Introduction Treatment of sleep-disordered breathing (i.e. snoring, upper airway resistance syndrome, sleep apnea syndrome) can be divided into four general categories. These include: (1) lifestyle modification, i.e. weight loss, cessation of evening alcohol ingestion, sleep position training, (2) upper airway surgery, (3) oral appliances, and (4) CPAP. Although the latter category provides the most reliable therapeutic modality and is the most widely used method to treat sleep-disordered breathing today—it is also the most cumbersome one. Many patients, particularly young non-apneic snorers, find it unappealing, difficult to tolerate, and unacceptable. The only other non-invasive alternative, which can produce favorable results within a short time, is oral appliances. 1 6 124 125 7 This review will summarize our current state of knowledge of the efficacy of oral appliances for the treatment of snoring and obstructive sleep apnea. We shall not limit this review to a simple summary of the effect of oral appliances on nocturnal respiration, but will also examine other aspects of this therapy, such as the reduction in symptoms, vascular consequences, side effects, and compliance. However, the main objective of this review will remain to be the examination of the current data dealing with the efficacy of oral appliance therapy for the treatment of snoring and sleep apnea. Historical aspects 8 1 Fig. 1 Examples of early oral appliances  9 10 11 Types of appliances 1 Table 1 Examples of oral appliances Oral appliances The Equilizer Jasper jumper Esmark The Silencer PM Positioner TPE Klearway Tongue locking appliance SnoreEx NAPA Adjustable soft palate lifter HAP TAP Z-training appliance Tessi TOPS Snore-no-more Snore Guard SNOAR Elastometric Silent Night Herbst SUAD TheraSnore Mechanism of action of oral appliances 12 13 14 19 120 123 19 123 120 20 Results of clinical trials 11 In what follows, we shall summarize the results of clinical trials employing oral appliances for the treatment of sleep apnea and snoring. In addition, we shall review and summarize the information regarding changes in daytime function as a result of using the appliance, clinical and dental side effects, and compliance with treatment. Oral appliances for the treatment of sleep apnea 2 11 Table 2 Clinical studies with oral appliances: 1982–2005 Reference N Type base appl Success rate (%) Response rate (%) Comments 11 14 TRD 56 27 14 14 Case series; AI 22 16 TRD 54 33 19 32 Case series; AI 23 16 TRD – – – 56 Case series; all patients had SMR or UPPP; AI 24 1 TRD 79 5 100 – Case report; AI 25 7 MAA 37 12 57 43 Case series; Esmarch prosthesis; AI 26 44 MAA 50 23 – 59 Case series; Esmarch prosthesis; AI 27 5 TRD 48 9 40 60 Case series; NAPA; AI 28 12 MAA 54 36 25 17 Case series; modified functional appliance 29 1 MAA 35 9 100 – Case report; mandibular repositioning appliance 30 12 TRD 37 17 58 17 Case series 31 1 MAA 57 2 100 – Case report; mandibular repositioning appliance 32 15 TRD 27 11 73 0 Case series 33 14 MAA 32 9 43 57 Case series; fixed splint; AI 34 20 MAA 47 20 35 40 Case series; fixed dental orthosis 35 12 MAA 50 19 – – Case series; fixed prosthesis; AI 36 2 MAA 30 7 50 50 Two case reports; intra-oral fixed prosthesis; RDI 37 16 MAA 37 9 69 25 Case series; NAPA; RDI 38 24 MAA 48 12 73 13 Prospective case series; Herbst-like; RDI 39 19 MAA 35 13 – – Case series of CPAP failures; Herbst 40 20 MAA 57 26 20 40 Case series; Esmarch; AI 41 12 MAA 45 30 – – Case series; Herbst vs MR (muscle relaxation) appliance; result for Herbst; ODI4 41 12 MAA 45 41 – – Case