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Oral Appliances in the Management of Obstructive Sleep Apnea

      Keywords

      Key points

      • The concept in oral appliances for obstructive sleep apnea (OSA) management is protrusion of the mandible and/or tongue for structural effects on the upper airway.
      • The upper airway is a muscular tube and its dimensions are enlarged with mandibular and tongue advancement.
      • Protrusion of the mandible and tongue stretches the muscles, thereby reducing upper airway collapsibility with airway shape change and increase in muscle tone.
      • Oral appliances are effective and evidence-based options in managing OSA.

      Types of oral appliances

      The primary oral appliance (OA) used in obstructive sleep apnea (OSA) treatment is the mandibular advancement device (MAD). MADs may be either an over-the-counter stock device or customized for individual patients. MADs come in various designs and materials, but most comprise upper and lower splints mounted over the dentition as either a 1-piece monoblock (Fig. 1) or a 2-piece biblock (Fig. 2). Connectors or blocks relate the upper and lower splints in a biblock to protrude the mandible in a forward position during sleep.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      Figure thumbnail gr1
      Fig. 1Monoblock of 1-piece MAD.
      (Courtesy of the Orthodontic Laboratory in the National Dental Centre of Singapore, Singapore.)
      Figure thumbnail gr2
      Fig. 2Biblock or 2-piece MADs with different connectors.
      (Courtesy of [upper left] SomnoMed, Sydney, Australia; and [upper right, lower left, and lower right] Orthodontic Master, Singapore.)
      Tongue-retaining devices, or tongue-stabilizing devices (TSDs) (Fig. 3), are a second type of OA, which displace the tongue anteriorly and may be customized or come in different stock sizes. TSDs use negative pressure and salivary adhesion to hold onto the tongue and anterior lip shields to elongate and reposition the tongue in a more forward position independent of the mandible during sleep, thereby opening the oropharyngeal airway.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      Figure thumbnail gr3
      Fig. 3TSD.
      (Courtesy of Innovative Health Technologies Ltd, Dunedin, New Zealand.)
      TSDs have similar efficacy as MADs but poorer compliance. More than 90% of patients preferred MADs over TSDs for OA therapy.
      • Deane S.A.
      • Cistulli P.A.
      • Ng A.T.
      • et al.
      Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial.
      The evidence base is stronger for MADs and considerably lower for TSDs.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Chang E.T.
      • Fernandez-Salvador C.
      • Giambo J.
      • et al.
      Tongue retaining devices for obstructive sleep apnea: a systematic review and meta-analysis.

      Oral appliance effects on airway

      Cross-Sectional Area

      Airway imaging with cone-beam computed tomography, magnetic resonance imaging and nasal endoscopy showed anteroposterior (AP) mandibular protrusion predominantly increases the caliber of the airway at the retropalatal area via lateral expansion and displacement of parapharyngeal fat pads
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      • Ishida M.
      • Inoue Y.
      • Suto Y.
      • et al.
      Mechanism of action and therapeutic indication of prosthetic mandibular advancement in obstructive sleep apnea syndrome.
      • Ryan C.F.
      • Love L.L.
      • Peat D.
      • et al.
      Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx.
      • Chan A.S.
      • Lee R.W.
      • Srinivasan V.K.
      • et al.
      Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea.
      • Chan A.S.
      • Sutherland K.
      • Schwab R.J.
      • et al.
      The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea.
      • Kato J.
      • Isono S.
      • Tanaka A.
      • et al.
      Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing.
      • Kuna S.T.
      • Woodson L.C.
      • Solanki D.R.
      • et al.
      Effect of progressive mandibular advancement on pharyngeal airway size in anesthetized adults.
      • Choi J.K.
      • Hur Y.K.
      • Lee J.M.
      • et al.
      Effects of mandibular advancement on upper airway dimension and collapsibility in patients with obstructive sleep apnea using dynamic upper airway imaging during sleep.
      • Brown E.C.
      • Cheng S.
      • McKenzie D.K.
      • et al.
      Tongue and lateral upper airway movement with mandibular advancement.
      while the tongue and tongue-base muscles shift forward.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      • Chan A.S.
      • Sutherland K.
      • Schwab R.J.
      • et al.
      The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea.
      • Brown E.C.
      • Cheng S.
      • McKenzie D.K.
      • et al.
      Tongue and lateral upper airway movement with mandibular advancement.
      The lateral widening from AP movement is attributed to stretching of soft tissue connections between the tongue, soft palate, and lateral pharyngeal walls.
      • Kuna S.T.
      • Woodson L.C.
      • Solanki D.R.
      • et al.
      Effect of progressive mandibular advancement on pharyngeal airway size in anesthetized adults.
      • Isono S.
      • Tanaka A.
      • Sho Y.
      • et al.
      Advancement of the mandible improves velopharyngeal airway patency.
      • Isono S.
      • Tanaka A.
      • Tagaito Y.
      • et al.
      Pharyngeal patency in response to advancement of the mandible in obese anesthetized persons.
      Dynamic MRI suggests a direct connection between lateral pharyngeal walls and the ramus, postulated to be the pterygomandibular raphe.
      • Brown E.C.
      • Cheng S.
      • McKenzie D.K.
      • et al.
      Tongue and lateral upper airway movement with mandibular advancement.
      TSDs increase airway AP diameter to a greater degree than MADs, and traction on intrapharyngeal connections through the tongue base additionally increases the lateral dimension of the airway. Compared with MADs, TSDs produce greater increases in retropalatal and retroglossal cross-sectional area (CSA). This is attributed to greater anterior tongue movement with TSDs.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.

