Effectiveness of Mandibular Advancement Appliances in Treating Obstructive Sleep Apnea Syndrome: A Systematic Review

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1 The Laryngoscope VC 2015 The American Laryngological, Rhinological and Otological Society, Inc. Systematic Review Effectiveness of Mandibular Advancement Appliances in Treating Obstructive Sleep Apnea Syndrome: A Systematic Review Sara Serra-Torres, DDS; Carlos Bellot-Arcıs, DDS, PhD; Jose M. Montiel-Company, DDS, MD, PhD; Jaime Marco-Algarra, MD, PhD; Jose M. Almerich-Silla, MD, PhD Objectives/ypothesis: Mandibular advancement devices are an alternative to continuous positive airway pressure for patients with mild or moderate obstructive sleep apnea/hypopnea syndrome (OSAS). The main aim of this review was to assess the effectiveness of different devices in treating OSAS, based on polysomnographic measurements such as the apnea/ hypopnea index (AI) and oxygen saturation, and on changes in the upper airway and improvements in the most common symptoms: snoring and somnolence. Their adverse effects were also noted. Study Design: Systematic review. Methods: Following an exhaustive search in the Medline, Scopus, and Cochrane Library databases, 22 articles published in the past 10 years met the quality and inclusion criteria. Results: Using mandibular advancement devices during the hours of sleep helps to prevent snoring and excessive daytime sleepiness, reduce the AI significantly, and bring about beneficial changes in the upper airway. Adjustable and custommade mandibular advancement devices give better results than fixed and prefabricated appliances. Monobloc devices give rise to more adverse events, although these are generally mild and transient. Conclusions: Mandibular advancement devices increase the area of the airway. They bring the soft palate, tongue, and hyoid bone forward and activate the masseter and submental muscles, preventing closure. All these effects reduce the AI, increase the oxygen saturation, and improve the main symptoms of OSAS. Key Words: Obstructive sleep apnea, mandibular advancement splints, mandibular advancement appliance, mandibular advancement device. Level of Evidence: NA Laryngoscope, 126: , 2016 INTRODUCTION Obstructive sleep apnea/hypopnea syndrome (OSAS) is a respiratory sleep disorder, listed in the International Classification of Sleep Disorders, that consists of recurrent episodes of total or partial blockage of the passage of air. 1 It occurs because an anatomical or functional narrowing of the upper airway can lead to its closure, causing decreased oxyhemoglobin saturation and repeated miniawakenings that give rise to daytime sleepiness and to neuropsychiatric, respiratory, and cardiac disorders. 2 5 It is the most common respiratory disorder to be recognized as a serious public health problem. 4 Itaffects4%to6%ofmenand2%to4% of women, with higher incidences in obese persons. 3 OSAS From the Stomatology Department (S.S.-T., C.B.-A., J.M.M.-C., J.M.A.-S.); and Otorhinolaryngology Unit, University Clinical ospital (J.M.-A.), Faculty of Medicine and Dentistry, University of Valencia, Valencia, Spain. Editor s Note: This Manuscript was accepted for publication June 18, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Carlos Bellot-Arcıs, Departamento de Estomatologıa, Unidad docente de Preventiva, Clınica Odontologica, C/ Gasco Oliag No. 1, CP: 46010, Valencia, Spain. bellot.arcis@ gmail.com DOI: /lary is classified by the number of pauses in breathing per hour of sleep (the apnea/hypopnea index [AI]) as mild (AI ), moderate (AI ), or severe (AI > 30). 3 The symptoms occur both at night and during the day. The most common are snoring, asphyxial episodes, abnormal movements, diaphoresis, frequent awakenings, nightmares, restless sleep, insomnia, dribbling, bruxism, dry mouth, night sweats, excessive daytime sleepiness, chronic tiredness, morning headaches, irritability, depression, and difficulty in concentrating. Excessive daytime sleepiness, measured by subjective methods such as the Epworth Sleepiness Scale (ESS), is the most prevalent daytime symptom. 