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17.06.2015
Vestibular vertigo is a primary symptom in neurootological clinical practice and is common among cerebrovascular diseases.
The complicated perception of body position and its separate parts in space is a result of analyzed and synthesized impulses by the vestibular analyzer, by both superficial and deep proprioception, and by the ocular analyzer. The aim of our investigation was to evaluate the effect of treatment with 8 mg and 16 mg of Betaserc on patients (workers in the transport system) with vascular auditory and vestibular disturbances. A detailed neurootological history was obtained by means of a questionnaire, and otological and neurological examinations were conducted in each patient.
First, with the help of Frenzel's spectacles, we evaluated spontaneous reactions, checking for spontaneous, positional, and latent nystagmus. Figure 2 shows a decrease in complaints of vertigo (16 patients) and dizziness (14 patients) on the twentieth day in one-half of the 30 patients treated with 16 mg of Betaserc.
The frequency of attacks was lower in both treated groups, but the result was considerably better after treatment with 16 mg of Betaserc. Regarding nystagmus reactions, the general test showed the presence of different nystagmus forms-horizontal, horizontal rotatory, and rotatory-according to the phase and nosological units. On the twentieth day of treatment with 16 mg of Betaserc, we noted an improvement in the spontaneous and, especially, the latent nystagmus symptoms. We confirmed the opinion of many scientists that a larger amount of Betaserc leads more rapidly to considerable acceleration of the vestibular function recovery processes [8,9]. Complete investigation revealed decreased complaints of vertigo and dizziness (in frequency and strength of attacks) among one-half of our patients on the twentieth day of treatment with 16 mg of Betaserc.
On the basis of investigations carried out, we recommend 16 mg of Betaserc three times daily in the acute phase. SoundCure ® Quote “For the tinnitus patient, living with this persistent condition requires changing the way he or she thinks about health care and daily life. In a randomized, double-blind clinical study, we evaluated the efficacy and tolerability of the fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg (Arlevert [ARL]) in comparison to betahistine dimesylate (12 mg) in 82 patients suffering from Meniere's disease for at least 3 months and showing the characteristic triad of symptoms (paroxysmal vertigo attacks, cochlear hearing loss, and tinnitus). Meniere's disease, described for the first time in 1861 by Prosper Meniere, is characterized by a triad of symptoms in a characteristic, classic pattern of episodic vertigo, tinnitus, and fluctuating sensory hearing loss [1-3]. Surgical treatment of Meniere's disease is indicated only in severe cases and after attempts of conservative therapy have failed. The antivertiginous drug Arlevert (ARL), a fixed combination of the calcium antagonist cinnarizine (20 mg per tablet) and the antihistamine dimenhydrinate (40 mg per tablet), has been successfully used for a long time in the treatment of vertigo of various origins and has been tried and tested in numerous randomized, double-blind clinical trials [6,10,11]. Cinnarizine primarily leads to a cerebral and cochlear increase of perfusion [13,14] and acts as a vestibular sedative through inhibition of the calcium influx into the vestibular sensory cells [15].
In our study, the efficacy and safety of the fixed combination of cinnarizine and dimenhydrinate was investigated in patients suffering from Meniere's disease.
The patient population consisted of 82 male and female white outpatients (age > 30 years) suffering from Meniere's disease for at least 3 months. Patients taking benzodiazepines, acetylsalicylic acid, or piracetam were eligible for enrollment. The study was carried out according to a randomized, double-blind, reference-controlled design with two parallel groups. The patients were asked to judge the intensity of vertigo and concomitant symptoms on a visual analog scale with possible ratings between 0 (no symptom) and 4 (very strong symptom).
Concomitant symptoms of vertigo (assessed by visual analog scale), vestibulospinal tests (assessed by CCG), ENG tests, and audiometry and a global judgment by both patient and investigator were used as secondary criteria of efficacy.
Vestibulospinal (Unterberger's and Romberg's) tests were registered by CCG [16, 17], as previously described [10,18].
The safety of the study medications was assessed by registration of adverse events on the occasion of each follow-up visit; in addition, systolic and diastolic blood pressure was measured at each visit. Statistical analysis was performed on the basis of the per-protocol population, including all patients who completed the study without any protocol deviation (n = 80). Comparability of demographic and anamnestic variables between treatment groups before the start of treatment was assessed at the 20% significance level using the Wilcoxon-Mann-Whitney test (U-test) in case of quantitative data and Fisher's exact test in case of categorical data, as appropriate.
