 at baseline to 1.91 ± 3.51 in month
(mean = 45 years), and the duration of illness ranged 3); the statistical significance in comparison to pla-
from 2–20 years (mean = 7 years). cebo was detected from the first month of treatment
After pre-treatment periods of 4 weeks on placebo, (p < 0.05 for Ménière’s disease and p < 0.02 for PPV)
patients entered, on a randomized and double-blind (Figure 1).
basis, a cross-over trial of four 8-week periods. Beta- Associated symptoms (tinnitus, fullness of the ear,
histine was given in two of the treatment periods, and nausea, and vomiting) were also significantly
placebo during the other two periods. Twenty-two improved by betahistine, and the difference between
patients completed the trial. In total, they received betahistine and placebo was evident from the first
betahistine 32 mg daily, for a period of 4 months, and month of treatment. GISFaV scale, DARS, and
placebo also for the same length of time. Clinical DHI scores also show significant improvements
assessment of the investigator and daily symptom with betahistine in comparison to placebo. According
score cards filled by the patients were used to assess to the authors, both the physician’s judgment and the
evolution. patient’s opinion on the efficacy and acceptability of
 Betahistine in the treatment of peripheral vertigo 1209

95 patients with classic symptoms of unilateral

disabling Ménière’s disease were enrolled. Of these,
49 were randomized to betahistine 48 mg (16 mg
three-times daily) and 46 patients received acetazol-
amide 125 mg once-daily for 6 months.
A substantial benefit was observed in 51 of the
95 patients that could avoid surgery. A significantly
superior number of patients were in the betahistine
group than in the acetazolamide group [32 (65%) vs
19 (41%)]. The difference between groups was
significant (p < 0.05). Twelve patients in the betahis-
tine group and six in the acetazolamide group
Figure 1. Efficacy of betahistine in the treatment of peripheral eventually experienced a relapse and, thus, also
vertigo. After 3 months of therapy, betahistine significantly reduced underwent vestibular neurectomy.
the number of vertigo episodes. The mean number of monthly In the follow-up, with the purpose of facilitating
vertigo episodes was reduced from 6.7 (baseline) to 2.06 after vestibular compensation after surgery, 28 patients
3 months of treatment in patients with Ménière’s disease (MD),
received betahistine (48 mg daily; 16 mg three-
and from 6.9 to 1.91 monthly attacks in patients with paroxysmal
positional vertigo (PPV). Adapted from Mira et al. [15]. times/day) and 34 were treated with cinnarizine
(75 mg daily; 25 mg three-time/day) for 3 months.
Patients assigned to betahistine had a shorter period
the treatment were in agreement as to the superiority of disability and significantly better results on vestib-
of betahistine. Therefore, the outcomes of this study ular testing, which support a benefit of betahistine in
confirm the effective and safe profile of betahistine in facilitating vestibular compensation. Therefore, beta-
the treatment of Ménière’s disease and other types of histine seems to be the most effective medical option
peripheral vertigo [15]. to avoid vestibular neurectomy in patients with severe
Djelilovic-Vranic et al. [18] carried out a compar- Ménière’s disease and to facilitate post-operative
ative study of betahistine vs cinnarizine, with the goal compensation in patients that have undergone
of determining which drug is more effective in the vestibular neurectomy [19].
treatment of Ménière’s disease. Both drugs are Ganança et al. [20] from the Federal University of
histamine derivatives, but, while betahistine shows a São Paulo, Brazil, compare the efficacy and tolerabil-
weaker agonistic effect on histamine H1 receptors and ity between twice daily and three times daily betahis-
a stronger effect on histamine H3 receptors, cinnar- tine for Ménière’s disease.
izine seems to have a stronger effect on H1 receptors. In a randomized, open-label design, 120 consecu-
This study conducted at the Clinical Center of tive patients with well-established Ménière’s disease
Sarajevo University evaluated the effectiveness were assigned to betahistine 16 mg TID or 24 mg BID
of betahistine in 37 patients with the classic triad of for 24 weeks. Treatment efficacy was evaluated by
symptoms (episodic vertigo, fluctuating hearing loss, clinical outcomes in terms of severity, frequency, and
and tinnitus) of Ménière’s syndrome, and cinnarizine duration of vertigo episodes. Both betahistine
effect was evaluated in 36 patients with a less severe regimens demonstrated a significant improvement
clinical picture. Group with classic Ménière’s syn- (p < 0.01) in clinical outcomes from baseline to
drome was treated with 48 mg of betahistine daily and week 24. There was no significant difference between
was followed during 8 weeks, while the Cinnarizine dosage groups regarding efficacy at any time point
group received 150 mg daily and was also followed for during the study. The incidence of adverse events was
8 weeks. According to the authors, after just 1 month low in both groups, and the frequency of patients
of therapy better effects were noticed with betahistine reporting adverse events diminished with time.
in terms of symptoms reduction compared to the Therefore, the study of Ganança et al. [20] estab-
effects observed with cinnarizine [18]. lished that both oral regimens of betahistine 16 mg
A study of Colletti [19] compared the efficacy of TID and 24 mg BID provide comparable efficacy and
betahistine or acetazolamide in preventing the need tolerability for the treatment of vertigo in patients with
for vestibular neurectomy in patients with severe, Ménière’s disease.
incapacitating Ménière’s disease. The efficacy of A recent meta-analysis, conducted by Nauta [11],
medical treatments in facilitating post-operative assessed 12 double-blind, placebo-controlled, ran-
compensation of equilibrium after vestibular neurect- domized clinical studies that evaluated the efficacy
omy was also evaluated. In this trial conducted at the of betahistine in patients suffering from Ménière’s
ENT Department of the University of Verona, Italy, disease or vestibular vertigo. The clinical end-point
1210 R. Ramos Alcocer et al.

