Medicare Program; Noncoverage of Electrostimulation of Salivary Glands for the Treatment of Xerostomia (Dry Mouth)

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Health Care Financing Administration

[BPD-782-PN]

RIN 0938-AG45

Medicare Program; Noncoverage of Electrostimulation of Salivary

Glands for the Treatment of Xerostomia (Dry Mouth)

AGENCY: Health Care Financing Administration (HCFA), HHS.

ACTION: Proposed notice.

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SUMMARY: This notice announces the Medicare program's proposal not to

cover electrostimulation of the salivary glands for the treatment of

xerostomia secondary to Sjogren's syndrome, and electrostimulation

devices, such as the Salitron System. Public Health Service (PHS)

studies show that there are insufficient data to establish the clinical

utility of electrostimulation, to evaluate its long-term effectiveness,

and to identify those xerostomia patients who would benefit from this

procedure. Also, PHS reports that electrostimulation is not widely

accepted as a treatment for xerostomia secondary to Sjogren's syndrome.

Therefore, it does not meet HCFA's criteria for effectiveness.

DATES: Comments will be considered if we receive them at the

appropriate address, as provided below, no later than 5 p.m. on July

22, 1994.

ADDRESSES: Mail written comments (1 original and 3 copies) to the

following address: Health Care Financing Administration, Department of

Health and Human Services, Attention: BPD-782-PN, P.O. Box 26688,

Baltimore, Maryland 21207.

If you prefer, you may deliver your written comments (1 original

and 3 copies) to one of the following addresses:

Room 309-G, Hubert H. Humphrey Building, 200 Independence Avenue, SW.,

Washington, DC 20201, or

Room 132, East High Rise Building, 6325 Security Boulevard, Baltimore,

MD 21207.

Because of staffing and resource limitations, we cannot accept

comments by facsimile (FAX) transmission. In commenting, please refer

to file code BPD-782-PN. Comments received timely will be available for

public inspection as they are received, generally beginning

approximately 3 weeks after publication of a document, in room 309-G of

the Department's offices at 200 Independence Avenue, SW., Washington,

DC, on Monday through Friday of each week from 8:30 a.m. to 5 p.m.

(phone: (202) 690-7890).

FOR FURTHER INFORMATION CONTACT: Francina C. Spencer (410) 966-4614.

SUPPLEMENTARY INFORMATION:

I. Background

A. Program Description

Section 1862(a)(1)(A) of the Social Security Act (the Act)

generally prohibits payment for any expenses incurred for items or

services ``which, * * * are not reasonable and necessary for the

diagnosis or treatment of illness or injury or to improve the

functioning of a malformed body member.'' We have interpreted this

statutory provision to exclude from Medicare coverage medical and

health care services and items that are not demonstrated to be safe and

effective by acceptable clinical evidence. This prohibition applies to

items for which claims are submitted under Medicare's durable medical

equipment (DME) benefit.

B. Medicare Coverage of Electrostimulation of Salivary Glands for the

Treatment of Xerostomia (Dry Mouth) Secondary to Sjogren's Syndrome

Patients with chronic xerostomia complain of a continual feeling of

oral dryness, have difficulty eating dry foods, and are susceptible to

increased tooth decay, oral pain, tongue fissures, and infection.

Saliva contains proteins and enzymes that aid digestion, conduct

electrolytes necessary to maintain hard tooth enamel, and produce

antibacterial agents to control oral bacteria. Salivary gland

dysfunction leads to difficulty in speaking, chewing, swallowing, and

tasting. A decrease in salivary secretion may result from damage to the

salivary glands caused by chronic infection, irradiation, or systemic

diseases such as hypertension, diabetes, or Sjogren's syndrome.

Sjogren's syndrome is a chronic, inflammatory, and autoimmune disease

in which the salivary and tear glands undergo progressive destruction

by lymphocytes and plasma cells resulting in decreased production of

saliva and tears.

Treatment for xerostomia varies considerably. If Vitamin C tablets,

gum, and hard candy do not stimulate salivation in patients with some

salivary gland function, artificial saliva using either an atomizer or

an intraoral reservoir are used. While these methods relieve the

symptoms of chronic xerostomia, they usually offer only temporary

relief. Oral drugs such as pilocarpine and pyridostigmine are effective

in increasing salivation if there are some functioning salivary gland

tissues. However, because of side effects and contraindications, the

usefulness of these drugs is limited.

On March 27, 1987, Biosonics, Inc. requested marketing approval by

the FDA of the Salitron System. This device is a battery-powered, hand-

held electrostimulation device for stimulating salivation from existing

glandular tissue by delivering a small electrical stimulus to the mouth

using a probe with two metal electrodes. It is used for patients with

xerostomia secondary to Sjogren's syndrome with residual salivary

tissue in the oral and pharyngeal regions. Physicians use the device to

screen patients to determine a response to electrostimulation before

prescribing the system. After reviewing the recommendation of the

Dental Devices Panel, FDA's Center for Devices and Radiological Health,

the FDA granted premarket approval for the Salitron System on May 18,

1988. The approval was announced in the July 14, 1988, notice entitled

``Biosonics; Premarket Approval of the Salitron System'' (53 FR 26673).

At this time, the Salitron System is the only device approved for

marketing by the FDA for electrostimulation of salivary glands.

Currently, Medicare does not have a national policy for covering

electrostimulation of salivary production for treating xerostomia

secondary to Sjogren's syndrome. Without a national policy, Medicare

carriers have authority under section 1842(a) of the Act to make

coverage decisions within the parameters set by the statute,

regulations, and program instructions. Some carriers are paying for

electrostimulation of the salivary glands using the Salitron System and

others are not because they question the medical efficacy of the

treatment. This has resulted in inconsistent coverage policies among

carriers.

