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The natural history of MD is highly variable, which can
make it difficult to discern differences between treatment
and therapeutic effects. The natural history of an individual
patient would be difficult to take into account when analyz-
ing data from interventions, but this factor may explain the
variation seen in the outcomes reported in the studies we
reviewed. Moreover, we cannot ascertain the percentage of
patients who experience spontaneous symptom improvement
without the use of diuretic therapy. The natural history of
MD lends itself to spontaneous recovery from symptoms
without any intervention. Only 2 of our sources were RCTs
in design with a placebo as control.
8,11
Patients in these pla-
cebo groups did experience symptom improvement,
although this was not significant in either RCT. Last, we
suspect that publication bias may also explain the relative
frequency of positive results reported by the compiled stud-
ies in this review. It is probable that studies with negative
results either have not been submitted or were not accepted
for publication.
Conclusion
Multiple low-evidence-level studies report that oral diuretic
therapy may be beneficial in the medical management of MD.
If feasible, placebo-controlled studies will be required to fur-
ther substantiate these claims. Improvement in vertigo episode
frequency was often reported, with less convincing evidence
for improvement in hearing outcomes. These conclusions are
mitigated by multiple limitations, including the natural history
of MD, study design, and the possibility of publication bias.
Further investigation of the pathophysiology of MD will be
essential for providing tailored direction for established and
new therapies. Attention will need to be paid to the natural his-
tory of MD to determine true treatment effects.
Acknowledgments
We thank the Canadian Medical Association reference librarians
for their assistance in constructing the MEDLINE literature review
algorithm.
Author Contributions
Matthew G. Crowson
, project design, data collection, data analy-
sis, manuscript preparation, drafting, final approval, accountability
for all aspects of the work;
Aniruddha Patki
, Project design, Data
analysis, drafting, final approval, accountability for all aspects of
the work;
Debara L. Tucci
, Project design, drafting, final
approval, accountability for all aspects of the work
Disclosures
Competing interests:
Debara L. Tucci, consult for Otonomy
(chair, Data and Safety Monitoring Board).
Sponsorships:
None.
Funding source:
None.
References
1. Harris JP, Alexander TH. Current-day prevalence of Meniere’s
syndrome.
Audiol Neurootol
. 2010;15:318-322.
2. American Academy of Otolaryngology—Head and Neck
Foundation. Committee on Hearing and Equilibrium guidelines
for the diagnosis and evaluation of therapy in Meniere’s dis-
ease.
Otolaryngol Head Neck Surg
. 1995;113:181-185.
3. Gibson WP. Hypothetical mechanism for vertigo in Meniere’s
disease.
Otolaryngol Clin North Am
. 2010;43:1019-1027.
Table 7.
Mechanisms of Action for Selected Diuretic Agents.
a
Agent
Mechanism of Action
Acetazolamide
Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion
secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and
water. Decreases production of aqueous humor and inhibits carbonic anhydrase in the central
nervous system to retard abnormal and excessive discharge from its neurons.
Chlorthalidone
Sulfonamide-derived diuretic that inhibits sodium and chloride reabsorption in the cortical-diluting
segment of the ascending loop of Henle.
Hydrochlorothiazide
Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as
well as potassium and hydrogen ions.
Isosorbide
Osmotic diuretic with properties similar to those of mannitol.
Nimodipine
Nimodipine is a dihydropyridine calcium channel blocker that has the general properties of
nifedipine, which includes vasodilatation, with reduced peripheral resistance, blood pressure, and
afterload; increased coronary blood flow; and a reflex increase in heart rate. Additional evidence
suggests a diuretic action of calcium channel blockers through interference with renal and
extrarenal systems involved in the regulation of physiologic fluid and electrolyte balance.
35
Triamterene
Blocks epithelial sodium channels in the late distal convoluted tubule and collecting duct, which
inhibits sodium reabsorption from the lumen. This effectively reduces intracellular sodium,
decreasing the function of Na
1
/K
1
ATPase, leading to potassium retention and decreased calcium,
magnesium, and hydrogen excretion.
a
Source: Lexicomp,
34
unless otherwise stated.
Crowson et al
32