Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia. MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected. RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003). CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates. CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

World Workshop on Oral Medicine VI: clinical implications of medication-induced salivary gland dysfunction.

OBJECTIVE: This study aimed to systematically review the available literature on the clinical implications of medication-induced salivary gland dysfunction (MISGD). STUDY DESIGN: The systematic review was performed using PubMed, Embase, and Web of Science (through June 2013). Studies were assessed for degree of relevance and strength of evidence, based on whether clinical implications of MISGD were the primary study outcomes, as well as on the appropriateness of study design and sample size. RESULTS: For most purported xerogenic medications, xerostomia was the most frequent adverse effect. In the majority of the 129 reviewed papers, it was not documented whether xerostomia was accompanied by decreased salivary flow. Incidence and prevalence of medication-induced xerostomia varied widely and was often associated with number and dose of medications. Xerostomia was most frequently reported to be mild-to-moderate in severity. Its onset occurred usually in the first weeks of treatment. There was selected evidence that medication-induced xerostomia occurs more frequently in women and older adults and that MISGD may be associated with other clinical implications, such as caries or oral mucosal alterations. CONCLUSIONS: The systematic review showed that MISGD constitutes a significant burden in many patients and may be associated with important negative implications for oral health.

Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial.

OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.

Established and novel approaches for the management of hyposalivation and xerostomia.

Hyposalivation, often symptomatically manifested as xerostomia (dry mouth sensation) may indicate the presence of altered salivary gland function and places patients at a higher risk for oral complications. Diverse symptoms and consequences have been associated with hyposalivation, such as difficulties with speaking, swallowing and tasting and a significant increase in dental caries and other oral infections. Although hyposalivation may be caused by a variety of conditions (head and neck radiotherapy, Sjogren's syndrome, medications, etc.), its hallmark symptom, xerostomia, is common to all such disorders, and varies only in intensity. Therefore, treatment is generally non-specific, and similar therapeutic approaches are used in all cases. In the present paper, available palliative oral care in the form of saliva substitutes, such as mouthwashes or gels, is detailed. Also salivary flow stimulants, such as certain pharmaceutical or gustatory preparations, acupuncture and electrostimulation are reviewed. Finally, other approaches, currently under investigation, such as biological and gene therapies, are discussed. The degree of evidence of the best known methods and their intended use are analyzed.

Electroestimulación, una alternativa para el manejo de la hiposalivación y la xerostomía / Electrostimulation, an alternative to the management of hyposalivation and xerostomia

Se presenta el uso de la electroestimulación por medio de un dispositivo intraoral removible, como una alternativa para el manejo de la hiposalivación y la xerostomía. El dispositivo emite una corriente eléctrica suave, no percibida por elusuario, hacia la mucosa oral en el lado lingual de la zona del tercer molar inferior. Esa corriente excita el nervio lingual. Como consecuencia, por un lado son estimuladas las glándulas submandibular y sublingual, inervadas por las fibras eferentes del nervio lingual y por el otro, el reflejo salivatorio por medio de las fibras eferentes del mismo nervio. Una serie de experimentos clínicos han confirmado el efecto clínico positivo del dispositivo, tanto a nivel subjetivo del paciente como en lo referente a la secreción salival.

[Electrostimulation for the treatment of dry mouth].

Xerostomia is a very common condition, which not only involves dry mouth feeling, but can also lead to psychosocial distress, impaired quality of life, and complications, such as dental caries and oral candidiasis. It is generally induced by hypofunction of salivary glands, which has a wide variety of etiologies, such as Sjögren's syndrome, radiotherapy to the head and neck and side effects of medications. Current therapies rely on saliva substitutes and pharmacological stimulation of the parasympathetic system. These treatment modalities are somewhat limited by their short-term efficacy, high cost and drug interactions or other adverse effects. Local transcutaneous or permucosal electrostimulation in areas close to the nerves participating in the salivary autonomic reflex has been found to increase salivary secretion in animal and clinical experiments and to relieve symptoms of dry mouth in patients with salivary gland hypofunction. This concept is reviewed to update the readers on the current status and potential of intraoral miniature electrostimulating devices. They offer promise as an optional safe and non-chemical treatment of xerostomia.

Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: a trial on pigs.

Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5 min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 min, followed by a slow decrease. After 6h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.

Association between salivary flow rates, oral symptoms, and oral mucosal status.

OBJECTIVE: To investigate the association of salivary flow rates with oral symptoms and oral mucosal status. STUDY DESIGN: The study population included 462 Israeli subjects attending a xerostomia clinic. After patient history and oral mucosal examination, major gland sialometry, and complementary tests, patients were divided into 6 groups: drug-induced salivary gland hypofunction (SGH), Sjögren syndrome (SS), radiation-induced SGH, idiopathic SGH, xerostomia without SGH, and control. RESULTS: Oral mucosal alterations were more prevalent in all SGH groups than in the control group. Oral symptoms (except speech impairment) were more frequent in all SGH groups. The postradiation group showed the highest frequency of oral mucosal alterations and of swallowing and mastication complaints. Individuals complaining of xerostomia (compared with those who did not) displayed lower major salivary gland flow rates and a higher frequency of oral mucosal alterations CONCLUSIONS: Presence of oral mucosal alterations may help but are not enough to identify patients for further evaluation of SGH. Difficulties in mastication and swallowing are most specifically related to advanced SGH.