      Other Effects

      Lateral expansion with both MADs and TSDs promotes an elliptical cross-sectional shape with a transverse long axis.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      A small but significant decrease in upper airway length has been found with MAD use,
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      which may counteract the airway length increase from lying supine demonstrated in OSA patients.
      • Pae E.K.
      • Lowe A.A.
      • Fleetham J.A.
      A role of pharyngeal length in obstructive sleep apnea patients.
      Electromyography shows that MADs increase activation of masseter, lateral pterygoid, genioglossus, and geniohyoid muscles. It is postulated that on top of the purely structural anatomic effects of MADs, increased neuromuscular activation contributes to upper airway patency.
      • Yoshida K.
      Effect of a prosthetic appliance for treatment of sleep apnea syndrome on masticatory and tongue muscle activity.
      • Johal A.
      • Gill G.
      • Ferman A.
      • et al.
      The effect of mandibular advancement appliances on awake upper airway and masticatory muscle activity in patients with obstructive sleep apnoea.
      • Kurtulmus H.
      • Cotert S.
      • Bilgen C.
      • et al.
      The effect of a mandibular advancement splint on electromyographic activity of the submental and masseter muscles in patients with obstructive sleep apnea.

      Collapsibility

      Morphologic increase in CSA, change in cross-sectional shape, decrease in airway length, and neuromuscular activation with MAD may contribute to reduced collapsibility.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      • Choi J.K.
      • Hur Y.K.
      • Lee J.M.
      • et al.
      Effects of mandibular advancement on upper airway dimension and collapsibility in patients with obstructive sleep apnea using dynamic upper airway imaging during sleep.
      • Malhotra A.
      • Huang Y.
      • Fogel R.B.
      • et al.
      The male predisposition to pharyngeal collapse: importance of airway length.
      Empirically, a significant reduction in upper airway collapsibility in stage 2 and stage 3 sleep was observed with MAD use. Improvement in collapsibility was significantly greater in complete responders than in partial responders or nonresponders.
      • Ng A.T.
      • Gotsopoulos H.
      • Qian J.
      • et al.
      Effect of oral appliance therapy on upper airway collapsibility in obstructive sleep apnea.
      Airway collapsibility may have a dose-dependent relationship with mandibular advancement.
      • Kato J.
      • Isono S.
      • Tanaka A.
      • et al.
      Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing.

      Oral appliance effects on obstructive sleep apnea compared with continuous positive airway pressure

      Continuous positive airway pressure (CPAP) and MADs are chronic, noninvasive, symptomatic treatments for OSA that do not treat the underlying anatomic basis of the condition. Pneumatic splinting of the airway with CPAP is acknowledged as the gold standard for treatment of OSA, although MAD has been progressively recommended with each iteration of the American Academy of Sleep Medicine (AASM) guidelines.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Kushida C.A.
      • Morgenthaler T.I.
      • Littner M.R.
      • et al.
      Practice parameters for the treatment of snoring and Obstructive Sleep Apnea with oral appliances: an update for 2005.
      Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances. American Sleep Disorders Association.
      The latest AASM guidelines do not specify a particular disease severity for MAD use due to lack of evidence relating MAD efficacy to disease severity.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.

      Apnea-Hypopnea Index

      MADs are efficacious in reducing apnea-hypopnea index (AHI) although there is individual variability.
      • Sutherland K.
      • Vanderveken O.M.
      • Tsuda H.
      • et al.
      Oral appliance treatment for obstructive sleep apnea: an update.
      A nonlinear dose-dependent relationship with degree of advancement is reported.
      • Raphaelson M.A.
      • Alpher E.J.
      • Bakker K.W.
      • et al.
      Oral appliance therapy for obstructive sleep apnea syndrome: progressive mandibular advancement during polysomnography.
      • Tsai W.H.
      • Vazquez J.C.
      • Oshima T.
      • et al.
      Remotely controlled mandibular positioner predicts efficacy of oral appliances in sleep apnea.
      • Gindre L.
      • Gagnadoux F.
      • Meslier N.
      • et al.
      Mandibular advancement for obstructive sleep apnea: dose effect on apnea, long-term use and tolerance.
      • Almeida F.R.
      • Parker J.A.
      • Hodges J.S.
      • et al.
      Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.
      • Aarab G.
      • Lobbezoo F.
      • Hamburger H.L.
      • et al.
      Effects of an oral appliance with different mandibular protrusion positions at a constant vertical dimension on obstructive sleep apnea.
      • Dort L.
      • Remmers J.
      A combination appliance for obstructive sleep apnea: the effectiveness of mandibular advancement and tongue retention.
      The efficacy of CPAP over MAD in reducing AHI is well established and has been consistently reported by meta-analyses comparing the 2,
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Giles T.L.
      • Lasserson T.J.
      • Smith B.H.
      • et al.
      Continuous positive airways pressure for obstructive sleep apnoea in adults.
      • Lim J.
      • Lasserson T.J.
      • Fleetham J.
      • et al.
      Oral appliances for obstructive sleep apnoea.
      • Schwartz M.
      • Acosta L.
      • Hung Y.L.
      • et al.
      Effects of CPAP and mandibular advancement device treatment in obstructive sleep apnea patients: a systematic review and meta-analysis.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.
      even with increasing numbers of primary studies. According to the AASM/American Academy of Dental Sleep Medicine (AADSM) task force, CPAP is significantly better than MAD at reducing AHI scores (difference of 6.24 events per hour).
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      A recent meta-analysis of 14 randomized controlled trials reported that CPAP reduced AHI by an additional 8.43 events per hour over MAD.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.