Eighty-two patients were randomly assigned to treatment and were valid for safety analysis. The patients in the two treatment groups were comparable with regard to demographic characteristics (Table 1). Tinnitus, typically associated with Meniere's disease, showed a relatively high initial mean score of approximately 3.3 in both treatment groups (Fig. The score of the mean vegetative symptoms, including nausea, vomiting, sweating, and tachycardia, also markedly improved during the treatment, with statistical significance reached as early as at the end of the first week of therapy (see Fig. Spontaneous nystagmus was displayed by three patients in the ARL group and two patients in the betahistine group before the start of treatment. In pure-tone audiometry, patients with unilateral disease showed an initial mean hearing loss on the side of the affected ear of approximately 40 dB, which was significantly reduced in the course of the 12-week treatment in patients belonging to the ARL group (p =.042) but not in patients belonging to the betahistine group.
Finally, the global assessments of efficacy by both the investigator (data not shown) and the patients were largely in line with the distinct improvements of the SM and associated symptoms in the course of therapy. After 1 week of therapy, more than 90% of the patients judged the tolerability of the study medication as very good. The results of our study demonstrate a high antivertiginous efficacy and good tolerability of the fixed combination of cinnarizine and dimenhydrinate in the treatment of patients with Meniere's disease.
All parameters of the vestibulospinal tests (recorded by CCO) distinctly improved during the course of therapy (see Table 3), with comparable results for both medications. Spontaneous or positional nystagmus was found in fewer than 10% of the patients, which parallels clinical experience. In contrast to the patients' subjective assessment of hearing, pure-tone audiometry did not show a clear-cut recovery of cochlear function during the treatment (Table 5). The good antivertiginous efficacy of the combination preparation found in our study corresponds with the findings of previous clinical studies in patients suffering from vertigo of various origins [9,10], from which patients with Meniere's disease had been excluded. The high efficacy of the two medications may be explained by their pharmacodynamic properties. The tolerability of both medications was judged by the vast majority of the patients (97.5%) as very good, which is underlined by a very low rate of dropouts (two patients in the betahistine group) and an absence of adverse events in any of the 80 patients who completed the study. In conclusion, the fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg, proved to be safe and highly effective in the treatment of Meniere's disease. The aim of this investigation was to evaluate the effect of betahistine dihydrochloride (Betaserc), 8 and 16 mg, on patients who were transport system workers with vascular auditory and vestibular disturbances. Vestibular receptors play a main role in this complex system and determine changes both in linear and angular acceleration and in gravity strength [1-3]. Arterial hypertonia or atherosclerosis is accepted to be the most common etiopathogenic factor. The patients, all transport workers, presented with vascular pathology of the vestibular and auditory analyzer.
Tonal threshold audiometry was performed using a Siemens (Copenhagen, Denmark) SD-50 audiometer. The total number of patients treated with 16 mg of Betaserc was 30 (18 with central otoneurological syndrome and 12 with peripheral otoneurological syndrome). On day 45, substantial improvement was seen among one-third of the 20 patients treated with 8 mg of Betaserc.
The otological and neurological status of all patients was normal before starting treatment. Figure 3 shows the breakdown of patients according to whether they experienced spontaneous, latent, or positional nystagmus (according to Frenzy's spectacles) and to whether they were being treated with 8 mg or 16 mg of Betaserc.
Subdivision of men with spontaneous (SNy), latent (LNy), and positional nystagmus (PNy) (according to Frenzel's spectacles) during treatment with 8 mg and 16 mg of Betaserc. Better results were received after treatment with 16 mg of Betaserc, considering spontaneous and, especially, latent nystagmus symptoms.
The medication is very well tolerated, has no sedative effect, and is suitable for long-term treatment of transport workers with auditory and vestibular disturbances of vascular etiology.
Remind patients that tinnitus is different for every individual and that there is much we are still learning about tinnitus. Fixed Combination of Cinnarizine and Dimenhydrinate Versus Betahistine Dimesylate in the Treatment of Meniere's Disease: A Randomized, Double-Blind, Parallel Group Clinical Study.
The treatment (one tablet three times daily) extended to 12 weeks, with control visits at 1,3,6, and 12 weeks after drug intake.