6 The method of choice for diagnosing OSAS is polysomnography, which assesses the quantity and quality of sleep and identifies the different respiratory events. 6 Part of the treatment consists of changing dietary habits, cutting out alcohol and tobacco, and sleeping in a different position. 6 Although surgical procedures such as maxillomandibular advancement or uvulopalatopharyngoplasty are available, 2 continuous positive airway pressure (CPAP) is the treatment of choice for OSAS. CPAP increases the area of the upper airway, preventing it from closing, 4,7,8 but it is very uncomfortable for the patient and presents numerous adverse effects such as nasal congestion and dryness of the mucosa

2 Fig. 1. Flow diagram. AI 5 apnea/ hypopnea index; MAD 5 mandibular advancement device. [Color figure can be viewed in the online issue, which is available at A noninvasive alternative is to use oral mandibular advancement devices (MADs). 9,10 Although less effective than CPAP, they present fewer side effects, better tolerance, and greater personal satisfaction. Although some authors consider that their use should be limited to mild and moderate OSAS, 12,16,17 others also advocate this treatment for severe OSAS cases A systematic review by Lim et al. 22 concluded that MADs would be an appropriate recommendation for patients with mild OSAS symptoms and for those who had difficulty in tolerating CPAP. MADs are classified as adjustable when they contain a mechanism by which to increase the degree of mandibular advancement, or fixed when they are manufactured in a fixed position (generally between 60% and 80% of maximum mandibular protrusion). They can be prefabricated or custom made 23 and can also be monobloc or duobloc, depending on whether the MAD is composed of one or two pieces. 24 The purpose of this review was to examine the scientific evidence concerning the effectiveness of MADs in treating OSAS. The objectives of the systematic review were: 1) to assess the effectiveness of different MADs in treating OSAS, based on the main objective polysomnographic measurements, such as AI and oxygen saturation, as well as on changes in the upper airway and 508 improvements in symptoms such as snoring and daytime sleepiness; and 2) to assess the most frequent adverse effects in relation to the use of MADs. MATERIALS AND METODS A systematic review of the bibliography was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations and CONSORT criteria. 25 Study Selection Criteria The selection criteria for the articles to be included in the review were as follows. The article types accepted were articles, articles in press, and reviews concerning studies conducted in adults. Only the following types of study were accepted: systematic reviews and meta-analyses, randomized clinical trials, cohort studies, and case control studies, both prospective and retrospective. All such studies of treating OSAS with different MADs were included. Search Strategy and Screening of Articles To identify the relevant studies, irrespective of language, a detailed electronic search was carried out in the Medline, Scopus, and Cochrane Library databases. All studies published between 2004 and 2014 were included.

3 TABLE I. Effectiveness of Different Types of MAD by Sleep AI and Oxygen Saturation. Study Type of Follow-up Time, Study No. and Type of MAD BMI, kg/m 22 mo (Losses) AI Oxygen Saturation I, e/h; F, e/h % Reduction Initial Final Q Tsuiki P 20 adjustable duobloc* (0) I: ; F: % 72.2% % % M Lawton P 16 fixed duobloc 1 adjustable duobloc (0) I: 45.5; F: adjustable duobloc, 24.5; fixed duobloc, 34 Custom-made adjustable duobloc, 46.15%; fixed duobloc, 25.27% 87.5% erbst, 89%; Twin Block, 88% Itzhaki PC (4) I: ; F: % adjustable duobloc Giannasi P 29 adjustable (0) I: ; F: % 98.1% 6 1.4% 98.7% 6 0.6% Vanderveken P 35 prefabricated (0) I: ; F: cm, 6 6 8; tp, cm, 57.14% ; tp, 95% 6 1% cm, 95% 6 1%; 21.42% tp, 95% 6 2% Poon P 14 thermoplastic 