was the investigator’s overall opinion on the response frequency and dizziness and ameliorating the general
to treatment of vertigo symptoms, after at least 4 weeks condition of the patients [17].
of treatment. The cited meta-analysis of Nauta [11] evaluated
The randomized controlled trials included in the 12 double-blind, randomized, placebo-controlled clin-
meta-analysis were completed between 1966–2010. ical studies with betahistine in patients with vertigo from
The total daily dose of betahistine ranged from different origins. The odds ratios were all favorable to
16–48 mg, and treatment duration lasted from betahistine vs placebo and ranged from 3.37 (95%
14 days to 3 months. Using a random-effects model, CI = 2.14–5.29) to 2.23 (95% CI = 1.20–4.14) accord-
betahistine showed a statistically significant positive ing to different conditions. This meta-analysis demon-
effect on patients with vestibular vertigo or Ménière’s strated a significant benefit of betahistine on several
disease, compared with patients receiving placebo types of vertiginous syndromes [11].
(meta-analytical odds ratio [OR] = 2.58, 95% A meta-analysis has been carried out by Della
CI = 1.67–3.99). This means that, on average, the Pepa et al. [16] to assess the efficacy of betahistine
likelihood of a favorable outcome is almost 2-times in the treatment of vertiginous syndromes not related
higher for patients treated with betahistine than for to Ménière’s disease, such as positional paroxysmal
patients that received placebo. vertigo and vertigo secondary to arterial deficiency of
Sub-group analysis indicated also statistically sig- the vertebrobasilar area, regardless of the specific
nificant benefit with betahistine for each medical cause.
condition (vestibular vertigo or Ménière’s disease). Literature of clinical trials performed with betahis-
For Ménière’s disease, the meta-analytical OR was tine vs placebo in randomized double-blind, parallel-
3.37 (95% CI = 2.14–5.29), while, for vestibular group, or cross-over designs were reviewed. Selection
vertigo, the meta-analytical OR was 2.23 (95% of studies was limited to those that assessed betahis-
CI = 1.20–4.14). Therefore, the evidence supported tine compared to placebo in patients with vertiginous
the therapeutic benefit of betahistine for both symptoms not related to Ménière’s disease. Using
Ménière’s disease and vestibular vertigo [11]. the keywords established, 104 publications were
extracted from three global literature databases. Of
these studies, only seven were finally selected for the
Betahistine in BPPV and other vertiginous syndromes meta-analysis according to pre-established criteria.
Therefore, the meta-analysis was carried out on seven
A double-blind, randomized, controlled clinical trial double-blind, placebo-controlled randomized clinical
was conducted to assess the effects of betahistine in studies of betahistine vs placebo.
addition to Epley maneuver on the quality-of-life of The overall case series obtained from the seven
patients with benign BPPV. In this study carried out studies selected comprised a total of 367 patients.
by Guneri and Kustutan [17], 72 patients (45 female A preliminary analysis of the studies taken into
and 27 male) were enrolled and assigned to three account for the meta-analysis revealed that typically
different therapeutic schemes. The first group was daily doses of betahistine vary from 32–48 mg,
treated with Epley maneuver only. The second group and duration of treatment periods ranged from
received placebo twice daily for 1 week in addition to 1–3 months. The results of the meta-analysis support
Epley maneuver, and the third group received beta- the therapeutic benefit of betahistine vs placebo. The
histine 48 mg/day (oral doses of 24 mg twice daily) for overall sample shows an odds ratio of 3.52 (95%
1 week in addition to Epley maneuver. Effectiveness confidence interval = 2.40–5.18) and a relative risk
and safety was evaluated in each group, as well as of 1.78 (95% confidence interval = 1.48–2.13) in favor
between them, by means of four different scales for of betahistine. In conclusion, the meta-analysis con-
vertigo and associated symptoms (Dizziness Handi- ducted by Della Pepa et al. [16] confirms the benefit
cap Inventory, Vestibular Disorders Activities of Daily of betahistine for the treatment of different vertiginous
Living Scale, European Evaluation of Vertigo, and syndromes not related to Ménière’s disease.
Vertigo Symptom Scale) [17].
Epley maneuver, alone or combined with betahis- Conclusion
tine or placebo, was very effective and showed a high
success rate (86.2%). However, betahistine in The most common causes of vertigo are peripheral
addition to Epley maneuver was more effective than vestibular disorders. The treatment of vertigo requires
Epley maneuver alone or combined with placebo for an integral and multi-modal approach, and it usually
the control of vertiginous symptoms (p < 0.05). Beta- includes the use of medication, physical therapy, and
histine also improves the quality-of-life of patients lifestyle adaptations. The etiology and physiopathology
with peripheral vestibular vertigo by decreasing attack of Ménière’s disease, BPPV, and other types of
 Betahistine in the treatment of peripheral vertigo 1211

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Declaration of interest: Editorial assistance was
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