Lipoflavonoid® - Medical Treatment of Meniere’s Disease


Medical Treatment of Meniere’s Diease

William H. Slattery III, MD, and Jose N. Fayad, MD

 Meniere’s disease is an idiopathic disease involving the inner ear that is characterized by vertigo, hearing loss, and tinnitus. The hearing loss is fluctuating, usually low-frequency, often flat, sensorineural in type, and associated with tinnitus. The vertigo is a spontaneously occurring sensation of movement that is accompanied by unsteadiness and lasts from minutes to hours. The definitive spell varies in severity, is often prostrating, and is frequently accompanied by nausea and vomiting. The patient is oriented and conscious throughout the spell, and there are no neurologic sequelae.

The aim of this paper is to review the pharmacologic therapy used in treatment of Meniere’s disease. The first portion of this chapter will discuss the treatment of acute labyrinthine crisis that will include medications that provide relief to patients of the nausea, vomiting, and vertigo that accompanies the acute attack. Although these medications provide symptomatic relief, they are not thought to reverse the original pathologic process of Meniere’s disease but only control the symptoms. The second half of the chapter will discuss medications used to help prevent attacks of Meniere’s disease.

Nonsurgical treatment of Meniere’s disease is considered effective in approximately 80% of Meniere’s disease patients and forms the primary mode of therapy in managing these patients. There is a lack of understanding regarding the pathophysiology of Meniere’s disease, and hence the pharmacologic therapy lacks the same scientific understanding. This lack of understanding of the exact pathophysiology of Meniere’s disease is partially because of a lack of an animal model. Very few well-controlled clinical trials have been carried out evaluating medical therapy of Meniere’s disease. Most medical therapy is based on clinical experience and many medications were discovered serendipitously. The fluctuant nature of the disease makes it very difficult to conduct well-established controlled trials evaluating medical therapy. Furthermore, Meniere’s disease or symptoms may be the outward expression of different etiologies of a diseased ear, further complicating our understanding of the pathophysiology. The treatment of patients suffering from Meniere’s disease continues to be controversial. The wide variety of proposed treatments attests to the difficulty in attaining a satisfactory therapeutic result in these patients.

In 1977, Nicholas Torok published a 25-year review of 834 papers concerned with the treatment of Meniere’s disease.[17] He concluded that although treating the patient was important, the specific nature of the disease bore little relation to the therapeutic outcome. The ability to control vertiginous attacks with all medical therapies ranged between 60% and 80%. Only a small number had hearing improvement and tinnitus reduction. The therapeutic results were similar despite multiple medical regimens. The lack of rationale behind many of the proposed treatments provides support for the concept that Meniere’s disease patients benefit from a nonspecific form of therapy.

In 1991, Ruckenstein et al reviewed a significant body of literature regarding medical and surgical treatment of Meniere’s disease since the Torok study.[11] They concluded that no treatment directed at alleviating hydrops had been shown to specifically ameliorate the symptoms of Meniere’s disease, that the pathophysiologic mechanisms involved in a Meniere’s attack had yet to be elucidated, and that although hydrops is the end result, it may not necessarily be the effector of the disease process. They also found that vestibular suppressants are the only medications that have definitely been shown to improve symptoms of Meniere’s disease. They were unable to find any well-controlled study when critically re- viewed that demonstrated any medications that are able to prevent symptoms of Meniere’s disease. The lack of well-controlled studies with Meniere’s disease was discussed earlier.

Medical therapy for Meniere’s disease has classically included dietary modifications, physiotherapy, psychologic support, and pharmacologic intervention. Nonspecific modalities, such as physiotherapy, may have some value in teaching patients coping strategies. Patients also invariably benefit from a supportive and reassuring therapeutic environment.

The remainder of this section deals with the medical treatment, that is, pharmacologic intervention.