      Oxygenation

      MADs are efficacious in improving minimum arterial oxygen saturation (Sao2), and the improvement has been reported to have a nonlinear dose-dependent relationship with degree of advancement.
      • Kato J.
      • Isono S.
      • Tanaka A.
      • et al.
      Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing.
      Similar to AHI, the finding of better improvement in Sao2 with CPAP over MAD has been consistently reported.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Giles T.L.
      • Lasserson T.J.
      • Smith B.H.
      • et al.
      Continuous positive airways pressure for obstructive sleep apnoea in adults.
      • Lim J.
      • Lasserson T.J.
      • Fleetham J.
      • et al.
      Oral appliances for obstructive sleep apnoea.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.
      The AASM/AADSM task force reported that CPAP is slightly better at improving oxygenation (Sao2 difference of 3.11%) compared with MADs.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      More recently, a significant effect on Sao2 in favor of CPAP was reported.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.

      Compliance

      Comparing subjective self-reported MAD compliance with objective recorded CPAP compliance, MAD compliance is better. The AASM/AADSM task force reported that MADs were used 0.70 more hours per night than CPAP.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      Objective measurements of OA usage after 3 months of OA treatment ranged from a mean of 6.4 hours to 6.6 hours per night.
      • Dieltjens M.
      • Verbruggen A.E.
      • Braem M.J.
      • et al.
      Determinants of objective compliance during oral appliance therapy in patients with sleep-disordered breathing: a prospective clinical trial.
      • Vanderveken O.M.
      • Dieltjens M.
      • Wouters K.
      • et al.
      Objective measurement of compliance during oral appliance therapy for sleep-disordered breathing.
      A meta-analysis of 6 studies encompassing both subjective and objective MAD compliance measures reported an additional 1.1 hours per night use of MAD over CPAP.
      • Schwartz M.
      • Acosta L.
      • Hung Y.L.
      • et al.
      Effects of CPAP and mandibular advancement device treatment in obstructive sleep apnea patients: a systematic review and meta-analysis.
      A majority of crossover trials report that MADs are preferred to CPAP, which may imply better patient compliance with MADs.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Sutherland K.
      • Phillips C.L.
      • Cistulli P.A.
      Efficacy versus effectiveness in the treatment of obstructive sleep apnea: CPAP and oral appliances.
      • Lettieri C.J.
      • Almeida F.R.
      • Cistulli P.A.
      • et al.
      Oral appliances for the treatment of obstructive sleep apnea-hypopnea syndrome and for concomitant sleep bruxism.
      Depending on OSA severity and total sleep time, less than ideal compliance with CPAP can substantially decrease its effectiveness. Better MAD compliance over CPAP could be why health outcomes of the 2 treatment modalities are similar despite better CPAP efficacy at reducing AHI and increasing oxygenation.
      • Sutherland K.
      • Phillips C.L.
      • Cistulli P.A.
      Efficacy versus effectiveness in the treatment of obstructive sleep apnea: CPAP and oral appliances.

      Subjective Sleepiness

      MADs improve subjective daytime sleepiness measured by Epworth Sleepiness Scale (ESS) scores significantly.
      • Ahrens A.
      • McGrath C.
      • Hagg U.
      Subjective efficacy of oral appliance design features in the management of obstructive sleep apnea: a systematic review.
      Despite better efficacy with CPAP than MADs in reducing AHI and improving Sao2, differences in ESS scores are more ambiguous. A network meta-analysis of 67 studies found that CPAP and MADs are both effective in reducing excessive daytime sleepiness as assessed by the ESS, but CPAP is likely to be more effective than MADs, with a greater reduction in ESS by an average of 0.8 points.
      • Bratton D.J.
      • Gaisl T.
      • Schlatzer C.
      • et al.
      Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
      Other reviews have reported either similar outcomes
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Lim J.
      • Lasserson T.J.
      • Fleetham J.
      • et al.
      Oral appliances for obstructive sleep apnoea.
      or slightly better outcomes with CPAP.
      • Schwartz M.
      • Acosta L.
      • Hung Y.L.
      • et al.
      Effects of CPAP and mandibular advancement device treatment in obstructive sleep apnea patients: a systematic review and meta-analysis.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.