C. Recommendation Not to Cover Electrostimulation of Salivary

Production in the Treatment of Xerostomia Secondary to Sjogren's

Syndrome

On May 26, 1988, Biosonics requested that Medicare issue a national

policy decision that would provide for coverage of the Salitron System.

Based on our evaluation of their request, we consulted the HCFA

Physicians Panel. The Panel recommended that OHTA evaluate the safety

and effectiveness of the Salitron System as well as the criteria used

to identify xerostomia patients who would benefit from the device.

On October 4, 1988, we asked OHTA to conduct a full assessment of

the safety and effectiveness of the Salitron System and to develop

patient selection criteria. To conduct this assessment, OHTA solicited

information from clinicians, appropriate private organizations,

researchers, other government agencies, other components of PHS, and

the National Institutes of Health (NIH). OHTA evaluated studies, data

provided to the FDA, published articles, and information from

respondents to the March 2, 1989, notice entitled ``National Center for

Health Services Research and Health Care Technology Assessment;

Assessment of Medical Technology'' (54 FR 8829). In that notice, OHTA

announced that it was assessing the patient criteria for

electrostimulation of salivary glands for the treatment of xerostomia

secondary to Sjogren's syndrome and an electrostimulation device's

acceptability, cost, and effectiveness relative to other therapies.

On July 30, 1990, we received OHTA's assessment ``Salivary

Electrostimulation in Sjogren's Syndrome'' with a bibliography of

literature and investigations evaluating electrostimulation of salivary

glands. (A copy of this assessment is included as an addendum to this

proposed notice.)

According to OHTA, from the limited studies as well as data

provided to the FDA, it appears that electrostimulation of salivary

glands may be useful in managing xerostomia in certain patients. OHTA,

however, states that there are insufficient data to determine the

clinical utility of electrostimulation, to evaluate its long-term

clinical effectiveness, and to identify xerostomia patients who would

benefit from this procedure. Also, OHTA has determined that

electrostimulation is not widely accepted as an effective method for

treating xerostomia secondary to Sjogren's syndrome and that other

treatments, such as the use of Vitamin C tablets, gum, hard candy, and

artificial saliva, are available.

NIH advised OHTA that guidelines specifying the types and

conditions of xerostomia patients who would benefit from

electrostimulation cannot be developed without further clinical studies

of well-characterized patient populations. Given the single published

study showing that only patients with residual salivary flow in an

unstimulated state will respond to electrostimulation, NIH suspects

that those individuals are likely to respond as well to other means of

salivary stimulation.

OHTA reviewed the published study, the preliminary investigation,

and the study presented to the FDA. The 1988 study by M. Steller and

associates (``Electrostimulation of Salivary Flow in Patients with

Sjogren's Syndrome'' Journal of Dental Research 1988; 67(60): 1334

through 1337) revealed that only 3 of 13 patients using an active

device showed a significant response in salivary production when

compared to the response of the placebo device group. The 1986

preliminary investigation conducted by W. W. Weiss and associates

(``Clinical Trial of an Electronic Stimulatory Device in the Management

of Xerostomia'' Journal of Oral and Maxillo-facial Surgery November

1986: M10) did not include a control group or any quantitative

assessment of salivary response, duration of response, or long-term

assessment of efficacy. Moreover, 7 of the 9 patients tested had

residual saliva production before treatment and may have been

exhibiting a tactile response to the probe. The 1988 study by N. Talal

and associates (``The Clinical Effects of Electrostimulation on

Salivary Function of Sjogren's Syndrome Patients'' Rheumatology

International June 1992; 12(12) 43 through 45), upon which the FDA

based its approval, describes the clinical effects of

electrostimulation in 77 patients. Salivary production was measured at

the start of the study, at 2 weeks, and at 4 weeks. The researchers

reported that salivation was higher among the group using an active

device than the placebo device group. However, because of a

misunderstanding about the length of the study, about half of the

subjects dropped out of the study by the fourth week.

Thus, OHTA concluded that additional, long-term studies with larger

patient populations are needed to define the specific degrees of

salivary dysfunction that would respond to electrostimulation and to

determine how long it takes to determine if salivary glands have been

regenerated. These studies could help determine whether a single

salivary response to electrostimulation or some other test, such as a

lip biopsy, should be used to help identify those patients who may

benefit from electrostimulation. In addition, OHTA stated that to

determine the effectiveness of electrostimulation, studies should

include information regarding concomitant therapy and the duration of

the salivary response to compare the device to other therapies. Studies

and subsequent management should include quantitative assessment of

salivary function, assessment of oral conditions, and subjective

patient evaluations.

The comments OHTA received from knowledgeable clinicians were

inconsistent. Some clinicians state that electrostimulation is safe and

effective while others suggest that the method has been inadequately

tested and are not convinced that it is more effective than other

simple, less costly stimulation techniques.

After OHTA's published report, Biosonics requested review of

additional data on the use of the Salitron System. On September 21,

1990, we submitted the data to OHTA. OHTA reported on October 26, 1990,

that this data had been presented to the FDA and was included in the

OHTA assessment of July 30, 1990. OHTA concluded that the treatment

could be reassessed when additional data from a larger patient

population is available to evaluate the long-term clinical

effectiveness of electrostimulation and identify those xerostomia

patients who would benefit from an electrostimulation device.

On November 2, 1990, we submitted to OHTA another request for a

review of data from Biosonics. On November 14, 1990, OHTA informed us

that it had previously reviewed this data and referred us to its

October 26, 1990, recommendation.

On October 9, 1992, Biosonics requested a reassessment and

submitted two new articles on electrostimulation for xerostomia

published in ``Geriatric Consultant'' and ``Rheumatology

International.'' One article reported a physician's experience in

treating 33 patients for 6 months. The other article reported on the

unpublished clinical study evaluated by the FDA in 1988. We have

determined that the medical evidence and conclusions upon which OHTA's

assessment is based are still accurate based on our own medical

expertise and a thorough review of all the medical literature on the

subject since the 1990 assessment.