From the House Ear Clinic (WHS, JNF), and Clinical Studies Department, House Ear Institute (WHS), Los Angeles, California

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA
Volume 30 - Number 6 - December 1997

 

MEDICAL MANAGEMENT OF ACUTE VERTIGO

Pathophysiology
In vestibular disorders, the ultimate reason for the symptoms is an imbalance between the two labyrinths. To achieve recovery this imbalance must be resolved. Participating in the recovery, the central vestibular system creates a new equilibrium. Compensation involves a modification of the cholinergic brainstem synapses and results in new synapses with an asymmetric distribution pattern in both number and sensitivity. The reafferented neurons will regain their normal firing rate and come under the control of the intact labyrinth. The vestibular nuclei have several transmitter substances, both cholinergic and histamine (HI) receptors. In addition to the intervestibular connection, the cerebellar Purkinje’s cells through the y-aminobutyric acid (GABA)-ergic system increase the number of inhibitory synapses that assist in regaining the activity of the deafferented side. An adrenergic system projecting from the brainstem into the vestibular nuclei also causes inhibition of vestibular neural activity. This involves the reorganization of the intervestibular connections. It now can be understood that different drugs may exert a powerful effect on vestibular compensation.

Different classes of drugs have been used to treat vertigo. These include benzodiazepines (diazepam [Valium]), antihistamines [HI-blockers], potent anticholinergics, betahistine, ACE inhibitors, calcium antagonists, beta-blockers, carbonic anhydrase inhibitors, dopamine D2 antagonists, tricyclic antidepressants (which act as adrenomimetics), and vasodilators (histamine analogues).

ACUTE EPISODE
Vestibular suppressant drugs and antiemetics are used in the acute period (Table 1). The site of action for control of vertigo of many of these drugs remains unknown. They may act centrally at neurotransmitter sites, or peripherally on the labyrinth. These drugs have a very well-established record in controlling acute attacks of vertigo and accompanying nausea and vomiting. They have variable anticholinergic, antiemetic, and sedative properties. These drugs include benzodiazepines (diazepam), meclizine (Antivert, Bonine), prochlorperazine (Compazine), promethazine (Phenergan), diphenhydramine (Benadryl), dimenhydrinate (Dramamine), hyoscine, and metoclopramide.

Table 1. ACUTE VERTIGO TREATMENT
Vestibular Suppressants Antiemetics
Benzodiazepines Anticholinergic
Diazepam Glycopyrrolate
  Antidopaminergic
  Droperidol
  Prochlorperazine
  Antihistamines
  Dimenhydrinate
  Diphenhydramine
  Meclizine
  Promethazine

Vestibular Suppressants

Diazepam (Valium)

Diazepam acts as a vestibular depressant. It is believed to reduce the vestibular imbalance. The effect of diazepam on vestibular improvement is presumed to be due to an increase in the cerebellar GABA-ergic system that mediates inhibition on the vestibular response. This drug is useful in vertigo -when it is particularly associated with anxiety. The usual dose in Meniere’s disease for adults is 5 mg orally every 3 hours. An initial dose of 5 mg also can be given intravenously. Daytime sedation and hangover are the most common initial untoward effects of benzodiazepines. Other common side effects include dizziness, incoordination, and ataxia. Respiratory depression, apnea, and cardiac arrest have occurred rarely after intravenous administration. These reactions are more common in the elderly or severely ill patient. Benzodiazepines may exacerbate ventilatory failure in patients with severe, chronic obstructive pulmonary disease (COPD) and generally should not be used in patients with this condition or sleep apnea.

Antiemetic Drugs

Anticholinergic

Glycopyrrolate (Robinul). Glycopyrrolate is an anticholinergic medication that, when combined with diazepam, is particularly helpful in controlling inner ear symptoms of nausea and vomiting. The typical adult dose is 1 to 2 mg in the oral tablet. It may be given as an intramuscular injection with 0.1 to 0.2 mg every 4 hours. It has three reversible side effects: it may produce dryness of the mouth, distort visual acuity, or exacerbate symptoms of prostate hypertrophy. Glycopyrrolate is relatively contraindicated in patients with glaucoma and symptomatic prostatic hypertrophy.

Antidopaminergic

Droperidol (Inapsine). This butyrophenone has been used occasionally to alleviate nausea and vomiting in Meniere’s syndrome. Extrapyramidal reactions, hypotension, and sedation occur less frequently and are less severe with droperidol than with phenothiazines. The adult dose is 2.5 to 10 mg orally or 5 mg intravenously.