      Function and Quality of Life

      Aside from long-term health effects, untreated OSA also affects health-related quality of life, with hypersomnolence impacting ability to function.
      • Ng A.
      • Gotsopoulos H.
      • Darendeliler A.M.
      • et al.
      Oral appliance therapy for obstructive sleep apnea.
      Function and quality of life are commonly measured using both the sleep-specific Functional Outcomes of Sleep Questionnaire (FOSQ) and generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). MADs are associated with improvements in FOSQ subscale and total scores as well as SF-36 scores.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Blanco J.
      • Zamarron C.
      • Abeleira Pazos M.T.
      • et al.
      Prospective evaluation of an oral appliance in the treatment of obstructive sleep apnea syndrome.
      • Gauthier L.
      • Laberge L.
      • Beaudry M.
      • et al.
      Efficacy of two mandibular advancement appliances in the management of snoring and mild-moderate sleep apnea: a cross-over randomized study.
      Minimal difference was found between CPAP and MAD with respect to improvements in daytime functional outcomes measured by SF-36 and FOSQ scores.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      This finding was corroborated in a meta-analysis,
      • Kuhn E.
      • Schwarz E.I.
      • Bratton D.J.
      • et al.
      Effects of CPAP and mandibular advancement devices on health-related quality of life in OSA: a systematic review and meta-analysis.
      with direct comparisons as well as network meta-analysis showing no significant difference in treatment outcomes between CPAP and MAD in the mental and physical components of SF-36. Other meta-analyses have also reported no difference in FOSQ or SF-36 scores.
      • Giles T.L.
      • Lasserson T.J.
      • Smith B.H.
      • et al.
      Continuous positive airways pressure for obstructive sleep apnoea in adults.
      • Lim J.
      • Lasserson T.J.
      • Fleetham J.
      • et al.
      Oral appliances for obstructive sleep apnoea.
      • Schwartz M.
      • Acosta L.
      • Hung Y.L.
      • et al.
      Effects of CPAP and mandibular advancement device treatment in obstructive sleep apnea patients: a systematic review and meta-analysis.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.

      Cardiovascular Effects

      Meta-analyses by multiple groups have found MADs to be the equivalent of CPAP at reducing blood pressure in adults with OSA.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Zhang M.
      • Liu Y.
      • Liu Y.
      • et al.
      Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: an updated meta-analysis.
      • Bratton D.J.
      • Gaisl T.
      • Wons A.M.
      • et al.
      CPAP vs mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis.
      • de Vries G.E.
      • Wijkstra P.J.
      • Houwerzijl E.J.
      • et al.
      Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: a systematic review and meta-analysis.
      • Van Haesendonck G.
      • Dieltjens M.
      • Kastoer C.
      • et al.
      Cardiovascular benefits of oral appliance therapy in obstructive sleep apnea: a systematic review.
      A network meta-analysis reported that CPAP was associated with a reduction in systolic blood pressure of 2.5 mm Hg and diastolic blood pressure reduction of 2.0 mm Hg. MADs were associated with reduction in systolic blood pressure of 2.1 mm Hg and diastolic blood pressure of 1.9 mm Hg. There was no significant difference between CPAP and MADs.
      • Bratton D.J.
      • Gaisl T.
      • Schlatzer C.
      • et al.
      Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
      Studies on other cardiovascular markers (heart rate variability, circulating cardiovascular biomarkers, endothelial function, and arterial stiffness) were deemed heterogeneous and inconclusive.
      • de Vries G.E.
      • Wijkstra P.J.
      • Houwerzijl E.J.
      • et al.
      Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: a systematic review and meta-analysis.

      Mortality

      A prospective cohort study on long-term cardiovascular mortality in 208 subjects found CPAP and MAD equally effective in reducing the risk of fatal cardiovascular events in patients with severe OSA, despite higher residual AHI for MAD compared with CPAP users (16.3 vs 4.5 events per hour). There was no difference in the cumulative cardiovascular mortality between OSA patients treated with CPAP or MAD and that of the nonapneic controls, suggesting effective symptomatic treatment with either modality despite differences in residual AHI.
      • Anandam A.
      • Patil M.
      • Akinnusi M.
      • et al.
      Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study.
      This outcome, however, is from a single observational study. More longitudinal studies with better methodology are needed to answer key questions on cardiovascular morbidity and mortality outcomes.
      • de Vries G.E.
      • Wijkstra P.J.
      • Houwerzijl E.J.
      • et al.
      Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: a systematic review and meta-analysis.
      • Anandam A.
      • Patil M.
      • Akinnusi M.
      • et al.
      Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study.

      Oral appliance adverse effects

      Similar to efficacy, adverse side effects have a dose-dependent relationship with protrusion.
      • Aarab G.
      • Lobbezoo F.
      • Hamburger H.L.
      • et al.
      Effects of an oral appliance with different mandibular protrusion positions at a constant vertical dimension on obstructive sleep apnea.
      A balance must be struck between efficacy and side effects because more adverse effects reduce long-term compliance,
      • Dieltjens M.
      • Verbruggen A.E.
      • Braem M.J.
      • et al.
      Determinants of objective compliance during oral appliance therapy in patients with sleep-disordered breathing: a prospective clinical trial.
      • Attali V.
      • Chaumereuil C.
      • Arnulf I.
      • et al.
      Predictors of long-term effectiveness to mandibular repositioning device treatment in obstructive sleep apnea patients after 1000 days.
      resulting in patients terminating MAD therapy.
      • Marklund M.
      • Stenlund H.
      • Franklin K.A.
      Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      Most adverse effects caused by MADs are mild and transient, occur during the initial phase of therapy, and tend to resolve with time.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      • Ferguson K.A.
      • Cartwright R.
      • Rogers R.
      • et al.
      Oral appliances for snoring and obstructive sleep apnea: a review.

