Dimenhydrinate

Cinnarizine/dimenhydrinate for vertigo

Diphenhydramine, dimenhydrinate: misuse

Meniere's disease

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.

Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial

Background and objective: Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert^?) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo.
Methods: In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments.
Results: Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients.
Conclusion: The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders.
Study registration: EudraCT No. 2011-004025-27.

Misuse and dependence of dimenhydrinate: A mixed studies systematic review

Background: Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been reports of potential DMH tolerance and dependence and a possible euphoric potential accompanying heavy use (>100 mg/day). Despite the potential for misuse, there is a gap in the literature concerning patterns, characteristics, and potential mechanisms of DMH misuse.
Aims: This review aimed to synthesize evidence on the pharmacology, clinical effects, and management of DMH misuse and dependence to inform clinical decision making and relevant drug policy.
Methods: We conducted a systematic review in accordance with the PRISMA guidelines and using Cochrane collaboration methods. We searched seven databases from their inception through July 2019. To be included in the review, studies needed to measure or focus on one or more dimensions of morbidity or mortality related to the misuse of DMH. Quantitative, qualitative and mixed-method studies were included in order to capture the breadth of possible studies. Studies were excluded if they did not fit into the conceptual framework of the study of if they focused primarily on the misuse of other substances. A narrative synthesis of study findings was pursued given the limited capacity for a quantitative meta-analysis.
Findings: We identified 24 studies, which described a range of neuropsychiatric sequelae related to DMH consumption, including seizures, psychosis, depression, intoxication (resembling anticholinergic syndrome) and withdrawal. The sedative and euphoric properties, readily available nature, and low cost of DMH appear to facilitate DMH dependence, which were more commonly reported among individuals who had concurrent psychiatric disorders, displaying symptoms such as low motivation, poor concentration, and delirium. The overall quality of studies identified by this review was low-largely because the majority of studies were case reports or review articles, with few intervention or cohort studies.
Conclusions: There is some evidence to suggest the existence of DMH-related syndromes involving intoxication, withdrawal, and dependence, more commonly among long-term, heavy DMH consumers. However, higher quality studies are needed to confirm preliminary findings that there may be a biological basis for such syndromes.