Frequently associated symptoms are aural fullness and vegetative symptoms, such as nausea and vomiting.
Medical treatment is composed of a great variety of agents, including vasodilators and vestibular suppressants [5,6].


The combination preparation is highly effective in both central and peripheral vestibular disorders owing to its dual mechanism of action.
Dimenhydrinate acts as an antihistamine with anticholinergic properties and exhibits ani vertiginous and antiemetic effects. Betahistine was chosen as the reference drug, as it is a generally accepted standard treatment, especially in the prophylactic treatment of Meniere's disease.
Antivertiginous and or cerebrovascularly active drugs had to be discontinued prior to the start of treatment (1-week washout phase). It was conducted in accordance with the Declaration of Helsinki and the guidelines for good clinical practice. From the ratings for six vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, and blackout) and six vertigo trigger factors (change of position, bowing, getting up, driving by car or train, head movements, and eye movements), a mean vertigo score (SM) was calculated, with theoretical values between 0 (no symptom at all) and 4 (all 12 symptoms present with maximum intensity). Concomitant vegetative symptoms (nausea, vomiting, sweating, and tachycardia) and further symptoms related to the disease (tinnitus, impaired hearing, aural fullness, headache, and impaired vision) were registered.
The intent-to-treat analysis included data of only 1 additional patient (n = 81) and is therefore not considered further. Analysis of primary and secondary efficacy variables was based on changes from baseline, as evaluated at 1,3,6, and 12 weeks after the start of treatment, with special consideration of the SM as a global parameter for vertigo intensity. Categorical (efficacy and safety) variables were descriptively compared by means of Fisher's exact test. One patient of the betahistine group did not return to any subsequent control visit (owing to an adverse event) and was not valid for the intent-to-treat analysis.
The study population included 39 male and 43 female patients, with a mean age of approximately 50 years in both groups. Vertigo symptoms (mean score [SM]) in the course of a 12-week treatment with the fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg (ARL) or betahistine dimesylate, 12 mg, in Meniere's disease. Tinnitus (mean score) in the course of a 12-week treatment with a fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg (ARL) or betahistine dimesylate, 12 mg, in Meniere's disease. All six test parameters improved highly significantly in the course of the 12-week treatment, with mean reductions of approximately 40-60%. Only one patient (in the ARL group) still presented spontaneous nystagmus after the 12-week treatment period.
Nystagmus frequencies and amplitudes were mostly within the normal range before, during, and after treatment. Hearing loss on the non affected side was initially approximately 13 dB in patients in both groups and remained largely unaffected by either treatment. After 1 week of treatment, more than one-half of the patients in each group stated an overall improvement in their health condition. Only one patient (in the betahistine group) reported a nonserious adverse event (neurotic symptoms, judged by the investigator as not being related to the study medication), which was the reason for the retreat within the first week of the study (dropout). Of the remaining patients, three of the betahistine group and four of the ARL group rated the tolerability as good, and only one patient in each group gave the rating of moderate. Because severe vertigo sensations are usually the most distressing complaint of patients suffering from Meniere's disease, a vertigo score, SM (mean score of vertigo symptoms and trigger factors), was chosen as the primary efficacy variable. Vegetative symptoms (mean score [VM]) in the course of a 12-week treatment with a fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg (ARL) or betahistine dimesylate, 12 mg, in Meniere's disease. The majority of the Meniere's patients show spontaneous or provoked nystagmus during or immediately after the vertigo attacks but rarely during the period of remission [17].
Hearing loss in Meniere's disease is sensory, and it characteristically displays a fluctuating but progressively worsening course, with little or no correlation to vestibular dysfunction [23,24]. In patients with otogenic vertigo, acute vestibular disorders, and vertigo due to vertebrobasilar insufficiency, the fixed combination of cinnarizine and dimenhydrinate proved to be significantly more effective than was betahistine [10], whereas in Meniere's disease, our study demonstrates a very similar efficacy but no statistically significant difference between the two treatments. From a pathogenetic point of view, Meniere's disease is the classic form of endolymphatic hydrops [24]. This unusually low incidence of adverse events may reflect a generally positive attitude of the patients toward the study medication owing to the subjectively experienced success of the treatment, which may have prompted the patients to overlook minor inconveniences or adverse reactions.