      Dental Effects

      Long-term use of OAs leads to occlusal changes. A meta-analysis reported a significant increase in lower incisor inclination by 2.07°, resulting in 0.99-mm decrease in overjet (OJ) and 1.0-mm decrease in overbite (OB). A greater decrease in OJ and OB was associated with longer treatment. There was no significant change in the upper incisor inclination or interincisal angle.
      • Araie T.
      • Okuno K.
      • Ono Minagi H.
      • et al.
      Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: a systematic review and meta-analysis.
      Due to the lower incisor inclination change and attendant decrease in OJ and OB, there was significant increase in anterior crossbites,
      • Pliska B.T.
      • Nam H.
      • Chen H.
      • et al.
      Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment.
      increase in mandibular arch width, and reduction in lower arch crowding.
      • Pliska B.T.
      • Nam H.
      • Chen H.
      • et al.
      Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment.
      • Chen H.
      • Lowe A.A.
      • de Almeida F.R.
      • et al.
      Three-dimensional computer-assisted study model analysis of long-term oral-appliance wear. Part 2. Side effects of oral appliances in obstructive sleep apnea patients.
      Maxillary arch width increase and upper arch decrowding also have been reported.
      • Chen H.
      • Lowe A.A.
      • de Almeida F.R.
      • et al.
      Three-dimensional computer-assisted study model analysis of long-term oral-appliance wear. Part 2. Side effects of oral appliances in obstructive sleep apnea patients.
      A decrease in posterior occlusal contacts
      • Pliska B.T.
      • Nam H.
      • Chen H.
      • et al.
      Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment.
      • Otsuka R.
      • Almeida F.R.
      • Lowe A.A.
      The effects of oral appliance therapy on occlusal function in patients with obstructive sleep apnea: a short-term prospective study.
      • Martinez-Gomis J.
      • Willaert E.
      • Nogues L.
      • et al.
      Five years of sleep apnea treatment with a mandibular advancement device. Side effects and technical complications.
      • Fransson A.M.C.
      • Kowalczyk A.
      • Isacsson G.
      A prospective 10-year follow-up dental cast study of patients with obstructive sleep apnoea/snoring who use a mandibular protruding device.
      may result in a transient difficulty with chewing.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      Although the magnitude of dental changes are small, they may be significant to patient perception of developing dental malocclusion.
      • Alessandri-Bonetti G.
      • D'Anto V.
      • Stipa C.
      • et al.
      Dentoskeletal effects of oral appliance wear in obstructive sleep apnoea and snoring patients.

      Craniofacial Changes

      A meta-analysis of skeletal changes from MAD use reported no significant skeletal changes.
      • Araie T.
      • Okuno K.
      • Ono Minagi H.
      • et al.
      Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: a systematic review and meta-analysis.
      Other investigators, however, report significant increase in lower and total anterior facial height from long-term MAD use of more than 2 years.
      • Almeida F.R.
      • Lowe A.A.
      • Sung J.O.
      • et al.
      Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: Part 1. Cephalometric analysis.
      • Doff M.H.
      • Hoekema A.
      • Pruim G.J.
      • et al.
      Long-term oral-appliance therapy in obstructive sleep apnea: a cephalometric study of craniofacial changes.

      Temporomandibular Joint Disorders

      Transient muscle soreness and temporomandibular joint (TMJ) discomfort have been reported after MAD use, especially during the initial titration period.
      • Deane S.A.
      • Cistulli P.A.
      • Ng A.T.
      • et al.
      Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      A 5-year follow-up study of MAD patients found mild, temporary subjective side effects, such as muscular or TMJ discomfort, but no changes in temporomandibular disorder prevalence using the Research Diagnostic Criteria for Temporomandibular Disorders.
      • Martinez-Gomis J.
      • Willaert E.
      • Nogues L.
      • et al.
      Five years of sleep apnea treatment with a mandibular advancement device. Side effects and technical complications.

      Other Effects

      Other MAD side effects include increased salivation, more frequent and excessive dry mouth, tongue discomfort, and a sense of suffocation.
      • Deane S.A.
      • Cistulli P.A.
      • Ng A.T.
      • et al.
      Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial.
      • Dieltjens M.
      • Verbruggen A.E.
      • Braem M.J.
      • et al.
      Determinants of objective compliance during oral appliance therapy in patients with sleep-disordered breathing: a prospective clinical trial.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      TSD side effects include excess salivation, drooling, dry mouth, and soft tissue irritation.
      • Deane S.A.
      • Cistulli P.A.
      • Ng A.T.
      • et al.
      Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial.

