MENIERE’S DISEASE — DO DIURETICS HAVE A ROLE IN THERAPY TODAY?
In the treatment of Meniere’s disease, diuretics have lost the pride of place that they once enjoyed. Diuretics appear to have fallen out of favour with most contemporary neurotologists. When it comes to choosing a drug for Meniere’s disease (MD), Betahistine is the first choice for most of the neurotologists.
However, in my clinical practice of Neurotology, I have had a flawless experience with diuretics in the management of Meniere’s disease. So, I didn’t have a compelling reason to prefer Betahistine over diuretics for most patients with recurrent Meniere’s disease.
I know this goes against what’s generally accepted, and I’m sharing my thoughts with some hesitation. My main goal is to get some clarity and make sure my reasoning isn’t flawed. This is one of the highest academic forums in Neurotology today, and I would like to have my doubts cleared, even if it stirs a hornet’s nest.
The logic in favour of BETAHISTINE in confirmed Meniere’s disease did not appear very convincing to me, despite all the scientific propaganda and Cochrane reports telling us that Betahistine is the drug of choice.
Understanding Meniere’s Disease: The Hydrops Connection
The Merriam-Webster Medical dictionary defines Hydrops as the distension of a hollow organ with fluid. If Meniere’s disease is accepted as endolymphatic hydrops, then the very definition implies that there is distension due to excessive fluid collection.
If we accept this pathophysiology, then the antidote for any oedema or fluid collection can be nothing other than agents that will drain out the fluid, which are DIURETICS, and drugs that will reduce the secretion of fluids in the region.
However, the use of diuretics has not become the generally accepted mode of treatment in endolymphatic hydrops like Meniere’s disease. Till the mid-80s, diuretics were found beneficial in MD. Although the perceptions have changed now. DIURETICS have now been dumped in favour of Betahistine.
Debunking the Cochrane Review
The 2010 Cochrane Database review often challenges the use of diuretics for Meniere’s disease. Burgess and Kundu wrote the article titled “Diuretics for Meniere’s Disease or Syndrome (review)”. It was published by the Cochrane Collaboration in 2010.
They said there wasn’t enough strong evidence to prove that diuretics help. Most studies were poorly designed or didn’t use proper trials.
They didn’t say diuretics don’t work. They stated that the research is too weak to confirm their benefit.
Clinical Experience & Rationale for Diuretics
There are 3 ways a drug can exert beneficial effects in Hydrops-
- First, by draining away the fluid
- Second, by decreasing the generation of the fluid
- Lastly, by changing the electrolyte composition in the inner ear.
Diuretics are capable of all of them. Indeed, the hearing improvement or decrease in tinnitus is not appreciable in long-term use in most patients, but it does not mean that diuretics do not have any effect. Diuretics induce dehydration and drainage of fluid from the inner ear, which causes a temporary benefit, and is evident in the Glycerol/furosemide dehydration test for the diagnosis of Meniere’s disease. Diuretics effectively reverse pathology, even if not permanently. While hearing improvements may not last, studies show diuretics offer long-term relief for vestibular symptoms.
Endolymphatic hydrops is considered to be the principal histopathologic characteristic in temporal bones from patients with, Meniere’s disease. ACETAZOLAMIDE is a Carbonic anhydrase inhibitor.
Inner Ear Fluid and Carbonic Anhydrase Inhibitors
Inner ear perilymph can become more concentrated independently of blood osmolality. This is significant for understanding carbonic anhydrase inhibitors. These inhibitors increase the excretion of bicarbonate, sodium, potassium, and water. This fluid-reducing effect is crucial in treating glaucoma, a condition characterized by excessive aqueous humor buildup in the eye. By decreasing fluid secretion, these inhibitors effectively manage glaucoma.
Evidence Supporting Diuretics
Heidechi and Kimura conducted a study published in Acta Otoaryngologica (1986) titled “Effects of Diuretics in Endolymphatic.” They induced endolymphatic hydrops in 77 albino guinea pigs by blocking the endolymphatic sac and duct. One month of acetazolamide treatment suppressed hydrops in the cochlea, saccule, and utricle.
They observed minimal dilatation in the semicircular canals. The study was double-blind and placebo-controlled. It showed that acetazolamide prevented the level of distension seen in untreated animals.
This evidence supports the role of diuretics in Meniere’s disease management.
Some published reports of symptomatic improvements in patients with Meniere’s disease following acetazolamide administration:-
1. Corvera J. Carbonic anhydrase and internal ear. Ann OtolRhinolLaryngol1956; 65: 351-5.
2. Muftic MK. Acetazolamide in Meniere’s disease. Arch Otolaryngol1957; 65: 575-9.
3. Varga G, Miriszlai E, Szab6 LZ. Experiences with acetazolamide therapy applied in our clinic to patients suffering from Meniere’s disease for more than 8 years. J LaryngolOtol1966; 80: 250-69. 14
Animal experiments :-
4. H. Shinkawa and R. S. Kimura, Effect of Diuretics on EndolymphaticHydropsActaOtolaryngol (Stockh)1986; 101: 43-52
Some studies that have shown improvements with diuretics in Meniere’s disease are as follows:-
1967 Klockhoff + Lindblom – Htcz in DB trial – improvement in vertigo and deafness.
1974 Klockhoff + Lindblom – Chlorthalidone 7yr follow-up showed – improvement in 76% pts.
1986 Deelen + Huizing Triamterene + Hctz – improvement only in vertigo
Mechanism of action of diuretics, as suggested in literature are:-
Carlberg + Farmer (1983) suggested that – osmotic diuretics like glycerol / furosemide cause rapid dehydration followed by a decrease of inner ear pressure
Klockhoff + Lindblom (1967) suggested that diuretics not only cause dehydration but possibly also have effects on labyrinthine electrolyte regulation
Deelan + Huizing (1986) – postulated that themechanism by which Diazideincreases excretion of Sodiumbut decreases excretion of Pottasiumion transport mechanism in the renal tubules and striavascularis of the inner ear is the same. The authors suggested that long-term diuretics have an effect on the function of striavascularis and consequently on electrolyte regulation in inner ear.
Intratympanic Gadolinium-Enhanced MRI: A Key to Understanding Endolymphatic Hydrops
Intratympanic (IT) gadolinium-enhanced MRI is currently the most reliable test for endolymphatic hydrops. It likely offers greater specificity than electrocochleography.
A 2009 study by Miyagawa et al., published in Acta Oto-Laryngologica (129: 1326-1329), demonstrated that diuretics can reverse endolymphatic hydrops. Their paper, “Endolymphatic hydrops and therapeutic effects are visualized in ‘atypical’ Meniere’s disease,” showed complete reversal of hydrops in the cochlea’s basal turn. Patients treated with the osmotic diuretic isosorbide for 350 days experienced a return to normal hearing.
Conclusion
Diuretics do have a positive role in the therapy of Meniere’s disease. It is evidence-based, ethical, and scientifically logical. Betahistine possibly also has a positive role in Meniere’s disease as evidenced by many studies, but the mechanism of action is not as clear as that of Diuretics.
The action of Betahistine may be at least partly due to its symptom-relieving vestibular sedative effect, and if so, long-term use is not justifiable.
The use of DIURETICS like ACETAZOLAMIDE/ FUROSEMIDE / HYDROCHLOROTHIAZIDE/ TRIAMTERENE / SPIRONOLACTONE needs a rethink and re-acceptance for treatment of Meniere’s disease.