Owing to its pharmacological properties, the combination preparation may be used in both the management of acute episodes and in long-term therapy. We examined 50 patients, 30 of whom were treated with 16-mg doses and 20 of whom received 8-mg doses of Betaserc. Pathological changes in functioning of the aforementioned systems cause vertigo [4], dizziness, a sensation of floating, noise in the ears, and balance disorders. Sensory structures, being highly differential, are more vulnerable to ischemia than are other nerve structures [5,6]. In the central ear, it improves histaminergic neurotransmission by blocking presynapsis H3 receptors, it increases histamine release in synapses, and it normalizes the exciting processes in vestibular nuclei of the medulla oblongata [7].
The otoneurological investigation was conducted before and on the twentieth and the forty-fifth days of treatment in the Department of Neurology and Neurootology of the National Multiprofile Transport Hospital, King Boris III, Sofia. Examination of the vestibular system was directed at both spontaneous and provoked reactions.
The total number of patients treated with 8 mg of Betaserc was 20 (12 with central otoneurological syndrome and 8 with peripheral otoneurological syndrome). Complaints of vertigo remained in 6.7% of the 16 vertigo patients receiving 16 mg of Betaserc, as compared to 20% of the 11 vertigo patients treated with 8 mg of Betaserc.
No pathological change was found after tonal audiometry; the results were within normal limits (hearing decrease of 5-10 dB, mainly for the high-frequency zone) for those older than 36 years. On the twentieth day after treatment, the percentage of patients with values of less than 1.50 (within normal limits) was increased by 40% (12 patients) in those treated with 16 mg of Betaserc and by 20% (4 patients) when treated with 8 mg of Betaserc. Also, the symmetry of reaction was considerably improved after above-threshold provocation, mainly in terms of duration, slow-phase speed, and amplitude. The study demonstrated for both the fixed-combination ARL and for betahistine a highly efficient reduction of vertigo symptoms in the course of the 12 weeks of treatment; however, no statistically significant difference between the two treatment groups could be established. The vertigo attacks (predominantly rotational vertigo) occur suddenly without warning-albeit in a majority these are preceded by an "aura," as in epilepsy, with aural fullness, tinnitus, and nausea for 10-30 minutesand last for several minutes to hours; they recur after days, weeks, or months, followed by episodes with weak or no symptoms (remission).
Owing to these pharmacological properties of the components, the fixed combination is expected to show a favorable effect in the treatment of Meniere's disease:cinnarizine, with a prophylactic effect by means of improvement of inner ear circulation, and dimenhydrinate, intended to alleviate acute vertigo attacks through its anti vertiginous, antiemetic, and sedati ve effects.
Exclusion criteria were convulsive seizures, suspicion of compressive intracranial processes, narrow-angle glaucoma, prostate adenoma with residual urine, Parkinson's disease, asthma, gastrointestinal ulcer, acute poisoning, severe renal insufficiency, epilepsy, and alcohol abuse.
The study documents were reviewed and approved by an independent ethics committee and by competent health authorities. For randomization, a computer-generated block sequence was used, which ensured equal distribution of the patients into the two treatment groups. The change of SM in the course of the 12 weeks of treatment was used as the primary efficacy criterion. The change of SM in the course of the 12-week treatment phase was used as the primary criterion of efficacy.
Analysis of changes from baseline within a treatment group was done by the Wilcoxon signed rank test. One other patient of the betahistine group discontinued the study after the second intermediate examination (week 3) for unknown reasons.
The mean decreases in SM in each therapy group were highly significant at all times of assessment (p p > .05 , Mann-Whitney U-test) . The mean reductions in the subjective scores in each therapy group were highly significant at all times of assessment (p p > .05, Mann-Whitney U-test). In both groups, the vegetative symptoms had nearly completely subsided by the end of the 12-week treatment period. In particular, the parameter of lateral sway (Unterberger's test) in the ARL group decreased to a significantly greater extent during the 12-week treatment period as compared to the symptom in the betahistine group (p =.042). Caloric weakness and directional preponderance did not change significantly under either treatment. In patients with bilateral disease, the hearing loss was initially approximately 44 dB in either group and showed no significant changes in the course of therapy.
After 12 weeks of therapy, all patients judged the tolerability of the two medications as very good, except for one patient in each group, who gave the rating of good.