II. Provisions of This Proposed Notice

OHTA concluded that there are insufficient data to determine the

clinical utility of electrostimulation, to evaluate its long-term

clinical effectiveness, and to identify xerostomia patients who would

benefit from this procedure and that electrostimulation is not widely

accepted as an effective treatment for xerostomia. Based on these

conclusions, we have determined that electrostimulation of salivary

glands and the electrostimulation device, the Salitron System, do not

meet our criteria for effectiveness. Therefore, we propose to publish a

final notice announcing a national coverage decision that Medicare does

not cover electrostimulation of salivary glands for treating xerostomia

secondary to Sjogren's syndrome.

The provisions of this notice would not affect any existing

Medicare regulations. However, they would be incorporated in the

Medicare Coverage Issues Manual (HCFA Pub. 6).

III. Response to Comments

Because of the large number of items of correspondence we normally

receive on proposed notices, we are not able to acknowledge or respond

to them individually. We will consider all comments that we receive by

the date and time specified in the DATES section of this preamble, and

if we proceed with a subsequent document, we will respond to the

comments in the preamble to that document.

IV. Collection of Information Requirements

This document does not impose information collection and

recordkeeping requirements. Consequently, it need not be reviewed by

the Office of Management and Budget under the authority of the

Paperwork Reduction Act of 1980 (44 U.S.C. 3501 et seq.).

V. Regulatory Impact Statement

A. Introduction

Currently, Medicare does not have a national policy for covering

electrostimulation of salivary production for treating xerostomia

secondary to Sjogren's syndrome. Medicare carriers have authority to

make coverage decisions within the parameters set by the statute,

regulations, and program instructions. Because this service is not

ordered often and because of the low total allowed charges by Medicare

Part B for this service, less than $26,000 in calendar year (CY) 1991,

and no reported payments in CY 1992, we believe this proposed notice

would result in negligible savings during calendar years 1994 through

1998.

B. Regulatory Flexibility Act

We generally prepare a regulatory flexibility analysis that is

consistent with the Regulatory Flexibility Act (RFA) (5 U.S.C. 601

through 612) unless the Secretary certifies that a notice would not

have a significant economic impact on a substantial number of small

entities. For purposes of the RFA, all physicians prescribing and

suppliers distributing a device to stimulate salivary production from

existing glandular tissue are considered to be small entities.

In addition, section 1102(b) of the Act requires the Secretary to

prepare a regulatory impact analysis if a notice may have a significant

impact on the operations of a substantial number of small rural

hospitals. This analysis must conform to the provisions of section 603

of the RFA. For purposes of section 1102(b) of the Act, we define a

small rural hospital as a hospital that is located outside of a

Metropolitan Statistical Area and has fewer than 50 beds.

The Medicare program paid for 41 electrostimulation devices during

CY 1991 totaling an estimated $26,000 at an average cost of

approximately $630 each. It appears that carriers are no longer paying

for this electrostimulation device, thereby explaining why no invoices

for this device were processed in CY 1992. In the absence of this

notice, it is possible that the number of devices prescribed by

physicians would increase and carriers would resume payment. Physicians

have at least two alternate methods for treating xerostomia. One method

is to rely on the use of artificial saliva in conjunction with the

sipping of liquids for moisture. The second alternative is the use of

gums and candies to induce saliva. Since there are alternative

treatment methods, we believe this proposed notice would affect

physicians and beneficiaries minimally.

Therefore, we are not preparing analyses for either the RFA or

section 1102(b) of the Act since we have determined, and the Secretary

certifies, that this proposed notice would not result in a significant

economic impact on a substantial number of small entities and would not

have a significant impact on the operations of a substantial number of

small rural hospitals.

In accordance with the provisions of Executive Order 12866, this

proposed notice was not reviewed by the Office of Management and

Budget.

(Secs. 1861 and 1862 of the Social Security Act (42 U.S.C. 1395x and

1395y))

(Catalog of Federal Domestic Assistance Program No 93.774,

Medicare--Supplementary Medical Insurance)

Dated: March 3, 1994.

Bruce C. Vladeck,

Administrator, Health Care Financing Administration.

Dated: April 7, 1994.

Donna E. Shalala,

Secretary.

Salivary Electrostimulation in Sjogren's Syndrome

Number 8

Patient Selection Criteria for Electrostimulation of Salivary

Production in the Treatment of Xerostomia Secondary to Sjogren's

Syndrome

Prepared by: Martin Erlichman

Introduction

Electrostimulation has been introduced as a technique for

increasing salivary output in the treatment of patients with

xerostomia (dry mouth) secondary to Sjogren's syndrome. The

procedure uses an electrostimulation device (salivation

electrostimulator) to increase salivary production from existing

glandular tissue. The device delivers a small electrical stimulus to

the mouth via a probe. The electrostimulation device consists of an

electric control module, a connecting cord, and a hand-held stimulus

probe with two metal electrodes. The device may be battery-powered.

Patients with residual salivary tissue in the oral and pharyngeal

regions who demonstrate a decrease in the flow rate of saliva are

potential candidates for this procedure.

Xerostomia may be the result of Sjogren's syndrome, other

diseases, medications, or radiation therapy to the head and neck. To

determine that the xerostomia has resulted from Sjogren's syndrome,

clinicians also confirm the presence of keratoconjunctivitis sicca

(dry eye) and a positive lip biopsy with or without the presence of

a connective tissue disease. It is estimated that more than one

million people, mostly women, suffer from Sjogren's syndrome in the

United States.1

Xerostomia is usually defined as a symptom that exists when

saliva production is less than 0.1 mL/min (or 0.1 g/min). However,

the symptom of xerostomia has been reported to appear when normal

salivary output declines by approximately 50%, regardless of the

starting value. Normal saliva production has been estimated to be

600 mL/24h.2 Patients with chronic xerostomia complain of a

continual feeling of oral dryness and find it difficult to eat dry

foods.3 In addition to the subjective complaints, the patient

with salivary gland dysfunction is susceptible to increased dental

caries, oral pain, frequent infections, and difficulties in

speaking, chewing, and swallowing.4 Several tests are available

for measuring salivary function. According to Fox et al,5

evaluation of salivary gland function can be assessed by stimulated

saliva collection and analysis. The biopsy of the salivary glands,

usually obtained from the lower lip, is used to differentiate true

Sjogren's syndrome from other forms of salivary gland dysfunction.