      Predicting and improving oral appliance treatment response

      Although most patients show an increased airway CSA with mandibular advancement, a minority of patients show no change or even a decreased CSA.
      • Chan A.S.
      • Sutherland K.
      • Schwab R.J.
      • et al.
      The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea.
      • Choi J.K.
      • Hur Y.K.
      • Lee J.M.
      • et al.
      Effects of mandibular advancement on upper airway dimension and collapsibility in patients with obstructive sleep apnea using dynamic upper airway imaging during sleep.
      MAD is a primarily structural treatment
      • Chan A.S.
      • Sutherland K.
      • Schwab R.J.
      • et al.
      The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea.
      for a heterogeneous condition with nonanatomic etiology in up to 56% of patients.
      • Eckert D.J.
      • White D.P.
      • Jordan A.S.
      • et al.
      Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets.
      • Edwards B.A.
      • Eckert D.J.
      • Jordan A.S.
      Obstructive sleep apnoea pathogenesis from mild to severe: is it all the same?.
      Consequently, MAD treatment completely resolves AHI to fewer than 5 events per hour in only 36% to 70% of OSA patients.
      • Sutherland K.
      • Vanderveken O.M.
      • Tsuda H.
      • et al.
      Oral appliance treatment for obstructive sleep apnea: an update.
      • Lettieri C.J.
      • Almeida F.R.
      • Cistulli P.A.
      • et al.
      Oral appliances for the treatment of obstructive sleep apnea-hypopnea syndrome and for concomitant sleep bruxism.
      Patients of female gender, younger age, smaller neck circumference, lower body mass index, lower AHI, and supine-dependent OSA are predicted to have better treatment success with MADs.
      • Lettieri C.J.
      • Almeida F.R.
      • Cistulli P.A.
      • et al.
      Oral appliances for the treatment of obstructive sleep apnea-hypopnea syndrome and for concomitant sleep bruxism.
      • Marklund M.
      • Stenlund H.
      • Franklin K.A.
      Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success.
      • Liu Y.
      • Lowe A.A.
      • Fleetham J.A.
      • et al.
      Cephalometric and physiologic predictors of the efficacy of an adjustable oral appliance for treating obstructive sleep apnea.
      • Okuno K.
      • Pliska B.T.
      • Hamoda M.
      • et al.
      Prediction of oral appliance treatment outcomes in obstructive sleep apnea: a systematic review.
      For TSDs, the best predictor of success is believed to be the presence of a single-site airway obstruction in supine-dependent OSA.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      There is currently no validated clinical method to reliably differentiate responders from nonresponders.
      • Sutherland K.
      • Vanderveken O.M.
      • Tsuda H.
      • et al.
      Oral appliance treatment for obstructive sleep apnea: an update.
      Uncertainty of MAD treatment response is exacerbated by cost of treatment.

      American Sleep Assocociation | sleep apnea oral appliances - research & treatments | 2018. Available at: https://www.sleepassociation.org/sleep-disorders/sleep-apnea/oral-appliance-for-sleep-apnea/. Accessed July 22, 2018.

      The literature lacks consensus in successful treatment outcome, with a majority of success criteria used in research not meshing with clinical definitions of OSA severity. Discordant success criteria makes comparing results of different studies difficult.
      • Dieltjens M.
      • Vanderveken O.M.
      • Heyning P.H.
      • et al.
      Current opinions and clinical practice in the titration of oral appliances in the treatment of sleep-disordered breathing.
      Prospective trials are under way to determine predictive potential of wakeful nasoendoscopy with Müller maneuver, drug-induced sleep endoscopy (DISE), and computational fluid dynamics.
      • Verbruggen A.E.
      • Vroegop A.V.
      • Dieltjens M.
      • et al.
      Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnoea (PROMAD): study design and baseline characteristics.

      National Institutes of Health, United States National Library of Medicine, ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/record/NCT01532050. Accessed 26 July, 2018.

      In the meantime, careful diagnosis and patient selection can increase the chances of success.

      Cephalometry

      Classically, shorter soft palate length, larger retropalatal airway space, lower hyoid bone position, and a smaller mandible are associated with favorable MAD treatment response.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      • Okuno K.
      • Pliska B.T.
      • Hamoda M.
      • et al.
      Prediction of oral appliance treatment outcomes in obstructive sleep apnea: a systematic review.
      Two recent systematic reviews,
      • Alessandri-Bonetti G.
      • Ippolito D.R.
      • Bartolucci M.L.
      • et al.
      Cephalometric predictors of treatment outcome with mandibular advancement devices in adult patients with obstructive sleep apnea: a systematic review.
      • Guarda-Nardini L.
      • Manfredini D.
      • Mion M.
      • et al.
      Anatomically based outcome predictors of treatment for obstructive sleep apnea with intraoral splint devices: a systematic review of cephalometric studies.
      however, exploring cephalometric predictors for MAD response found a majority of observational studies on cephalometric predictors had flawed designs and failed to control for known confounding factors such as age, gender, body mass index, and baseline AHI. Definitions of treatment success were inconsistent, and heterogeneity in design prevented data synthesis and meta-analysis. Cephalometric parameters warranting further study included mandibular plane angle, hyoid to mandibular plane distance, and soft palate length.

      Mandibular Advancement Device Design

      Customized versus noncustomized

      Both customized and noncustomized MADs reduce AHI in adult patients with OSA, but meta-analysis by the AASM/AADSM task force shows the improvements to be far greater in customized than noncustomized, with an AHI reduction of 13.89 events compared with 6.28 events per hour.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      Noncustomized MADs do not improve minimum Sao2, whereas customized MADs increase Sao2 by 3.22%.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      They also do not reduce ESS scores to any significant level,
      • Vanderveken O.M.
      • Devolder A.
      • Marklund M.
      • et al.
      Comparison of a custom-made and a thermoplastic oral appliance for the treatment of mild sleep apnea.
      whereas modest improvements in ESS scores can be expected from customized MADs.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.

      Titratable versus nontitratable

      Both custom titratable and custom nontitratable MADs reduce AHI, improve Sao2 and reduce ESS scores, with meta-analyses by the AASM/AADSM task force showing the improvements to be approximately equivalent. Titratable MADs are recommended, however, over nontitratable MADs because the confidence interval for the effect of custom, titratable MADs is considerably smaller than for custom, nontitratable MADs.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      Due to dose-dependent effects, a clinical titration can improve MAD response and increase the amount of achievable protrusion. This is only possible with titratable MADs.
      • Gindre L.
      • Gagnadoux F.
      • Meslier N.
      • et al.
      Mandibular advancement for obstructive sleep apnea: dose effect on apnea, long-term use and tolerance.