Both the fixed combination and betahistine led to a highly significant reduction of SM by more than 80% in the course of the 12-week therapy (see Fig.
Scores for the symptoms of nausea, vomiting, sweating, and tachycardia were averaged to a mean vegetative score per patient.
The reduction of this parameter seems to reflect a normalization of a patient's condition, at least with respect to the balance system, and corresponds with the reduction of the SM, chosen as the primary criterion of efficacy. Caloric responses are reduced in approximately 40-70% of the cases [2,17]; the excitability decreases more rapidly at the beginning of the disease and stabilizes in the following 10 years to one-half or one-third of the initial level [2,22].


The initial hearing loss of 40-45 dB at the affected ear is close to values found in the chronic phase of the disease [22,23,25] and compatible with the long mean duration of the disease (6 years) in the patient population of our study. Several vasodilators have been used for the treatment of Meniere's disease, on the basis of the hypothesis that ischemia of the stria vascularis plays an important role in the development of endolymphatic hydrops [4].
Efficacy and safety were found to be similar to the widely used standard therapy with betahistine.
Efficacy and tolerability of a fixed combination of cinnarizine and dimenhydrinate in treatment of vertigo. Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: A search for the locus of their anti motion sickness action. The main symptom in neurootological clinical practice - vestibular vertigo - is common among disturbances of cerebral hemodynamics and the blood supply of peripheral and stem parts of the vestibular analyzer. During the investigation, patients were given either only 16 mg of Betaserc three times daily or 8 mg of Betaserc three times daily, as those with arterial hypertonia underwent simultaneous antihypertensive treatment.
Vertigo and dizziness were the main symptoms of patients with otoneurological disease, and the symptoms often were accompanied by noise in the ears, hearing decrease, and balance disorders. Complaints of dizziness remained in 10% of the 14 dizziness patients treated with 16 mg of Betaserc, as compared to 25% of the 9 dizziness patients treated with 8 mg of Betaserc. These data correlate with the results of above-threshold provocation, objectified by electronystagmography (Fig.
As compared to static body changes, better results were registered in kinetic changes on the twentieth day of treatment with 16 mg of Betaserc.
Arterial pressure was not influenced during treatment with either 8 mg or 16 mg of Betaserc.
Results of coordinating and statokinetic tests were also improved after treatment of patients with 16 mg of Betaserc, as better results were achieved in body kinetic indices. Similar results were found for tinnitus (approximately 60% reduction) and for the associated vegetative symptoms (almost complete disappearance).
The complete clinical picture usually develops only after several years, which makes it more difficult to establish the diagnosis in earlier stages.
Conversely, vestibular suppressants, such as dimenhydrinate, have proven to be very effective in the management of acute Meniere's attacks owing to their anti vertiginous, antiemetic, and sedative properties [5,6,9]. Further exclusion criteria included suspected acoustic neurinoma, apparent infection of the inner ear, caloric inexcitability (areflexia), vertigo due to unsolved organic primary disease, previous surgical treatment for Meniere's disease, and benign paroxysmal positional vertigo. The entry examination took place on day 1 (before drug intake), followed by three intermediate examinations after 1, 3, and 6 weeks and a final examination after 12 weeks. The caloric test with ENG registration was performed according to standard procedures (irrigation of 20 ml water at 30° and 44°C for 30 seconds) [18]. All other patients (n = 80) completed the study with no protocol violations and were therefore valid for the per-protocol analysis. On average, the enrolled patients suffered for 6-7 years (5 months-29 years) from Meniere's disease, the manifestation being approximately 65% unilateral and 35% bilateral, which is in accord with data found in the literature [20]. The statistical analysis showed highly significant changes within each group from the first week (p between the two treatment groups at any time. The other parameters showed no significant difference between the two treatments (Table 3). In patients with unilateral disease, the affected ear showed a lower excitability than did the nonaffected ear. No statistically significant difference between the two treatment groups could be observed in any case. Blood pressure, measured at each examination visit, showed no changes of clinical relevance during the study. The mean decreases in VM in each therapy group were highly significant at all times of assessment (p p > .05, Mann-Whitney U-test). Furthermore, the fixed combination was found to reduce the parameter of "lateral sway" in the Unterberger test, in a significantly stronger way than did betahistine, which may be attributed mainly to the centrally active component, dimenhydrinate, of the combination preparation. In accordance with literature data [4], in the unilateral cases, the mean frequency at the affected side was approximately 30% lower than that at the non affected side and close to the lower limit of the normal range. Audiometry showed a slight but statistically significant recovery only in unilateral cases after 12 weeks of therapy with the combination preparation.