Prochlorperazine (Compazine). This is a piperazine phenothiazine and is used as an antiemetic and psychic inhibitor and as potentiator of analgesic and hypnotic drugs. The usual recommended dose is 10 mg given orally or intramuscularly every 4 to 6 hours. It is considered by most authorities to provide the greatest antiemetic effect of the phenothiazines. Minimum doses may induce drowsiness and mild hypotension in as many as 50% of the patients. With therapeutic doses, some patients develop an extrapyramidal reaction similar to Parkinson’s disease, with spasmodic contractions of the face and neck muscles, extensor rigidity of the back muscles, carpopedal spasm, and motor restlessness. Larger doses can cause obtundation, miosis, severe hypotension, tachycardia, stiffness of muscles, convulsions, and coma. Abnormal cardiac conduction may occur, resulting in prolongation of QRS or QT intervals or both and ventricular arrhythmias.

Antihistamines

Dimenhydrinate (Dramamine). This chlorotheophylline salt of diphenhydra- mine is especially useful in preventing and treating vertigo associated with Meniere’s disease. It also is very effective on nausea and vomiting. Mild drowsiness may occur. The dosage is 50 to 100 mg three to four times a day. The drug can also be administered intravenously and intramuscularly.

Diphenhydramine (Benadryl). Although diphenhydramine is not typically thought of in the acute treatment of vertigo, this antihistamine is useful in the prevention and treatment of vertigo, motion sickness, and nausea and vomiting. The duration of action is 4 to 6 hours. In recommended doses, the incidence of drowsiness is high. Individuals whose activities require alertness should not use diphenhydramine. The usual initial dose is 50 mg orally.

Meclizine (Anti vert, Bonine). Meclizine is one of the most useful antiemetics to prevent and treat nausea and vomiting associated with vertigo of vestibular origin. It has a slower onset and longer duration of action (24 hours) than most other antihistamines used for the same reason. Drowsiness, blurred vision, dry- ness of the mouth, and fatigue have occurred after the administration of this drug. For vertigo, the usual dose is 25 to 100 mg daily in divided doses, depending on the clinical response.

Promethazine (Phenergan). Unlike other phenothiazines, promethazine has pronounced antihistaminic activity in addition to strong central cholinergic blocking activity. It is effective in the treatment of vertigo and motion sickness. The usual dosage for treatment of nausea and vomiting in adults is initially 25 mg, then 12.5 to 25 mg as needed every-4 to 6 hours. One advantage of this drug is that it may be given rectally when severe nausea prevents oral administration. The most frequent and prominent side effect is sedation. In the usual antiemetic dose, promethazine is relatively free of the extrapyramidal reactions associated with other phenothiazine derivatives.

MAINTENANCE THERAPY

The goal of maintenance therapy is to prevent the acute attacks of vertigo and maintain hearing in Meniere’s disease. Maintenance therapy usually includes diet modifications combined with other pharmacologic interventions. The specific pharmacologic agent used in maintenance therapy may depend upon the patient’s previous response to therapy. Past experience with certain medications may prove beneficial in the selection of a specific type of maintenance therapy. The duration of maintenance therapy also is selected by the physician based on the patient’s response to therapy. Because of the fluctuant nature of the disease, long-term maintenance therapy usually is not recommended. However, some patients require continuous maintenance therapy to prevent acute attacks of vertigo and maintain hearing.

Diet Modifications

The mainstay of diet modifications is to reduce sodium intake. A very low- sodium intake or low-sodium diet is recommended. The definition of a low-sodium diet must be discussed with the patient. A strict low sodium diet with a daily allowance of 1500 mg of sodium per day is advised. This is a very stringent diet, and many patients consider this unpalatable. Patient compliance with this type of diet may be poor. A more practical approach is to ask patients to avoid excessively salty foods, to not add table salt to foods when they are being prepared, and to not add table salt to foods once they are placed on the table. This is a more practical diet that leads to better patient compliance. Encouraging a salt substitute for those with discriminating taste is helpful. Patient compliance with the practical low sodium diet is usually very well-tolerated in Meniere’s disease patients. Some patients who are very compulsive may prefer the 1500 mg per day diet. Restriction in the intake of caffeine, nicotine, and alcohol also is suggested for Meniere’s disease patients.

Diuretics

The use of diuretics stems from the supposition that these drugs can alter the fluid balance in the inner ear, leading to a depletion of endolymph and a correction of hydrops.