1 (4) I: ; F: % 75.5% % 86% 6 8.4% adjustable duobloc Ghazal P 103 thermoplastic adjustable or adjustable (58) I: IST, 23; TAP, 21; F: IST, 8.7; TAP, 5.3 IST, 62.17% ; IST, 82; TAP, 82 IST, 85.5; TAP, 86 M TAP, 74.76% Kurtulmus P 10 moderate OSAS 1 10 mild OSAS, fixed MAD (10) I: mild, ; mod., ; F: mild, ; mod., Mild, 74.31% ; mod., 64.51% Chan P (0) I: ; F: % adjustable duobloc Aarab P 20 adjustable, 25%, 50%, & 75% protrusion (3) I: ; F: 25%, ; 50%, ; 75%, %, 53.47% ; 50%, 67.39% ; 75%, 74.78% ; Lettieri R 922 fixed and adjustable adjustable, fixed 84 (117) I: fixed, ; adjustable, ; F: fixed, ; adjustable, Fixed, 66.77% ; Fixed, 83.3% 6 adjustable, 74.41% 8.8%; adjustable: 83.8% 6 7.6% Fixed, 85.7% 6 6.5%; adjustable, 88.1% 6 7.2% Duarte P 15 adjustable (0) I: 18.3; F: % Zhou & Llu P 16 adjustable monobloc 1 adjustable duobloc (0) I: ; F: monobloc, ; SILENT NITE, Monobloc, 71.26% ; SILENT NITE, 66.37% De Lima P 30 adjustable (10) I: ; F: % Dieltjens P (4) I: ; F: % adjustable Gasparini P 18 Gasparini 29 6 (0) I: 31.5; F: % 78% 90% M Giannasi P (8) 56 OSAS; I: adjustable ; F: % 97.5% 6 1.8% 97.7% 6 2.2% Banhiran P 64 prefabricated (4) I: ; F: % 94.7% 6 2.0% 96.2% 6 1.6% adjustable AI classification: mild (AI ), moderate (AI ), severe (AI > 30; Lawton et al. 3 ). The success criteria considered were a 50% reduction in AI or a change in AI level from severe or moderate to mild OSAS. *Klearway. P <.05. Twin Block. erbst. Adjustable PM Positioner. # VR IST : Modified erbst appliance. k TAP. SomnoDent. **SILENT NITE. RespiDent Butterfly. Gasparini et al. 24 Somnoguard AP. AI 5 apnea/hypopnea index; BMI 5 body mass index; cm 5 ; e/h 5 apnea/hypopnea events/hour; F 5 final; 5 high; I 5 initial; M 5 medium; MAD 5 mandibular advancement device; mod.- 5 moderate; OSAS 5 obstructive sleep apnea/hypopnea syndrome; P 5 prospective study; PC 5 prospective controlled study; Q 5 quality; R 5 retrospective study; TAP 5 Thornton Adjustable Positioner; tp 5 prefabricated. 509

4 TABLE II. Effectiveness of Different Types of MAD by Velopharynx Size and Decrease in Snoring and Daytime Sleepiness. Study Type of Follow-up Study No. and Type of MAD BMI, kg/m # Time, mo (Losses) Velopharynx Size Snoring & Sleepiness Initial Final Q Tsuiki P 20 Klearway (0) Velopharynx increased, anterior wall curvature reduced Lawton P 16 Twin Block 1 erbst (0) Sleepiness: VAS, 3.0; ESS, 10.0; snores/hr: Snoring & sleepiness ceased Sleepiness: VAS, erbst, 2.0; Twin Block, 2.5*; ESS, erbst, 8.0; Twin Block, 8.5; snores/hr: erbst, 64.0; Twin Block, 88.0 Itzhaki PC 16 erbst (4) ESS: ESS: * Giannasi P (0) Snoring decreased adjustable M Vanderveken P 35 prefabricated monobloc 1 Poon P 14 thermoplastic adjustable duobloc Ghazal P 103 thermoplastic adjustable or adjustable (0) Snoring: VAS, 8 6 2; ESS, (4) Nasopharynx: initial, ; final, Snoring: VAS, cm, 2 6 3*; tp, 4 6 3*; ESS, cm, 5 6 4; tp, (58) ESS: IST, 7.5; TAP, 10.0 ESS: IST, 6.5*; TAP, 4.5* M Chan P (0) Transverse: 140% 6 adjustable duobloc # 10%; lateral: 125% 6 5%; anteroposterior: 17% 6 6% Duarte P 15 adjustable (0) ESS: 9.5 ESS: 4.2* Zhou & Llu P adjustable monobloc 1 adjustable duobloc # (0) UA space increased ESS: ESS: monobloc, *; SILENT NITE, * Dieltjens P (4) ESS: ; snoring: adjustable # VAS, ESS: 7 6 4*; snoring: VAS, 3 6 2* Giannasi P (8) ESS: 13.0 ESS: 8.5* adjustable Brown P 30 prefabricated M fixed nylon # (2) Lateral dimension of UA increased Banhiran P 64 prefabricated (4) ESS: ESS: * adjustable *P <.05. Adjustable PM Positioner. IST VR : Modified erbst appliance. TAP; # SomnoDent. k SILENT NITE. RespiDent Butterfly. **Elastoplast Sport. BMI 5 body mass index; cm 5 ; ESS 5 Epworth Sleepiness Scale; 5 high; M 5 medium; MAD 5 mandibular advancement device; P 5 prospective study; PC 5 prospective controlled study; Q 5 quality; TAP 5 Thornton Adjustable Positioner; tp 5 prefabricated; UA 5 upper airway; VAS 5 visual analogue scale. 510