Betahistine is known to cause vasodilatation and improvement of cochlear blood flow [26] through a complex interaction with histamine receptors (stimulation of HI-receptors and inhibition of presynaptic H3-receptors) [27]. This finding led us to use the medicine Betaserc (betahistine dihydrochloride), which has both peripheral and central effects and brings to normal the imbalance in the vestibular system. The results of the respective treatment of patients with balance disorders, hearing decrease, and noise in the ears are nearly identical. Vestibulospinal reactions, recorded by means of craniocorpography, also improved distinctly, with a statistically significant superiority of ARL versus betahistine (p p =.042) was found for the combination preparation after 12 weeks of treatment. Pregnant women and nursing mothers and women of child-bearing potential who were not taking adequate contraceptive measures were not allowed to participate in the study.
On the occasion of all visits, vertigo anamnesis tests (including concomitant symptoms), vestibulospinal tests (Unterberger's and Romberg's tests) registered by craniocorpography (CCG), registration of spontaneous positional nystagmus (Frenzel's glasses), and pure-tone audiometry were carried out.
Nystagmus frequency-which served for calculation of caloric weakness and directional preponderance, according to Jongkees [19] -as well as amplitude and culmination area were determined. The vast majority of the patients (78 of 82) had been pretreated with antivertiginous drugs, some with betahistine (38 patients), cinnarizine (6 patients), and the combination preparation (4 patients). The marked improvements in subjective judgment of hearing reported by both groups of patients during therapy might be attributed to a subjective increase in stimuli perception or processing within the context of general recovery. The therapeutic efficacy of the fixed combination results from the different effects of its two active substances, cinnarizine and dimenhydrinate. On the basis of the investigations carried out, we recommend 16 mg Betaserc three times daily in the acute phase. Considering the duration, slow-phase speed, amplitude, and organization of nystagmus, symmetry of reaction is considerably improved after above-threshold provocation and 45 days treatment with 16 mg of Betaserc. The tolerability was judged by the vast majority of patients (97.5%) in both groups to be very good. Concomitant medications, such as aminoglycoside antibiotics, monoamine oxidase inhibitors, tricyclic antidepressants, parasympatholytics, glucocorticoids, and heparin were not permitted. In addition, that caloric nystagmus test (e1ectronystagmography [ENG]) was performed at day 1 and after 3 and 12 weeks oftreatrnent. Standard pure-tone threshold audiometry was performed at frequencies of 250, 500,1,000, and 2,000 Hz. 2), hearing loss, and aural fullness (see Table 2) and for the associated vegetative symptoms (Fig. The calcium antagonist cinnarizine leads to vasodilatation and improves circulation in compromised intra-and extracranial areas [14,28]. The medication is very well tolerated, has no sedative effect and is suitable for long-term treatment.
Only one patient (betahistine group) reported a nonserious adverse event, and two betahistine patients did not complete the study.
Both patients and investigator gave a global judgment of the efficacy and tolerability of the study medication after 1,3,6, and 12 weeks of treatment. Furthermore, cinnarizine shows labyrinth sedative properties [28] and has therefore proven efficacy in the management of vertigo episodes of various origins, including also the acute phase of Meniere's disease. In conclusion, the combination preparation proved to be a highly efficient and safe treatment option for Meniere's disease and may be used both in the management of acute episodes and in long-term treatment. Compliance was controlled on the basis of the number of tablets returned by the patients at the end of treatment. Nearly one-third of the patients had concomitant diseases, most frequently hypertension, and antihypertensives were the most frequent concomitant medication.
The actions of cinnarizine are reinforced by those of dimenhydrinate, which acts predominantly centrally. Dimenhydrinate exerts a regulating effect on the vestibular nuclei and closely associated vegetative centers in the brainstem [29,30].
Owing to its antivertiginous and antiemetic properties, dimenhydrinate is particularly effective in the treatment of vertigo and associated vegetative symptoms, and it is also recommended for the management of acute episodes in Meniere's disease [4,31].



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