The approach to the treatment of this condition varies

considerably. In some patients, xerostomia may be managed by sipping

water frequently. Other patients stimulate salivary flow with

sugarless mints or gum.6 Salivary substitutes such as a

carboxymethylcellulose-based artificial saliva have been used by

some patients to supplement low quantities of salivary flow.

Pharmacologic agents have been introduced to treat the oral dryness

of salivary gland dysfunction in patients where unstimulated

salivary flow was low or nonexistent but where some functional

salivary gland tissue existed. Fox et al4 reported that

pilocarpine was effective for relieving xerostomia by increasing

natural salivary function. The production of endogenous saliva is of

greatest benefit to the patient both for its convenience and the

importance of natural saliva to oral functions. Recently, attempts

to increase saliva production have utilized electrical stimulation.

Preliminary investigations were reported by Weiss et al7 in

1986.

This report will examine the published literature and other

available evidence to evaluate the electrostimulation of salivary

production and determine if there are xerostomic patients who would

benefit from this procedure.

Background

Sjogren's syndrome is a chronic inflammatory and autoimmune

disease in which the salivary and lacrimal glands undergo

progressive destruction by lymphocytes and plasma cells resulting in

decreased production of tears and saliva.8 Sjogren's syndrome

is seen predominantly in middle-aged elderly women.9 Females

are involved 10 times more commonly than males. Secondary effects of

xerostomia include impairment in the normal movement of lips and

tongue, thereby hampering speech, mastication, and

swallowing.10 Additional signs include oral soreness, adherence

of food to buccal surfaces, fissuring of the tongue, an altered

sense of taste, and a marked increase in dental caries and

infection. Soreness and redness of the mucosa are usually the result

of candidal infection, which is found in approximately 70% of the

Sjogren's syndrome patients.11

Complaints resulting from dryness of the mouth are varied and

often describe the difficulties encountered in trying to eat dry

foods without sufficient lubrication.11 Many subjects require

frequent ingestion of liquids. They may resort to carrying water

bottles or hard candy.

The parotid gland enlarges in many patients secondary to

cellular infiltration and ductal obstruction. Usually asymptomatic

and self-limited, the enlargement can be recurrent and associated

with pain or erythema. Focal infiltrates of lymphocytes are also

found in the minor salivary glands of the lower lip. Biopsy provides

histologic confirmation and quantification of the degree of

infiltration.

The subjective imprsssion of xerostomia, or oral dryness, may

not reflect actual salivary gland capabilities.\12\ Salivary flow

rate estimation is a sensitive indicator of salivary gland function.

A suction cup is used to obtain parotid saliva from the gland after

the tongue is stimulated with citric acid. Although the parotid

glands make the major contribution to the total salivary flow, the

submandibular glands are the most consistently affected glands in

patients with Sjogren's syndrome. Measurement of parotid function

may result in false-normal valuse. In Sjogren's syndrome,

measurement of the submandibular/sublingual secretions are a

sensitive indicator of salivary gland hypofunction. According to Fox

et al\12\ alterations in submandibular/sublingual function have the

greatest impact on the sensation of oral dryness.

Another useful technique for studying the salivary glands is lip

biopsy. The technique is a sensitive and specific diagnostic

procedure for Sjogren's syndrome. It is well tolerated and causes no

disfigurement. The changes in the minor glands of the lower lip show

a close correlation with those in the major salivary glands.\11\ In

addition to confirming the diagnosis, biopsy allows quantification

of the degree of lymphocytic infiltration and tissue damage.

Aggregates of lymphocytes within the acinar tissue are scored. An

aggregate of 50 or more cells represents a focus. The number of foci

within 4mm\2\ of glandular tissue is determined and constitutes the

focus score. A focus score of more than 1 is characteristic of

Sjogren's syndrome.\8\

Salivary scintigraphy, which measures the uptake, concentration,

and excretion of technetium pertechnetate by the major salivary

glands, is also a sensitive index of glandular function. However, it

is expensive, requires exposure to a radionuclide, and has little

advantage over the other two procedures.\8\

The symptoms of dry eyes and dry mouth in the absence of any

drug treatment or other disorder likely to be causal suggest a

diagnosis of Sjogren's syndrome.\11\ According to Talal\8\ the

diagnosis of Sjogren's syndrome is based upon the confirmed presence

of two of the following three criteria: (1) a focus score of more

than 1 in the labial salivary gland biopsy, (2) dry eye

(keratoconjunctivitis sicca), and (3) an associated connective

tissue or lymphoproliferative disorder. The triad of dry eyes, dry

mouth, and a connective tissue or collagen disease, usually

rheumatoid arthritis, is termed secondary Sjogren's syndrome.\11\

Dry eyes and dry mouth in the absence of a collagen disease is

referred to as primary Sjogren's syndrome. The use of diuretics,

anti-hypertensive drugs, antihistamines, antipsychotic, and

antidepressants may diminish lacrimal and salivary gland

function.\13\ Because the use of anticholinergic drugs as well as a

number of other medications may be the single most frequent cause of

xerostomia, it is essential to estsblish the presence of focal

lymphoid infiltrates and autoimmunity in a patient suspected of

having Sjogren's syndrome. Supportive serologic data would include

the presence of antinuclear antibodies, an elevated erythrocyte

sedimenation rate, and the presence of anti-SS-A and anti-SS-B

antibodies.