Major salivary gland output differs between users and non-users of specific medication categories.

BACKGROUND: The intake of medications is a major aetiologic factor of xerostomia. The purpose of this study was to investigate the selective influence of medication categories on flow rates of individual major salivary glands. METHODS: The effect of each medication category on salivary flow rates was determined by dichotomy comparisons between users and non-users. A total of 246 patients were included, 79 males and 167 females aged 13-92 years (mean 63 years). Of these, 200 used medications, which were grouped according to their category. A comprehensive medical and oral examination was performed. Both unstimulated and stimulated saliva was collected separately from the parotid and submandibular/sublingual glands. RESULTS: Parotid flow rate was decreased among users of tranquillisers and sedatives (unstimulated flow), cardiovascular drugs and gastrointestinal drugs (stimulated flow). Submandibular/sublingual unstimulated output was lower in patients taking cardiovascular drugs, antihistamines, tranquillisers/sedatives and antidepressants, while the stimulated flow, in those taking cardiovascular drugs, antihistamines, tranquillisers/sedatives and gastrointestinal drugs. CONCLUSIONS: Users of many common medication categories display significantly reduced unstimulated and/or stimulated salivary flow rate from the major salivary glands compared with non-users. A larger number of medication categories are associated with reductions in salivary flow rate from submandibular/sublingual glands than parotid glands.

A simple technique for the determination of salivary gland hypofunction.

OBJECTIVE: Present volumetric or gravimetric techniques for measuring saliva output are often cumbersome and, therefore, not generally used. In the present study, a simple approach to study the weight loss of a standard hard sugar candy after 3 minutes of passive incubation between tongue dorsum and palate was tested. STUDY DESIGN: Subjects (n = 59), 27 of whom had a subjective complaint of dry mouth and the rest who were healthy control subjects, were tested with this procedure, together with gravimetric measurements of stimulated and unstimulated saliva output from various glands (parotid, submandibular, and sublingual). Correlations between a decrease in candy weight and salivary flow rate were determined for the 2 groups of subjects, taken separately, as well as for the entire subject population, by using the Pearson product moment correlation. RESULTS: In most cases, highly significant associations were found, particularly when comparing candy weight loss with stimulated parotid and submandibular and sublingual saliva. Data were submitted to dichotomous analysis and divided according to salivary flow rate by using a cutoff 0.23 g for candy loss; the sensitivity, specificity, and positive predictive values were 92%, 85%, and 82%, respectively. CONCLUSIONS: The candy weight-loss test is a simple, rapid measure of salivary hypofunction, which correlates with saliva output and reports of subjective dry mouth.

Submandibular and sublingual salivary gland function in familial dysautonomia.

OBJECTIVE: Drooling in familial dysautonomia (FD) has been attributed to denervation supersensitivity. The aim of this study was to investigate submandibular and sublingual (SM/SL) gland function in FD. STUDY DESIGN: SM/SL saliva was collected from 15 children with FD and from 31 healthy control subjects. The protein and electrolyte content and the salivary flow rate were determined in each subject. RESULTS: Children with FD displayed significantly elevated outputs of chloride, potassium, calcium, phosphorous, magnesium, and total protein. Salivary flow rates were significantly increased. Phosphorous concentration was statistically low. These results imply SM/SL hyperfunction at the acinar and ductal levels. The concentration of lysozyme, the activity of amylase, and the output of both were similar in patients and control subjects. CONCLUSION: SM/SL gland hyperactivity is a newly described abnormality in FD. At the acinar level, this hyperactivity is expressed with increased fluid, electrolyte, and protein output, and at the ductal level, with increased ion secretion and absorption rate. These changes may be the result of ongoing parasympathetic denervation characteristic in FD.

Oral surgery in patients on anticoagulant therapy.

OBJECTIVE: Surgery is the main oral healthcare hazard to the patient with a bleeding tendency, which is mostly caused by the use of anticoagulants. The traditional management entails the interruption of anticoagulant therapy for dental surgery to prevent hemorrhage. However, this practice may increase the risk of a potentially life-threatening thromboembolism. Because this issue is still controversial, it is the aim of this paper to review the evidence, to highlight the areas of major concern, and to suggest management regimens for patients on the 3 main types of anticoagulants: coumarins, heparins, and aspirin. MATERIALS REVIEWED: The pertinent literature and clinical protocols of hospital dentistry departments have been extensively reviewed and discussed. RESULTS: Several evolving clinical practices in the last years have been detected: anticoagulant use is generally not discontinued; oral surgery is performed despite laboratory values showing significant bleeding tendency; new effective local methods are used to prevent bleeding; and patients at risk are referred to hospital-based clinics. CONCLUSION: The management of oral surgery procedures on patients treated with anticoagulants should be influenced by several factors: extent and urgency of surgery, laboratory values, treating physician's recommendation, available facilities, dentist expertise, and patient's oral, medical, and general condition.