series; Herbst vs MR (muscle relaxation) appliance; result for MR; ODI4 42 51 MAA 32 18 – – Case series; mandibular advancement splint fixed 75% of maximum protrusion 43 4 MAA 200 110 – 75 Case series; fixed intra-oral prosthesis; apneas/night 44 30 MAA 65 31 – – Case series; Esmarch; AI 45 21 MAA 34 20 19 24 Crossover, comparing AMP device with CPAP 46 19 MAA 20 10 68 11 Randomized, prospective crossover comparing the Snore-Guard with CPAP 47 23 MAA 37 18 52 30 Case series; mandibular repositioning device;most patients were CPAP failures; RDI 48 1 MAA 34 3 100 – Case report; elastometric sleep appliance 49 14 TRD 38 30 0 0 Case series: SnorEx appliance; RDI 50 20 MAA 25 14 55 21 Randomized, crossover comparing the AMP device with CPAP 51 8 MAA 44 12 63 13 Case series; mandibular advancing positioner 52 1 MAA 53 4 100 – Case report; fixed dental appliance 53 14 MAA 4 4 – – Fixed mandibular splint; maximum protrusion; median AHI 53 9 MAA 7 1 – – Fixed mandibular splint; 70% of maximum protrusion; median AHI 54 44 MAA 25 9 64 16 Case series, prospective; mandibular advancement device 55 18 MAA 42 15 61 11 Case series of UPPP failures; Herbst 56 25 MAA 33 9 72 12 Case series;mandibular positioning device; RDI 57 15 MAA 193 20 – – Case series of snorers; mandibular advancement device; snores/h of sleep 58 14 MAA 36 5 71 21 Case series; Serenox 59 41 MAA 18 12 78 3 Prospective, randomized, parallel groups comparing dental appliance with UPPP 60 75 MAA 44 12 51 28 Case series; TAP appliance 61 11 MAA 45 10 – – Case series; dental appliance 62 15 MAA 28 8 – – Case series; Klearway appliance 63 28 MAA 53 21 32 36 Case series; elastic mandibular advancement device 64 37 MAA 26 11 50 15 Case series; three fixed appliances with 2, 4 and 6 mm protrusion; ODI4 65 8 MAA 72 36 13 50 Case series comparing MAA (Snore-Guard) with TRD and with soft palate lifter (SPL) 65 5 TRD 50 44 – – Ibid 65 2 SPL 47 57 – – Ibid 66 10 MAA 41 12 60 30 Case series; Herbst 67 38 MAA 33 12 55 18 Case series; Klearway 68 24 MAA 23 9 67 – Randomized, crossover comparing Herbst vs monoblock; results given for Herbst 69 39 MAA 17 8 59 – Case series; SnorBan 70 256 MAA 43 18 54 14 Case series; mandibular advancement device 71 22 MAA 40 12 59 23 Case series; modified functional appliance 72 24 MAA 30 14 38 25 Randomized, placebo-appliance-controlled, crossover; mandibular advancement splint 73 22 MAA 28 6 – – Case series; either Herbst or monoblock 74 72 MAA 43 22 53 22 Case series; adjustable mandibular splints 75 25 MAA 3.4 1.8 – – Randomized, placebo-appliance-controlled, crossover series of snorers; snoring measured on a 0–4 scale 76 33 MAA 25 9 58 – Prospective case series; mandibular advancement device 77 23 MAA 21 8 52 22 Randomized, crossover, comparing 4 mm with 14 mm inter-incisal opening; results for 4 mm opening 78 7 MAA 67 20 43 43 Case series; Herbst-like 79 32 MAA 18 7 63 9 Randomized, parallel groups comparing UPPP and MAA 80 26 MAA 18 8 88 12 Case series; Karwetzky activator 81 34 MAA 22 7 – – Case series; Karwetzky activator; median AHIs 82 73 MAA 27 12 36 27 Randomized, crossover, placebo-appliance-controlled 83 6 MAA 13 6 83 0 Case series; titration study; results for maximum protrusion; Klearway 84 20 MAA 18 14 30 – Randomized, crossover, comparing CPAP with ISAD appliance 85 48 MAA 31 15 47 – Randomized, crossover, comparing CPAP with mandibular repositioning splint 86 20 MAA 38 23 33 – Randomized, crossover, placebo-appliance-controlled; mandibular advancement splint 87 34 MAA 29 4 – – Case series comparing patients on CPAP who switched to MAA 88 24 