Treatment of xerostomia is difficult and includes preventing

caries, treating and retreating oral candidiasis, and attempting to

relieve the symptoms of dry mouth by increasing fluid intake,

replacing absent saliva with saliva substitutes, or stimulating the

remaining glandular tissue to secrete. Patients presenting with

milder stages of xerostomia may benefit from frequent small sips of

water or other fluids such as fruit nectars, and this may be as

effective as any other means of alleviating symptoms. Sialagogues

such as vitamin C tablets, sugarless chewing gum, mints, or hard

candies may offer temporary relief through masticatory or gustatory

stimulation. For other patients, saliva substitutes may ameliorate

symptoms and possibly increase salivary flow. Efforts at relieving

the symptoms of chronic xerostomia through the use of salivary

substitutes and by stimulating salivary flow usually offer only

temporary relief from dryness. Nevertheless, appropriate management

of patients with xerostomia requires that those patients whose

salivary flow can be increased by means of sialagogues be

distinguished from those patients whose salivary flow cannot be

stimulated, or whose flow is insufficiently stimulated.\14\ Patient

response can be tested with the use of a mechanical (paraffin

chewing) or a gustatory (citric acid) stimulant.\15\ The placement

of citric acid crystals or a 2% citric acid solution in the mouth

will stimulate demonstrable salivary flow within a few minutes in

responsive patients.\12\,\14\

Where stimulation of salivary flow by sialagogues has been

ineffective, saliva substitutes have been applied symptomatically to

alleviate mucosal discomfort and to air oral functioning.\10\

Artifical saliva substitutes usually contain carboxymethylcellulose

with or without the presence of natural mucins.

Carboxymethylcellulose is used to impart lubrication and viscosity.

Saliva substitutes that contain natural mucins maintain a surface

tension similar to that of natural salival. Salts are added to

artifical saliva to mimic the electrolyte content of natural

saliva.\15\ According to Brastings,\16\mucin-containing salivas are

preferred by patients because carboxy-methylcellulose compounds seem

to be uncomfortably sticky. Preparations containing mucin are

considered to provide formualtions that most closely resemble human

saliva.\17\ When applied using an atomizer, saliva substitutes wet

the oral cavity for about 30 minutes.\18\ In addition, intraoral

reserviors have been designed to allow continuous wetting of the

oral surfaces. Recently, a denture with a palatal reservoir for

artificial saliva has been constructed. The reservoir holds 2-3 cc

of substitute and needs to be refilled every 2-5 hours.\16\ Several

saliva substitutes are available and appear to be most successful

when used at night.\3\

Parasympathomimetic drugs have been used as pharmacologic

sialagogues in the treatment of xerostomia. Fox et al\4\

demonstrated that in persons with documented salivary gland disease

who have some functional salivary gland tissue, an orally

administered systemic agent is effective in relieving xerostomia and

increasing silivary output. Orally administered pilocarpine

increases the production of saliva by parotid and submandibular or

sublingual glands and relieves the sensation of oral dryness. The

investigators suggest that a sustained-release form of the drug may

offer increased therapeutic benefit. Scully\11\ recommends

pyridostigmine because it is longer acting with fewer side effects

than other pharmacologic agents. According to Vissink et at\14\ the

usefulness of pharmacologic sialagogues is limited because of their

side effects and contraindications.

By application of the concept of electrically stimulating nerves

to elicit a response, electrostimulation was developed for use in

the oral cavity to stimulate the salivary reflex. Investigators have

reported that electro-stimualtion increases salivary output and

should be used to treat patients with xerostomia secondary to

Sjogren's syndrome.\37\ The cost of a battery-operated, hand-held

stimulus probe that can provide electrical stimulation to the tongue

and hard palate is approximately $1,500.

Rationale

Proponents of electrostimulation as a method to increase

salivary production suggest that this procedure enhances the

patient's ability to generate saliva by augmenting normal

physiologic salivary reflexes. Salivary secretion is normally

controlled by reflex stimulation with effector nerve impulses

traveling along sympathetic as well as parasympathetic nerves to the

glands. Sympathetic nerve stimualtion produces a sparse viscous

secretion, whereas the parasympathetic nerve stimualtion produces a

voluminous watery secretion.\19\ The dual secretion (saliva) is a

flued mixture produced from paired major salivary glands (parotid,

submandibular, and sublingulal) and many smaller aggregations of

minor salivary glands imbedded in the submucosa of the cheeks, lips,

hard and soft palates, and tongue.

Proponents believe that xerostomia secondary to Sjogren's

syndrome can be caused by interruption of the stimulus that elicits

salivation at the effector site; such interruption results from loss

of glandular tissue with replacement by round cell infiltration,

scar, or fatty tissue. They postulate that an electronic device that

touches the tongue and roof of the mouth simultaneously will

stimulate tactile receptors, taste receptors, and intrinsic muscle

mechanoreceptors within the mucosa of the dorsum of the tongue and

the roof of the mouth. This produces electrical stimuation to the

oral and pharyngeal afferent nervous system resulting in a reflex

volley of efferent impulses to all residual salivary tissue, major

and minor, in the oral and pharyngeal regions causing salivation.

Review of Available Literature

It has long been known that the nerves to salivary glands

control the secretion of saliva. According to Garrett\19\ an

experiment in 1850 by Ludwig demonstraed that electrical stimulation

of the chordalingual nerve in the dog caused a copious secretion of

submandibular saliva.