      Therapeutic Diagnosis

      Visualizing airway response

      Treatment response to MAD can be estimated by visualizing airway response to mandibular protrusion or tongue thrust with nasoendoscopy or MRI in awake supine patients, or in patients using DISE. An increase in velopharyngeal CSA with mandibular advancement was significantly associated with greater AHI reduction with MADs.
      • Chan A.S.
      • Lee R.W.
      • Srinivasan V.K.
      • et al.
      Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea.
      • Chan A.S.
      • Sutherland K.
      • Schwab R.J.
      • et al.
      The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea.
      • Sasao Y.
      • Nohara K.
      • Okuno K.
      • et al.
      Videoendoscopic diagnosis for predicting the response to oral appliance therapy in severe obstructive sleep apnea.
      • Vroegop A.V.
      • Vanderveken O.M.
      • Dieltjens M.
      • et al.
      Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome.
      This was not fully predictive, however, with some patients without velopharyngeal widening showing high AHI reductions and vice versa.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      • Sasao Y.
      • Nohara K.
      • Okuno K.
      • et al.
      Videoendoscopic diagnosis for predicting the response to oral appliance therapy in severe obstructive sleep apnea.
      Müller maneuver during nasoendoscopy induced significantly greater collapse in velopharyngeal and oropharyngeal CSA in MAD nonresponders than responders. With mandibular advancement, Müller maneuver induced a significantly greater collapse at all airway levels in nonresponders.
      • Chan A.S.
      • Lee R.W.
      • Srinivasan V.K.
      • et al.
      Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea.
      On MRI, TSD responders showed a greater increase with TSD in AP diameter, minimum and mean CSA, and volume compared with nonresponders.
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.

      Mandibular advancement device titration using polysomnography

      Due to the dose-dependent relationship between efficacy and protrusion, increasing protrusion can increase treatment response in OSA patients. Conventional titration protocols use subjective symptoms to adjust mandibular advancement over several months and an outcome polysomnography (PSG) to confirm efficacy. There is no consensus, however, on an optimal titration protocol.
      • Dieltjens M.
      • Vanderveken O.M.
      • Heyning P.H.
      • et al.
      Current opinions and clinical practice in the titration of oral appliances in the treatment of sleep-disordered breathing.
      Manually increasing MAD advancement during overnight PSG can increase therapeutic efficacy of mandibular protrusion while reducing the number of titration visits required by most therapeutic protocols. After a clinical titration period, overnight MAD titration with PSG using the final MAD increased treatment response by an additional 9.9% to 30.4% of study subjects.
      • Almeida F.R.
      • Parker J.A.
      • Hodges J.S.
      • et al.
      Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.
      • Krishnan V.
      • Collop N.A.
      • Scherr S.C.
      An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea.
      Disappointing outcomes were reported, however, using an interim MAD without a period of clinical titration because efficacy of the interim MAD was not translated to the final MAD.
      • Kuna S.T.
      • Giarraputo P.C.
      • Stanton D.C.
      • et al.
      Evaluation of an oral mandibular advancement titration appliance.
      Overnight MAD titration with PSG may require large single-night mandibular advancements to relieve respiratory events, in contrast to slow titration with conventional protocols. Significant jaw discomfort was noted with PSG titration without prior MAD use
      • Kuna S.T.
      • Giarraputo P.C.
      • Stanton D.C.
      • et al.
      Evaluation of an oral mandibular advancement titration appliance.
      but was not reported by patients who had an adaptation period with conventional clinical MAD titration.
      • Almeida F.R.
      • Parker J.A.
      • Hodges J.S.
      • et al.
      Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.

      Remote-controlled mandibular positioners

      Using remote-controlled mandibular positioners (RCMPs) for single-night titration of MADs is similar to overnight MAD titration with PSG, with the advantage of adjustment done remotely without waking the patient or removing the appliance. Sleep architecture is maintained while protruding the mandible progressively until respiratory events are eliminated.
      • Tsai W.H.
      • Vazquez J.C.
      • Oshima T.
      • et al.
      Remotely controlled mandibular positioner predicts efficacy of oral appliances in sleep apnea.
      • Petelle B.
      • Vincent G.
      • Gagnadoux F.
      • et al.
      One-night mandibular advancement titration for obstructive sleep apnea syndrome: a pilot study.
      • Dort L.C.
      • Hadjuk E.
      • Remmers J.E.
      Mandibular advancement and obstructive sleep apnoea: a method for determining effective mandibular protrusion.
      • Remmers J.
      • Charkhandeh S.
      • Grosse J.
      • et al.
      Remotely controlled mandibular protrusion during sleep predicts therapeutic success with oral appliances in patients with obstructive sleep apnea.
      • Sutherland K.
      • Ngiam J.
      • Cistulli P.A.
      Performance of remotely controlled mandibular protrusion sleep studies for prediction of oral appliance treatment response.
      RCMPs can determine an effective target protrusion that is correlated with successful MAD treatment, may be able to identify nonresponders early, and reduce the number of titration reviews needed compared with conventional titration protocols.
      • Kastoer C.
      • Dieltjens M.
      • Oorts E.
      • et al.
      The use of remotely controlled mandibular positioner as a predictive screening tool for mandibular advancement device therapy in patients with obstructive sleep apnea through single-night progressive titration of the mandible: a systematic review.
      RCMP titration, however, necessitates large single-night mandibular advancements, which can cause significant jaw discomfort.
      • Tsai W.H.
      • Vazquez J.C.
      • Oshima T.
      • et al.
      Remotely controlled mandibular positioner predicts efficacy of oral appliances in sleep apnea.

