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Otolaryngology–Head and Neck Surgery 154(5)

results, while the remainder demonstrated no or inconclu- sive hearing results ( Table 4 ). Fifteen (79.0%) studies reported improvement in vertigo symptoms, with 2 (10.5%) reporting mixed results and 2 (10.5%) reporting no vertigo outcomes ( Table 5 ). Ten (52.6%) studies reported no side effects as a result of therapy. Three (15.8%) studies specifi- cally reported abdominal discomfort, and the remainder reported different constellations of side effects ( Table 6 ). Discussion MD is a common condition with occasionally debilitating symptoms. As the pathophysiology is not well understood, devising effective therapeutic strategies has been a challen- ging task. Acute symptom exacerbations can be treated with benzodiazepine and steroid regimens. Physicians may offer more invasive procedures for refractory cases, including medi- cal labyrinthectomy with transtympanic gentamicin injections, endolymphatic sac decompression, surgical labyrinthectomy, and surgical vestibular nerve section. Combinations of low-salt diet restriction and oral diuretics have largely been used as maintenance therapy. Despite the use of diuretics for MD, lit- erature reviews have consistently demonstrated lack of evi- dence of effectiveness. The Cochrane Group published a thorough systematic review of diuretic efficacy in MD patients in 2006 and an update in 2010; however, no RCTs met their rigorous standards for a systematic review. 5 We realized an opportunity to broaden inclusion criteria to all study designs beyond RCTs to evaluate the potential benefits of diuretic therapy. We found 19 studies of Level of Evidence 4 or higher, per the Oxford Centre for Evidence-Based Medicine, with considerable heterogeneity in patient population, study design, diuretic type and dosage, follow-up time, and out- comes. Level of Evidence 4 includes studies that are either case series or poor-quality cohort and case-control studies. This heterogeneity precluded formal meta-analysis. Only 4 RCTs were included in our review. 8-11 One RCT directly compared hydrochlorothiazide with betahistine with no pla- cebo arm, and both were found to improve vertigo. 10 Betahistine does not have known diuretic properties but was included, as it was a treatment arm in comparison with hydrochlorothiazide. One RCT with a placebo arm investi- gated Dyazide (hydrochlorothiazide and triamterene) and found significant improvements in vestibular symptoms but not in hearing or tinnitus. 11 Another RCT with a placebo arm investigated hydrochlorothiazide and found statistically significant improvements in both hearing loss and vestibular symptoms but no significant improvement in tinnitus. 8 Last, a low-quality RCT compared isosorbide with 2 control compounds—methyl acid dihydroergotoxine and vitamin B3—and found significant improvements in headache and tinnitus. 9 The remainder of the studies were retrospective case series, 12-23 case-control studies, 24,25 and 1 prospective case series. 26 As the studies analyzed are of mostly ‘‘low’’ quality with heterogeneous methods for reporting outcomes, caution must be exercised in drawing conclusions from the

Figure 1. PRISMA-P 7 flow diagram for evaluation of identified studies.

grading system, 13 (68.4%) were classified as level 4; 2 (10.5%), level 1a; 2 (10.5%), level 3b; and 2 (10.5%), level 2b. The most common study country of origin was Japan (n = 6, 31.6%), followed by Sweden (4, 21.1%), and 1 each (5.3%) of England, Germany, Hungary, Italy, Mexico, Netherlands, South Korea, Turkey, and the United States. The diagnostic and reporting criteria varied. The most common criteria set used was the American Academy of Otolaryngology—Head and Neck Surgery Committee on Hearing and Equilibrium guidelines (n = 4), followed by the 1972 American Academy of Ophthalmology and Otolaryngology criteria (n = 3) and the Japan Society for Equilibrium Research for MD guidelines (n = 3). The remainder reported a constellation of symptoms and various diagnostic tests as inclusion criteria for MD. Eight medications with diuretic properties were analyzed. Six (31.6%) studies investigated isosorbide, 5 (26.3%) hydro- chlorothiazide, 2 (10.5%) acetazolamide, 2 (10.5%) chlorthali- done, and 1 (5.3%) each of betahistine or hydrochlorothiazide, chlorthalidone-acetazolamide, hydrochlorothiazide-triamterene, and nimodipine. Betahistine does not have known diuretic properties but was included, as it was a treatment arm in a study investigating hydrochlorothiazide. The dosing, therapy duration, and follow-up period varied widely ( Table 2 ). The outcome measurements varied from unstructured reports of symptomology, ancillary testing (electrocochleography, gly- cerol tests, vestibular testing), and audiology variables to formal reporting of accepted guidelines, including the 1985 Academy of Otolaryngology—Head and Neck Surgery Committee on Hearing and Equilibrium guidelines, 1972 American Academy of Ophthalmology and Otolaryngology standards, and the Japan Society for Equilibrium Research for MD guidelines ( Table 3 ). Eight studies (42.1%) reported a degree of objective hearing improvement. Six (31.6%) reported mixed hearing

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