5 TABLE III. Adverse Effects and Changes as a Result of Using MADs. Author Type of Study No. and Type of MAD BMI, kg/m 22 Follow-up Time, mo (Losses) Adverse Effects Q Lawton P 16 Twin Block 1 erbst (0) Short term (2 3 days) vs. long term (1 1.5 months); erbst: muscular discomfort, 56% vs. 25%; TMJ discomfort, 69% vs. 31%; dry mouth: 63% vs. 56%; excessive salivation, 31% vs. 19%; Twin Block: muscular discomfort, 50% vs. 19%; TMJ discomfort, 38% vs. 19%; dry mouth, 75% vs. 63%; excessive salivation, 44% vs. 31%; abnormal bite, 56% vs. 25% Marklund & Franklin P 260 fixed monobloc (105) Frequent users vs. infrequent users; 56% vs. 35% occlusal changes; 32% vs. 19% bad taste; 34% vs. 25% increased salivation; 30% vs. 25% dry mouth; 22% vs. 28% dry lips; 11% vs. 21% TMJ sounds Martinez-Gomis P 40 adjustable duobloc 60 (25) Reduced overjet, overbite, and No. of occlusal contact points Zhou & Llu P 16 adjustable monobloc 1 adjustable duobloc* (0) Ulcers: 12.5%; TMJ: 25%; muscular discomfort: 18.75%; tooth discomfort: 25% Doff P 29 adjustable (0) Overbite: mm; overjet: mm; anteroposterior movement: mm; decrease in No. of posterior occlusal contact points M M joint. *SILENT NITE. Thornton Adjustable Positioner. BMI 5 body mass index; 5 high; M 5 medium; MAD 5 mandibular advancement device; P 5 prospective study; Q 5 quality; TMJ 5 temporomandibular The search strategy included a combination of eight MeS terms: obstructive sleep apnea, sleep apnea syndrome, sleep hypopnea, sleep disordered breathing, mandibular advancement splints, mandibular advancement appliance, oral appliances, and mandibular advancement device. Two reviewers independently assessed the titles and abstracts of all the articles. In the event of disagreement they reached a consensus, but if they continued to disagree they consulted a third reviewer. If the abstract did not provide sufficient information for a definite decision on inclusion or exclusion, the full article was obtained and reviewed before taking the final decision. Data Extraction The following variables were recorded: author, year of publication, sample size, demographic variables (gender and age), follow-up time, losses to follow-up, body mass index, type of MAD used, and indices employed to measure OSAS. The success criteria considered were a 50% reduction in AI or a change in AI level from severe or moderate to mild. 26 The articles were classified as being of high, medium, or low quality according to the CONSORT criteria 25 as adapted by Mattos et al. 27 RESULTS The search identified 241 articles in Medline, three in Cochrane Library Plus, and 149 in Scopus, making a total of 393 articles. Of these, 210 were duplicate references and were excluded. A critical reading of the titles and abstracts eliminated 132 articles, leaving 51 articles of possible interest. After reading the full text of these articles, 26 were excluded because they did not meet the inclusion criteria. Of the remaining 25, three were excluded because they were considered of low quality (Fig. 1). Of the 22 articles selected, 21 reported on prospective studies and one on a retrospective study. Their quality was high in 16 cases and medium in six. The effectiveness of MADs in reducing sleep AI was studied in 18 articles, which showed significant percentages of reduction ranging from 21% to 80%. Of the 18 articles, 16 reported a 50% reduction in AI or a change in AI level from severe or moderate to mild (Table I). Regarding the differences between the various types of MAD, the studies that compared adjustable with fixed or with prefabricated devices showed that in both cases the former were more effective. Oxygen saturation was assessed in 12 articles, most of which reported improvements (Table I). The effectiveness of MADs in decreasing snoring and daytime sleepiness, measured by the ESS, was measured by 11 studies. Almost all of these found significant reductions. The size of the velopharynx was measured in five studies, all of which showed an increase in the dimensions of the upper airway (Table II). Table III shows the adverse effects caused by the use of MADs to treat sleep apnea. The main adverse 511