In 1934 Furstenberg et al demonstrated that the symptoms of Meniere’s disease were due to retention of sodium. They recommended a low salt diet and demonstrated the effects of diuretics in controlling the attacks of vertigo.[4] In 1975 Boles et al described the University of Michigan experience with a low salt diet supplemented when necessary with the use of diuretics[2]. Overall they found that most patients had their vertigo attacks controlled with an 800 to 1000 mg of sodium per day diet. Additional diuretic medical therapy was dictated by the patient’s response to low salt diet and diuretics. In 1981 Jackson et al reported the Otology Group experience in sodium restriction and found a success rate of 57.9% with this therapy.[5]

Thiazide Diuretics

In 1962 Norell and colleagues were the first to report the use of hydrochlorothiazide (HCTZ) for the treatment of Meniere’s disease.[9] Then Klockhoff and Lindblom in 1967 were the first to conduct a double-blind study on the effects of HCTZ.[6] This is one of the few attempts at a double-blind trial evaluating the effects of pharmacologic treatment of Meniere’s disease. They found HCTZ effective in controlling Meniere’s symptoms in 75% of the 50 patients. There was no effect with the placebo therapy. Van Deelen and Huizing conducted a double-blind crossover study on the effect of triamterene (Dyazide) in the treatment of Meniere’s disease.[18] In this study Dyazide controlled symptoms in 51 % of the patients whereas placebo tablets were effective in < 10% of the patients. Unfortunately, Dyazide had no effect on the hearing or tinnitus complaints in this group of pa- tients. Vertigo control was the main benefit demonstrated.

Thiazide diuretics induce a diuresis by blocking sodium absorption in the proximal portion of the nephron’s distal tubule. The complications of their usage are well-known; these include potentially arrhythmogenic hypokalemia, hyperglycemia, hyperuricemia, hypotension in previously normotensive individuals, and hyperlipoproteinemia.

Hydrochlorothiazide. These agents block sodium reabsorption in the cortical diluting segment at the terminal portion of the loop of Henle and in the proximal portion of the distal convoluted tubule. The result is natriuresis and kaliuresis. Adverse reactions to the thiazide diuretics include hypokalemia and intravascular ~ volume depletion with resulting prerenal azotemia, skin rashes, neutropenia and thrombocytopenia, hyperglycemia, hyperuricemia, and hepatic dysfunction. Potassium supplementation usually is required. The typical adult oral dose is 50 mg per day.

Dyazide. Dyazide is a combination of HCTZ and triamterene, a potassium sparing diuretic. This allows one-pill therapy without the necessity of potassium supplementation that usually is required with the use of hydrochlorothiazide. The typical adult dose is one tablet per day.

Furosemide (Lasix). Furosemide is a loop diuretic that inhibits chloride reabsorption in the ascending loop of Henle, which results in natriuresis, kaliuresis, and metabolic alkalosis. The major adverse reaction to loop diuretics relates to their potency; patients often develop excessive diuresis with resultant intravas- cular volume depletion, prerenal azotemia, and hypotension. When compared to thiazide diuretics, loop diuretics may lead to electrolyte and volume depletion more readily than the thiazides, and they also have short duration of action. Hypokalemia, particularly with accompanying digitalis therapy, is a major problem. Less common side effects include skin rashes, gastrointestinal distress, and oto- toxicity (the latter more common with ethacrynic acid). The usual adult dose is 10 to 80 mg per day, the onset of action is 15 minutes, and the duration is 4 hours.

Amiloride (K sparing). Amiloride acts on the distal tubule to reduce potassium secretion. Its diuretic potency is limited. Usually it is used in combination with other diuretics and tends to minimize the loss of potassium. Moduretic is a combination of HCTZ and arni1oride. Side effects include hyperkalemia, gastro- intestinal symptoms, and renal dysfunction.

Carbonic Anhydrase Inhibitors

Following the observation in 1949[1a] that large doses of sulfanilamide produced diuresis in edematous patients with congestive heart failure and the recognition that the diuresis resulted from inhibition of carbonic anhydrase in the renal tubules by Roughton in the early 1930s, acetazolamide, the first orally administered sulfonamide diuretic, was introduced.

Acetazolamide (Diamox). Acetazolamide inhibits sodium bicarbonate reabsorption in the proximal tubule. This causes a decrease in the sodium-hydrogen exchange in the renal tubule, thus inducing a diuresis. There is no significant increase in chloride excretion and, after several days of continuous administration, a mild hyperchloremic acidosis develops. Tolerance develops to the diuretic action in the presence of this acid-base disturbance.