In 1986 Weiss et al\7\ reported on the use of an electronic

stimulator as a mothod for increasing salivary production. In this

prelimianry investigation, 9 of the 24 patients with a primary

complaint of xerostomia had Sjogren's syndrome (diagnosed on the

basis of mdical history only). Following a visual examination of the

oral cavity as well as a gloved finger test to determine the

presence of moisture (any reflection was considered a sign of

wetness), patients were administered a 3-minute stimulus to the

tongue and roof of the mouth with the probe (electrodes) of the

hand-held stimulator. The maximum voltage delivered by the device is

6V with a current of 9 A. Patient tolerance controls and

determines the level of stimulation. Two subsequent stimulations of

3 minutes each were conducted at the same sitting by most of the

patients (actual numbers not reported). Each stimulation procedure

was followed by a subjective patient evaluation of improvement and a

repeat clinical examination.

According to the investigators, prior to stimulation, seven of

the nine patients with Sjogren's syndrome were considered to have

slight amounts of moisture present, and the remaining two patients

had ``no moisture'' present. Following stimulation, all nine

patients reported subjective impressions of increased salivation as

compared with prestimulation conditions. Clinical assessment was in

agreement with the subjective patient evaluations. Weiss et al.\7\

reported that the electronic device stimulates residual salivary

tissue in the oral and pharyngeal regions, producing increased

salivation.

In 1988, Steller et al.\3\ conducted a study of electrical

stimulation of salivary flow in patients with biopsy-proven

Sjogren's syndrome. The response to an electrical stimulus applied

to the tongue and hard palate was observed in a randomized, double-

blind, 4-week study of 29 subjects with xerostomia secondary to

Sjogren's syndrome. To be eligible to participate in the study,

subjects had to have an unstimulated whole (total gland secretions)

salivary flow rate of less than 0.2 g/min. Patients were randomly

assigned to active or placebo devices, which they used for 3

minutes, three times a day for 4 weeks. Response to stimulation was

assessed as whole saliva flow rates, which were measured at weeks 0,

2, and 4, both before and after stimulation with the device.

According to the investigators, there were no statistically

significant differences between changes in prestimulation whole

saliva flow rates or differences between the net changes in mean

whole saliva flow rate (poststimulation minus prestimulation flow)

of the active and placebo groups at each visit. The investigators

did find the changes in mean poststimulation whole saliva flow rates

between subjects using active and placebo devices from weeks 0 to 4

of the study to be statistically significant. However, analysis of

the results showed that the mean increase in the poststimulation

flow rate of the active device group (13 subjects) was due mainly to

the responses of three subjects who showed marked increases in their

whole saliva flow rates during the study. The investigators noted

that the initial salivary flow rates of these subjects were the

highest in that group, and their labial salivary gland focus scores

were among the lowest.

The investigators concluded that some Sjogren's syndrome

patients with residual salivary flow show significant responses to

electrical stimulation, but others with low or absent whole saliva

flow rates do not respond. During the 4-week study period no change

in the appearance of the oral mucosa was observed at the site of

electrode placement, and no marked changes or patterns of variation

in subjects' pulse and blood pressure were observed before or after

the device was used.

Discussion

Xerostomia is a complaint of elderly individuals, particularly

women.\6\ Decreases in both quantity of saliva as well as

composition cause a multitude of problems. In a healthy mouth,

copious saliva containing essential electrolytes, glycoproteins, and

antimicrobial enzymes continually lubricates and protects the oral

mucosa, thus cleaning the mouth, regulating acidity, maintaining the

integrity of the teeth, and destroying bacteria.

Currently, xerostomia is managed on the basis of subjective

symptoms, evidence of reduction in salivary flow, and complications

that result from dry mouth. To alleviate some of the problems

resulting from salivary dysfunction, pharmacologic sialagogues such

as pilocarpine and pyridostigmine as well as sialagogues that

include sugarless chewing gum, mints, or candy are prescribed in

order to stimulate more salivary flow.\18\ Sialagogues are effective

only if salivary gland function is present.

The preliminary investigation by Weiss et al.\7\ in 1986

demonstrated that a probe providing electrical stimulation applied

to the tongue and hard palate of patients with xerostomia presumed

secondary of Sjogren's syndrome produces a salivary response. The

salivary response was obtained in the nine patients following a

single session of one to three electrical stimulations of 3 minutes

each. As a preliminary investigation, this study did not include a

control group or any quantitative assessment of salivary response,

duration of response, or long-term assessment of efficacy. Moreover,

seven of the nine patients tested exhibited residual saliva

production prior to treatment and may have been exhibiting a tactile

response to the probe.

The only other published report determining whether an

electrical stimulus applied to the tongue and hard palate could

stimulate salivary flow in subjects with xerostomia secondary to

Sjogren's syndrome is the randomized, double-blind, 4-week study

reported by Steller et al. in 1988.\3\ The results of this short-

term study indicate that some Sjogren's patients with residual

salivary flow in an unstimulated state (<0.11-0.20 g/2 min) show a

significant response to electrical stimulation, but others with low

(less than 0.11 g/2 min) or absent whole saliva rates do not respond

or respond to a clinically insignificant degree. Only 3 of 13

patients using the active device showed a significant response

(about 0.6-1.0 g/2 min) in salivary production when compared with

the responses of the placebo group. The whole saliva flow rates of

the remaining 10 subjects in the active group remained below 0.25 g/

2 min throughout the study and were not of the order of magnitude

necessary to indicate a significant salivary response. Whole saliva

flow rates of 10 subjects in the placebo group remained below 0.20

g/2 min throughout the study. It appears that additional studies

with larger patient populations are needed to define specific

degrees of salivary function or dysfunction that would respond to

electrical stimulation. These studies could help to determine

whether a single salivary response to electro-stimulation or some

other test such as lip biopsy focus score should be used to help

identify those patients who may benefit from the technique.