6 effects described are muscle and joint disorders, changes in salivation, and occlusal changes. DISCUSSION The evidence collected on using MADs to treat OSAS was not abundant, as the rigorous selection of methodologically acceptable articles of medium or high quality limited the number of articles included in this systematic review. On comparing the effectiveness of fixed and adjustable MADs (Tables I and II), Lawton et al. 3 observed that the Twin Block (a fixed MAD) and the erbst (an adjustable MAD) were equally effective in improving AI, snoring, and oxygen saturation but that the erbst appliance gave better results for daytime sleepiness. These results coincide with those of Itzhaki et al., 28 who also found improvements in daytime sleepiness with the erbst appliance. Lettieri et al. 23 obtained satisfactory results with both adjustable and fixed MADs, but the adjustable type gave a greater reduction in AI and improvements in ESS in a greater number of OSAS patients. Tsuiki et al. 2 used adjustable MADs and observed a lowering of the AI in all the patients and an improvement in minimum oxygen saturation. Similar results were obtained by Giannasi et al., 29,30 who also noted that adjustable MADs gave a greater reduction in daytime sleepiness and in snoring than the rigid appliances. Duarte et al. 31 also observed the effectiveness of treating patients with adjustable MADs. In this case the device was inserted at a maximum protrusion of 60%, applying 0.5- to 1-mm increments every 2 weeks. Banhiran et al. 32 found a significant reduction in AI in 60.9% patients with AI < 5 (of whom 75% presented moderate OSAS). These authors used adjustable MADs and applied 0.5- to 1-mm increments every 1 or 2 weeks for 4 to 6 months. In addition to all the above effects, Naismith et al. 33 stated that MADs improve the individual s reaction time and psychomotor component, as well as the subjective perception of sleepiness and fatigue levels. In comparisons of and prefabricated MADs (Tables I and II), Vanderveken et al. 34 compared thermoplastic and appliances in a controlled study. It must not be forgotten that the patient s discomfort and noncompliance with the treatment influence the effectiveness of prefabricated MADs more than that of appliances. Also, the mandibular advancement is greater and better controlled with a MAD. Dieltjens et al. 35 obtained the same results and, additionally, an improvement in snoring and daytime sleepiness. Poon et al. 36 found a significant improvement in AI and oxygen saturation with prefabricated MADs, and also an increase in airway space at the nasopharyngeal level, although not in the velopharynx, contrary to the findings of Tsuiki et al. 2 and Chan et al. 37 Ghazal et al. 38 studied two MADs. Both improved daytime sleepiness and sleep quality after 6 and 24 months, but the Thornton Adjustable Positioner appliance achieved a higher success rate than the IST device. Zhou et al. 39 compared a duobloc and a monobloc MAD. Both improved sleepiness and snoring levels, but 512 a significantly higher decrease in AI was observed with the monobloc appliance. This agrees with the studies of Tsuiki et al., 2 Chan et al., 37 and Poon et al. 36 Both devices increased the upper airway dimensions. As regards the effectiveness of MADs in relation to the airways and orofacial muscles, a number of authors have observed that MADs increase airway size. 2,37,40,41 owever, the methods they employed vary considerably. Brown et al. 40 found that in the patients whose AI decreased, a widening of the upper airway accompanied by posteroanterior movement of the tongue took place during mandibular advancement. Tsuiki et al. 2 obtained similar results. Using nasopharyngoscopy, Chan et al. 37 observed an increase in the dimensions of the velopharynx. This increase was greater in patients whose AI fell by >50%. These authors considered that nasopharyngoscopy could be useful for predicting the outcome of treating OSAS with an MAD and improving the selection of patients for this type of