Corvera[2a] reviewed their long-term experience with acetazolamide in treating Meniere’s disease. In this study they found acetazolamide as effective as chlorthalidone in controlling vertigo spells. Both of these drugs were equally effective at improving short-term hearing results; however, neither was able to prevent long-term hearing deterioration typically seen in Meniere’s disease. They suggested that an improvement in hearing demonstrated after acetazolamide administration can help confirm the diagnosis of Meniere’s disease. Although acetazolamide may be useful for management of the exacerbations of vertigo, it is not helpful in preventing long-term hearing deterioration.

This drug may cause paresthesias, gastrointestinal disturbances, anorexia, drowsiness, fatigue, and transient myopia. It also reduces the excretion of uric acid, and there is a potential of gout exacerbation during acetazolamide therapy. This diuretic is not helpful in long-term treatment for Meniere’s disease because of the above-mentioned characteristics. The usual dose is 250 mg twice daily or a 500 mg timed-release preparation for a short period of time.

Methazolamide (Neptazane). Methazolamide is another carbonic anhydrase inhibitor shown to be effective in controlling the symptoms of Meniere’s disease in the majority of the patients, and is recommended as a possible alternative for the routine thiazide diuretic therapy. The usual dosage of the medication is 50 mg per day, 5 days a week for 3 months. The dose can be increased to 50 mg three times a day. Potassium supplementation is increased initially. Side effects include skin rash, headaches, and diarrhea. Contraindications to this medication include sulfa allergy, chronic obstructive lung disease, liver failure or dysfunction, and renal failure or dysfunction.[16]

 

ABLATIVE THERAPY

Aminoglycosides

The ototoxic effects of arninoglycosides are well known. Streptomycin and gentamicin are predominantly vestibulotoxic. Schuknecht established the standard indications and the treatment regimen for systemic streptomycin use.[14] Intramuscular injections of streptomycin administered twice daily for periods of days to weeks have been used in patients with debilitating bilateral disease or unilateral disease in the only hearing ear. Silverstein et al and Moretz et al reported control of vertigo in almost all patients using this method.[8,15] Complete ablation has resulted in disabling oscillopsia. Many authors have suggested the use of lower dosages and fewer injections to achieve partial ablation of the labyrinth, reducing the severity of the ataxia but still controlling vertigo attacks and perhaps stabilizing hearing. Administration of low doses of intramuscular streptomycin is the treatment of choice for bilateral Meniere’s disease.

The current recommended daily dosage is 1 gm of streptomycin intramuscularly 5 days a week until vestibular ablation occurs as demonstrated by absence of ice water caloric test.

Intratympanic injections of streptomycin or gentamicin will be discussed in another chapter.

OTHER MEDICATIONS

Vasodilators

The use of vasodilators is based on the idea that Meniere’s disease results from ischemia of the stria vascularis. The relationship between ischemia and hy- drops has never been established.

Betahistine (Serc), a congener of histamine, has been evaluated. Although the available studies are small and the rationale for its use is somewhat obscure, the literature does offer some support of the use of betahistine for the short-term control of vertigo and for maintenance therapy. Several double-blind placebo controlled trials have demonstrated the efficacy of betahistine in controlling the vertigo, nausea, and vomiting associated with acute Meniere’s crisis. No difference in the hearing levels was noted. Mild stomach discomfort may be seen with administration of betahistine.[3,10] Other placebo controlled double-blind crossover studies have not been able to demonstrate efficacy of betahistine.[13]

Betahistine dihydrochloride, a derivative of histamine, can be taken orally. Betahistine dihydrochloride relaxes the precapillary sphincters and, thus improves the microcirculation of the inner ear. The antivertigo action of betahistine is explained as the result of an inhibition of the massive impulses to the polysynaptic neurons of the lateral vestibular nucleus. It has a dose-response effect on vestibular nystagmus induced by means of torsion swing, and does not have any central sedative effects, as measured by saccadic eye movements. The usual dosage is 8 mg three times daily. It is considered by certain authors to be the most effective drug in maintenance therapy for Meniere’s disease. It has minimal side effects and it has not been shown to slow down habituation. [1]

Nicotinic acid is given about 30 minutes before meals in doses of 50 to 400 mg depending on how much is necessary to produce a good flush. Some patients require much more nicotinic acid than others.