Guidelines that would specify which types of Sjogren's patients

with what degree of xerostomia and at what points in their clinical

evaluation or management would benefit from electrostimulation

cannot be developed without further clinical investigation. Long-

term studies of well-characterized patient groups will also help to

determine how long it takes to achieve a response. According to some

investigators, this should allow sufficient time to determine if any

regeneration of the salivary gland parenchyma is achieved. In order

to determine the effectiveness of electrical stimulation of salivary

flow in Sjogren's patients, studies should include information

regarding concomitant therapy (continued frequent water sipping or

use of other sialagogues) and the duration of the salivary response

so that it can be compared with the use of other therapies. Studies

and subsequent management of Sjogren's patients with dry mouth

should include quantitative assessment of salivary function

(unstimulated and stimulated, whole and individual gland salivas),

assessment of oral conditions for signs of salivary hypofunction,

and subjective patient evaluations.

Salivary glands in patients who suffer from rheumatoid diseases

show varying degrees of destruction. This damage is progressive and

considered irreversible by some investigators.\17\ The ability to

induce secretion in individuals with these conditions will be

inversely related to the glandular damage. The study by Stellar et

al\3\ shows that a device providing electrical stimulation to treat

dry mouth in patients with Sjogren's syndrome appears to be

effective after 4 weeks of study in only a small percentage of

patients. These patients may represent a group with less advanced

disease (lesser degree of lymphocytic infiltration) and a greater

amount of functional salivary parenchyma. These individuals would

likely respond equally well to mechanical, chemical, tactile, and

pharmacologic means of salivary stimulation. Anything that enhances

mastication will induce secretion. So, too, will salts and citric

acid solutions. While all of these techniques are effective, their

effects are transient; however, there have been no studies to

demonstrate that electrical stimulation provides any advantage or is

more effective than other existing techniques.

Successful treatment for dry mouth is recorded as both

subjective and objective increases in saliva output. According to

Fox et al,\5\ patient complaints of xerostomia or oral dryness may

not reflect actual salivary gland capabilities or function.

Subjective assessments alone are not adequate for diagnostic or

therapeutic purposes. Although there is no fixed salivary level for

intervention, xerostomia is generally associated with whole saliva

flow rates of less than 0.1 mL/min. For some patients, a 50%

reduction in salivary output leads to the subjective impression of

dry mouth. However, the level of diminished salivary output where a

patient becomes subject to increased risk of oral disease or

dysfunction is not known. Moreover, there is a wide variability of

``normal'' salivary output. A 50% decline for one individual might

still result in a flow rate greater than another individual's normal

output. Some investigators feel that if the minor salivary glands

can be stimulated to coat the mucosa with a thin layer of mucous,

the sensation of dryness will be relieved. Even very small increases

in saliva output may be beneficial in preventing or minimizing the

oral effects of salivary dysfunction. Long-term clinical studies are

needed to examine these issues.

Consultations

According to the National Institutes of Health (NIH),

electrostimulation may be useful in management of salivary

hypofunction, but adequate data for definitive conclusions are not

available. Electrostimulation is not widely accepted as an effective

method of treating xerostomia secondary to Sjogren's syndrome. In

addition, the number of published studies is limited.

NIH has informed OHTA that guidelines that specify which types

of xerostomic patients with which conditions and at what points in

their clinical evaluation and/or management would benefit from

electrostimulation cannot be developed without further clinical

studies utilizing well-characterized patient populations. Given the

single published study showing that only patients with residual

salivary flow in an unstimulated state will respond to

electrostimulation, NIH suspects that those individuals would likely

respond as well to other means of salivary stimulation, including

gustatory or masticatory stimuli. NIH has expressed doubt as to

whether electrostimulation using a limited stimulus time (3 minutes,

three times a day) could provide sufficient duration of increased

salivary output to have a significant impact on the oral health or

symptoms of the patient.

The Food and Drug Administration (FDA) has informed OHTA that in

May 1988 a manufacturer received premarket approval for a salivation

electrostimulator device based upon submission\20\ of engineering,

preclinical, and clinical studies and the recommendation of the

Dental Devices Panel, FDA's Center for Devices and Radiological

Health. The short-term double-blind clinical study of the device was

conducted at three institutions and included 40 patients using an

active device and 37 patients assigned a placebo. The work by

Steller et al\3\ discussed in the literature review section is part

of this submission. Based on the data submitted, the FDA found an

increase in saliva production from the patient group using the

active device compared with the patient group using the placebo

device. Subjective improvement of a burning sensation of the tongue

was noted by 12 of 22 patients treated with the active device, and

an improvement in the ability to swallow was reported by 13 of these

patients.

The manufacturer provided the FDA with a long-term clinical

study of 34 patients with Sjogren's syndrome and xerostomia that was

intended to follow patients for up to 12 months. Patients were

assessed by the physician for moisture (oral examination) prior to

the study and at visits on 1, 3, 6, and 12 months following

stimulation. Eleven of 12 patients who completed 12 months of

electrical stimulation were found on the last visit to have a

discernible improvement in salivary status when compared with the

initial assessment. As a followup to this study, a group of 23

patients was surveyed by the manufacturer via telephone to assess

changes in quality of life after using electrical stimulation for 6-

18 months. Patients indicated improvement that included increased

ease of swallowing and improved dental checkups as well as education

in burning tongue sensation, sleep interruptions, and water intake.

This device is indicated for use in patients with xerostomia

secondary to Sjogren's syndrome and intended to stimulate salivary

production from existing glandular tissue. Patients who show an

initial response to electrostimulation are considered to be

candidates for this therapy. According to the FDA there are no

contraindications associated with the use of this device.

Medical Specialty and Clinician Responses

Medical specialty groups such as The American Dental Association

were unable to provide any information regarding the

electrostimulation of salivary glands.

Comments from clinicians with knowledge of or experience with

electrical stimulation of salivary production are equivocal. Some

expressed the opinion that electrostimulation is a safe and

effective method for the treatment of xerostomia secondary to

Sjogren's syndrome. Others suggested that the method has been

inadequately tested. Some clinicians recommended beginning

electrical stimulation of the salivary glands in patients with

Sjogren's syndrome and dry mouth early in the course of the disease

in order to possibly prevent, modify, or even reverse the

progression of a salivary gland atrophy. Other clinicians are not

convinced that electrostimulation is more effective than other

simple, less costly stimulation techniques such as gustatory

stimulation or intraoral tactile stimulation.