treatment. Kurtulmus et al. 41 observed a significant increase in the electromyographic amplitude of the masseter and submental muscles and concluded that activation of these muscles during sleep prevents airway closure. Most of the articles reviewed agree on the short- and long-term adverse effects caused by MADs. Marklund and Franklin 42 observed increased salivation, dry mouth, bad taste, and occlusal changes, which were greater in the patients who had been using a MAD for longer. Zhou and Llu 39 also recorded ulcers, joint pain, muscular pain, and tooth discomfort. Lawton et al. 3 observed a decrease in adverse effects after 4 to 6 weeks of use. Twin Block users reported less muscle and joint discomfort than those using the erbst device. Similarly, Giannasi et al. 30 stated that the adverse effects did not persist for more than 3 months. Martinez-Gomis et al. 43 did not find any temporomandibular disorders in a 6-year longitudinal study, but did find a significant decrease in overjet, overbite, and the number of posterior occlusal contact points, coinciding with the findings of Doff et al. 44 In relation to the advancement achieved, Aarab et al. 10 observed that the side effects rose considerably from 50% protrusion onward, but the lowest AI results were obtained with 75% protrusion. As regards the material from which the device is made, some authors have found that acrylic MADs present frequent problems such as breakage of the acrylic or the wires. 44,45 Ash and Smith 45 observed that chromecobalt devices afforded greater retention, stability, and patient acceptance and were also kinder to the soft tissues. MADs do not eliminate sleep apnea completely but they do reduce the AI to levels that may be considered mild and they do increase oxygen saturation. Regarding the criteria for successful treatment with MADs, definitions of treatment success in reports of MADs efficacy also vary. For the present review, the studies in which the AI fell by 50% or fell from moderate to mild were considered successful. 26 Of the 18 articles that studied the effectiveness of MADs in reducing the sleep AI, 16 met this criterion of success. Moreover, the MADs presented few side effects, good acceptability compared to CPAP, and an

7 excellent cost/benefit ratio. Consequently, MADs may be considered a treatment of choice for mild/moderate OSAS. One of the main limitations of a systematic review is selection bias. To avoid missing relevant articles, 3 databases were used (Medline, Cochrane Library Plus, and Scopus), although the strict criteria (CONSORT) adopted to select articles of high methodological quality may occasionally have eliminated an article of interest. In an attempt to avoid as much selection bias as possible, no article was excluded on language grounds. CONCLUSION MADs increase the area of the airway. They bring the soft palate, tongue, and hyoid bone forward and activate the masseter and submental muscles, preventing closure. All these effects reduce the AI, increase the oxygen saturation, and improve the main symptoms of OSAS. MADs could be the treatment of choice in patients with mild/moderate OSAS and in severe cases when the patient does not tolerate CPAP. Adjustable and MADs give better results than fixed and prefabricated appliances. Monobloc appliances cause more adverse effects. Adverse effects are generally mild and transient. They usually increase with mandibular protrusion of 50%. The most frequent are changes in salivation, in taste, and in tooth position, such as reduced overjet and overbite, labioversion of lower incisors, upper incisor linguoversion, and lower molar mesialization, as well as muscular and temporomandibular joint discomfort. BIBLIOGRAPY 1. American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; Tsuiki S, Lowe AA, Almeida FR, Kawahata N, Fleetham JA. Effects of mandibular advancement on airway curvature and obstructive sleep apnoea severity. Eur Respir J 2004;23: Lawton M, Battagel JM, Kotecha B. 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