Calcium Channel Blockers

Nimodipine is a highly lipophilic agent that readily crosses the blood-peri- lymph barrier and has recently been demonstrated to be effective in the medical treatment of Meniere’s disease in patients who have failed diuretic medical therapy.

Nimodipine is currently approved by the Food and Drug Administration for the reduction of cerebrovasospasm following subarachnoid hemorrhage. The mechanism of action is thought to be related to manipulation of calcium concentrations within the inner hair cells or due to central modulation resulting from the peripheral vestibular irritation. The recommended dosage is 30 mg twice a day. Gastrointestinal upset is the most common side effect; another problem with this medication is the cost.[7]

ACE Inhibitors

ACE inhibitors are very effective vasodilators. These agents block the reninangiotensin aldosterone system. They produce vasodilation by blocking angiotensin II induced vasoconstriction, but they also inhibit the degradation of bradykinin, increase the production of vasodilating prostaglandins, and inhibit the adrenergic nervous system. They increase sodium excretion by inhibiting aldosterone production and improve the ability of the kidneys to excrete free water by unknown mechanisms. The major limitations of ACE inhibitors are hypotension and renal insufficiency; other side effects include skin rashes, taste alterations, cough, neutropenia, and proteinuria.

Lipoflavins and Vitamins

Eriodictyolglycoside (lemon bioflavonoid extract) may act on histidine decarboxylase or on the storage, release, or destruction of one of the amines or one of the polypeptides, or both, that appear to playa major part in control of the microcifculation. Schayer had stated "All the observations seem to be unified by the hypothesis that inducible histidine decarboxylase is located in or close to, vascular endothelial cells and synthesizes histamine at a rate determined by the requirements of the tissues for blood.12 Williams et al wrote, "Histamine suddenly induced by a local stimulus in quantities far beyond homeostatic necessity would reproduce the symptoms, signs and pathologic [condition] of Meniere’s disease."[19]

It is therefore hypothesized that a stimulus of unknown origin may induce histidine decarboxylase in amounts greatly in excess of homeostatic needs, with the synthesis of toxic amounts of histamine that then produce a paralytic dilatation of the blood vessels of the stria vascularis, with the subsequent histologic picture and distension of the endolymphatic system. Eriodictyolglycoside may act as a blocking agent for histidine decarboxylase.

Williams reported 122 cases of Meniere’s disease treated with lemon bioflavonoid complex and found a beneficial effect on vertigo and hearing in these patients (Table 2).[19] The physiologic mechanism by which this effect is produced is unknown.

Table 2. CONTENTS OF LlPO-FLAVONOID CAPSULE
Each three capsules of lipoflavonoid contain:
Lemon bioflavonoid complex (bioflavonoids)
300mg
Ascorbic acid
300mg
Choline
334 mg
Inositol
334 mg
dl-Methionine
84 mg
Thiamine
1 mg
Niacin
10mg
Pyridoxine hydrochloride (B6)
1mg
Cyanocobalamin (B12) concentrate
5mg
Pantothenic acid
5mg
Riboflavin
1mg
Lemon bioflavonoid complex is a hygroscopic dried powder containing water-soluble flavonoids. The product contains small quantities of hesperidin, citronin, and diosmin. These glycosides can be obtained only from lemon; they cannot be obtained from oranges or any other citrus fruit. The usual dose is 2 capsules 3 times a day for a trial period of 6 months or more.

RECOMMENDED THERAPY

In Meniere’s disease, an attempt is made to suppress the vestibular symptoms and to treat the underlying pathologic feature of endolymphatic hydrops. The therapeutic efficacy of drugs used to manage vertigo associated with this disorder is difficult to evaluate because spontaneous remission may occur.

For treatment of acute vertigo we recommend oral diazepam. Diazepam controls the symptoms of nausea, vomiting, and vertigo seen with Meniere’s disease in the majority of patients. In refractory cases, meclizine 25 to 100 mg orally, dimenhydrinate 50 mg orally or intramuscularly, hyoscine 0.6 mg subcutaneously, droperidol5 mg intravenously, or diazepam 5 to 20 mg slowly intravenously may be required. Dehydration and electrolyte disturbances caused by vomiting should be corrected.