Summary

Electrostimulation has been introduced as a technique for

increasing salivary output in the treatment of patients with

xerostomia (dry mouth) secondary to Sjogren's syndrome. The

procedure uses an electrostimulation device (salivation

electrostimulator) to increase salivary production from existing

glandular tissue. The device delivers a low-voltage electrical

stimulus to the mouth via a probe. Patients with residual salivary

tissue in the oral and pharyngeal regions who demonstrate a decrease

in the flow rate of saliva are potential candidates for this

procedure.

It is estimated that more than one million people in the United

States, predominantly middle-aged and elderly women, suffer from

Sjogren's syndrome. Patients with chronic xerostomia complain of a

continual feeling of oral dryness and have difficulty eating dry

foods. These patients are susceptible to increased caries, oral

pain, infection, and have difficulty speaking, chewing, and

swallowing.

The approach to the treatment of xerostomia in Sjogren's

patients is usually determined by the level of severity of the

symptoms. Appropriate management of patients with xerostomia

requires that those patients whose salivary flow can be increased by

means of sialagogues be distinguished from those patients whose

salivary flow is either unaffected or insufficiently stimulated. To

alleviate some of the complications due to salivary dysfunction in

those patients who respond to stimuli, pharmocologic sialagogues as

well as sialagogues that include sugarless gums, mints and candies

are prescribed in order to increase salivary flow.

Recently, electrostimulation via a hand-held stimulus probe has

been introduced as a method of treatment in xerostomia secondary to

Sjogren's syndrome. From the single published study as well as data

provided to the FDA, it appears that an electrical stimulus applied

to the tongue and hard palate (by a battery-operated device) may be

useful in the management of salivary hypofunction in certain

patients. It appears, however, that there are insufficient data at

the present time to determine the clinical utility of

electrostimulation, to evaluate the long-term clinical effectiveness

of this modality of salivary production, or to identify those

xerostomic patients who would benefit from this procedure. Also,

electrostimulation is not widely accepted as an effective method of

treatment for xerostomia secondary to Sjogren's syndrome. The number

of published studies is limited and other less expensive treatments

are available. Further research of electrical stimulation of

salivary flow is required to determine its role in the treatment of

Sjogren's patients with xerostomia.

References

1. Arthritis Medical Information Series: Sjogren's Syndrome.

Atlanta: Arthritis Foundation, 1988.

2. Peterson JK. Xerostomia. Scand J. Rheumatol 1986;61(suppl):185--

189.

3. Steller M, Chou L, Daniels TE. Electrical stimulation of salivary

flow in patients with Sjogren's syndrome. J Dent Res.

1988;67(60):1334--1337.

4. Fox PC, Baum BJ, Mandel ID. Pilocarpine for the treatmnt of

xerostomia associated with salivary gland dysfunction. Oral Surg

1986;61(3):243--248.

5. Fox PC, van der Ven PF, Sonies BC, et al. Xerostomia: Evaluation

of a symptom with increasing significance. J Am Dent Assoc.

1985;110:519--525.

6. Rhodus NL. Xerostomia: An increasingly significant dental

management challenge. Northwest Dentistry 1987;66(4):14-18.

7. Weiss WW, Brennan HS, Katz P, et al. Use of electronic stimulator

for the treatment of dry mouth, J Oral Maxilo-fac Surg 1986;41:845--

850.

8. Talal N. Sjogren's syndrome, in Wyngaarden JB, Smith LH (Eds):

Cecil Textbook of Medicine (17th ed). Philadelphia: Saunders, 1985,

pp. 1936--1937.

9. Whaley K, Alspaugh MA. Sjogren's syndome, in Kelly WN, Harris ED,

Ruddy s, et al(Eds): Textbook of Rheumatology (vol 1). Philadelphia:

Saunders, 1985, pp. 956--973.

10. Weerkamp AH, Wagner K, Vissinic A, et al. Effect of the

application of a mucin-based saliva substitute on the oral

microflora of xerostomic patients. Oral Pathol 1987;16(9):474--478.

11. Scully C. Sjogren's syndrome: Clinical and laboratory features,

immunopathogenesis, and management. Oral surg 1986;62(5):510--523.

12. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomic and

objective measures of salivary gland performance. J Am Dent Assoc

1987;115:581--584.

13. Talal N. Overview of Sjogren's syndrome. J Dent Res

1987;66(special issue): 672--674.

14. Vissink A, Johannes's-Gravenmade E, Panders AK, et al. Treatment

of Hyposalivation. Ear Nose Throat J 1988;67:179--185.

15. Levine MJ, Aquirre A, Hatton MN, et al. Artificial salivas:

Present and future. J Dent Res 1987;66:693--698.

16. Brastings ED. Saliva, xerostomia, and salivary substitutes. Pa

Dent J 1987;54(5):23--24.

17. Duxbury AJH, Thakker NS, Wastell DG. A double-blind cross-over

trial of a mucin-containing artificial saliva. Br Dent J

1989;166:115--120.

18. Vissink KA, Panders AK,'sGravenmade EJ, et al. Treatment of oral

symptoms in Sjogren's syndrome. Scand J Rheumatol

1986;61(suppl):270--273.

19. Garrett JR. The proper role of nerves in salivary secretion: A

review. J Dent Res 1987;66(2):387--397.

20. Food and Drug Administration. Summary of Safety and

Effectiveness Data: Salivation Electro-Stimulation Device,

(unpublished report), 1988.

[FR Doc. 94-12457 Filed 5-20-94; 8:45 am]

BILLING CODE 4121-01-P