      Combination Therapy

      Mandibular advancement device and tongue-stabilizing devices

      Because TSDs have somewhat different anatomic effects on the airway compared with MADs,
      • Sutherland K.
      • Deane S.A.
      • Chan A.S.
      • et al.
      Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
      combining the therapies using a novel hybrid appliance resulted in augmentative treatment effects. Tongue suction with 6 mm mandibular protrusion produced better treatment response than 8 mm mandibular protrusion alone.
      • Dort L.
      • Remmers J.
      A combination appliance for obstructive sleep apnea: the effectiveness of mandibular advancement and tongue retention.
      Combination therapy might improve OA treatment response and prove useful in patients with limited mandibular protrusion.

      Mandibular advancement device and continuous positive airway pressure

      Combining MAD and CPAP lowered the therapeutic CPAP pressure.
      • Denbar M.A.
      A case study involving the combination treatment of an oral appliance and auto-titrating CPAP unit.
      • El-Solh A.A.
      • Moitheennazima B.
      • Akinnusi M.E.
      • et al.
      Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study.
      • Liu H.W.
      • Chen Y.J.
      • Lai Y.C.
      • et al.
      Combining MAD and CPAP as an effective strategy for treating patients with severe sleep apnea intolerant to high-pressure PAP and unresponsive to MAD.
      • de Vries G.E.
      • Doff M.H.J.
      • Hoekema A.
      • et al.
      Continuous positive airway pressure and oral appliance hybrid therapy in obstructive sleep apnea: patient comfort, compliance, and preference: a pilot study.
      An augmentative treatment effect on reducing AHI was found in patients not responding to CPAP or MAD use alone.
      • Denbar M.A.
      A case study involving the combination treatment of an oral appliance and auto-titrating CPAP unit.
      • El-Solh A.A.
      • Moitheennazima B.
      • Akinnusi M.E.
      • et al.
      Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study.
      • Liu H.W.
      • Chen Y.J.
      • Lai Y.C.
      • et al.
      Combining MAD and CPAP as an effective strategy for treating patients with severe sleep apnea intolerant to high-pressure PAP and unresponsive to MAD.

      Practice recommendations

      Indications

      OAs in the form of MADs can be used as an alternative for patients of all OSA severities who are intolerant of CPAP or prefer an alternative therapy.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.

      Contraindications

      Patients who are generally unsuitable for MAD treatment include edentulous patients and patients with inadequate number of sound teeth, severe periodontitis, and/or history of TMJ disease. There are exceptions, and MADs can sometimes be worn successfully by edentulous patients with good dentoalveolar ridges.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      TSDs are not dependent on the dentition for retention and can be prescribed for edentulous or insufficiently dentate patients.

      Appliance Selection

      A plethora of designs is currently in use.
      • Yow M.
      An overview of oral appliances and managing the airway in obstructive sleep apnea.
      Based on current evidence, customized, titratable MADs are the preferred form of OAs.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      TSDs can be used in MAD nonresponders who want OA therapy.

      Clinical Follow-up

      Trained dentists in sleep practice should follow-up patients using MADs to reduce dental side effects and occlusal changes.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      Initial side effects are transient and reversible.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      • Ferguson K.A.
      • Cartwright R.
      • Rogers R.
      • et al.
      Oral appliances for snoring and obstructive sleep apnea: a review.
      Close monitoring and coaching through the initial period may improve compliance.
      • Dieltjens M.
      • Verbruggen A.E.
      • Braem M.J.
      • et al.
      Determinants of objective compliance during oral appliance therapy in patients with sleep-disordered breathing: a prospective clinical trial.
      • Marklund M.
      • Stenlund H.
      • Franklin K.A.
      Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success.
      • de Almeida F.R.
      • Lowe A.A.
      • Tsuiki S.
      • et al.
      Long-term compliance and side effects of oral appliances used for the treatment of snoring and obstructive sleep apnea syndrome.
      For initial comfort, mandibular advancement is 75% of maximum protrusion.
      • Yow M.
      • Lye E.K.W.
      Obstructive sleep apnea: orthodontic startegies to establish and maintain a patent airway.
      Clinical titration with an adaptation period increases the achievable protrusion and improves treatment response.
      • Gindre L.
      • Gagnadoux F.
      • Meslier N.
      • et al.
      Mandibular advancement for obstructive sleep apnea: dose effect on apnea, long-term use and tolerance.
      Clinical titration should be followed by overnight PSG. Subjective feedback is not sufficient to determine the optimal setting of MAD. Post-PSG titration has been shown to improve MAD efficacy significantly.
      • Ramar K.
      • Dort L.C.
      • Katz S.G.
      • et al.
      Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
      • Almeida F.R.
      • Parker J.A.
      • Hodges J.S.
      • et al.
      Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.
      • Krishnan V.
      • Collop N.A.
      • Scherr S.C.
      An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea.

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        • Yow M.
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        Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea.
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        Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial.
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        Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015.
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