Maintenance therapy is directed toward preventing the acute vertiginous spells; diet control and diuretics are typically recommended. We prefer 50 mg of hydrochlorothiazide supplemented with potassium or Dyazide as initial diuretic therapy. In addition, vasodilators may be considered in individuals refractory to diuretic therapy. The use of papaverine, histamine, betahistine, and other vasodilators to improve blood flow to the labyrinth and brainstem has temporarily relieved vertigo, but their role in the symptomatic treatment and in arresting progression of Meniere’s disease has not been defined adequately.

References

1. Aantaa E: Treatment of acute vestibular vertigo. Acta Otolaryngol Suppl (Stockh) 479:44, 1991
la. American Medical Association Drug Evaluations 1994. Chicago, American Medical Association, 1994, p 820
2. Boles R, Rice DH, Hybels R, et al: Conservative management of Meniere’s disease: Fur- stenberg regimen revisited. Ann Otol Rhinol Laryngol 84:513, 1975
2a. Corvera J, Corvera G: Long-term effect of acetazolamide and chlorthalidone on the hear- ing loss of Meniere’s disease. Am J Otoll0:142-145, 1989
3. Fraysse B, Bebear JP, Dubreuil C, et al: Betahistine dihydrochloride versus flunarizine. A double-blind study on recurrent vertigo with or without cochlear syndrome typical of Meniere’s disease. Acta Otolaryngol Suppl (Stockh) 490:1, 1991
4. Furstenburg AC, Lashmet FH, Lathrop F: Meniere’s symptom complex: Medical treatment. Ann Otol Rhinol LaryngoI43:1035, 1934
5. Jackson CG, Glasscock ME III, Davis WE, et al: Medical management of Meniere’s disease. Ann Otol Rhinol Laryngol90:142, 1981 I
6. Klockhoff I, Lindblom U: Meniere’s disease and hydrochlorothiazide (Dichlotride}-A critical analysis of symptoms and therapeutic effects. Acta Otolaryngol (Stockh) 63:347, 1967 7. Lassen LF, Hirsch BE, Kamerer DB: Use of nimodipine in the medical treatment of Me- niere’s disease: Clinical experience. Am J OtoI17:577, 1996
8. Moretz WH, Shea JJJ, Orchik DJ, et al: Streptomycin treatment in Meniere’s disease. Otolaryngol Head Neck Surg 96:256,1987
9. Norrell I, Stahle J: Treatment of Meniere’s disease with hydrochlorothiazide. Acta Oto- laryngol (Stockh) 54:447, 1962
10. Oosterveld WJ: Betahistine dihydrochloride in the treatment of vertigo of peripheral vestibular origin. J Laryngol Otol 98:37, 1984
11. Ruckenstein MJ, Rutka JA, Hawke M: The treatment of Meniere’s disease: Torok revi ited. Laryngoscope 101:211,1991
12. Schayer RW: Significance of induced synthesis of histamine in physiology and pathology. Chemotherapia 3:128,1961
13. Schmidt IT, Huizing EH: The clinical drug trail in Meniere’s disease with emphasis on the effect of betahistine SR. Acta Otolaryngol SuppI497:1, 1992
14. Schuknecht HF III: Ablation therapy in the management of Meniere’s disease. Acta Otolaryngol Suppl132:1, 1957
15. Silverstein H, Hyman SM, Feldbaum J, et al: Use of streptomycin sulfate in the treatment of Meniere’s disease. Otolaryngol Head_Neck Surg 92:229,1984
16. Slattery WH III, Singleton GT: Methazolamide as medical therapy for the control of symptoms of Meniere’s disease. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery. San Diego, CA, 1994
17. Torok N: Old and new in Meniere disease. Laryngoscope 87:1870, 1977
18. van Deelen GW, Huizing EH: Use of a diuretic (Dyazide(r" in the treatment of Meniere’s disease: A double-blind cross-over placebo-controlled study. ORL J Otorhinolaryngol Relat Spec 48:287,1986
19. Williams HL, Maher FT, Corbin KB, et al: Eriodictyol glycoside in the treatment of Meniere’s disease. Ann Otol Rhinol Laryngol72:1082, 1963


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William H. Slattery III, MD
Clinical Studies Department
House Ear Institute
2100 West Third Street, 5th Floor
Los Angeles, CA 90057-9927