MAA 22 8 70 – Prospective randomized crossover, comparing MAS with CPAP; soft one-piece mandibular advancement splint 89 40 MAA 50 16 52 28 Prospective, randomized, parallel groups comparing 75% and 50% of mandibular protrusion; results for 75% group 90 26 MAA 19 6 73 4 Prospective, randomized, parallel groups comparing 75% and 50% of mandibular protrusion; results for 75% group 91 25 MAA 38 15 44 24 Case series; The Silencer appliance 92 80 MAA 21 14 – – Randomized, crossover, controlled, comparing mandibular advancement splint with CPAP and with placebo tablet 93 44 MAA 46 12 64 18 Case series; titration protocol; Herbst-like 94 19 MAA 34 17 37 11 Case series; titration protocol; Klearway 95 277 MAA 21 8 54 – Case series; mandibular advancement devices 96 11 MAA 3 2 – – Prospective case series of non-apneic snorers; Herbst; ODI4 97 20 MAA 8 4 – – Case series; fixed mandibular advancement device 98 34 MAA 20 3 94 0 Case series of consecutive patients; TAP appliance 99 17 MAA 25 15 – – Case series of patients with CHF; mandibular advancement device 19 19 MAA 32 8 79 11 Case series; Herbst 100 16 MAA 46 24 – – Prospective, randomized, crossover comparing Twin Block and Herbst; median AHI  101 251 MAA 29 16 – – Mail survey of 544 patients; RDI; mainly Klearway, few mandibular repositioners, fewer TRDs 114 21 MAA 34 25 5 38 Case series; Klearway appliance 115 92 MAA 18 – – – Case series; questionnaires; bed partners’ replies recorded 120 25 MAA 35.9 8.2 60 – Median AHI; case series; 6 weeks use; split polysomnography 121 4 MAA 49.5 11.7 75 25 Case series 122 73 MAA 24.4 12.2 55 – Prospective, randomized, placebo-appliance-controlled 4 weeks study 123 12 MAA 22 9.2 58 – Case series 126 161 MAA 18 6 59 22 Case series; OSA defined as AHI > 5 2 2 2 base appl base base 2 appl appl base Clearly, it is not possible to carry out a meta-analysis of these studies because of the differences in study design, data collection, statistical analysis and presentation of the data. Even the simple descriptive statistics based on the pooled data must be interpreted with caution due to the methodological differences listed above. To obtain the general information about the efficacy of oral appliances, we analyzed the results of individual investigations in several different ways, as follows. 24 29 31 48 52 43 53 57 64 75 81 96 100 120 base appl base 23 appl 23 115 2 3 base Table 3 2 Variable Result No. of patients No. of studies base 31 2,816 74 appl 14 2,724 73 Response rate 21% 1,577 51 Success rate 54% 2,087 59 2 base appl 4 Table 4 Summary of results for complete studies Results for complete studies No. of studies 49 No. of patients 1,517 base 35 appl 14 Response rate 20% Success rate 54% 72 82 86 122 92 5 base Table 5 Summary of results if randomized, crossover, placebo-controlled studies Reference N base appl Success rate (%) Response rate (%) Comments 72 24 30 14 38 25 For AHI = 5 cut-off    54 17 For AHI = 10 cutoff 82 73 27 12 36 27 For AHI = 5 cutoff 86 20 38 23 30 10 Identical results for AHI = 5 and AHI = 10 cutoffs 92 80 21 14 – – Tablet used as placebo; CPAP arm was also present 122 73 24 12 36 – For AHI = 5 cutoff    55 – For AHI = 10 cutoff Summary  270 25 14 35 24 For AHI = 5 cutoff     50 14 For AHI = 10 cutoff 93 94 114 39 116 117 Oral appliances vs CPAP 6 2 Table 6 Randomized, crossover, CPAP vs oral appliance studies Reference N base appl AHI CPAP Comments 46 19 20 10 4 p 45 21 34 20 11 OA preferred 50 20 25 14 4 65% preferred OA, 30% preferred CPAP 84 20 18 14 4 “Patients identified oral appliance as being easier to use” 85 48 31 15 8 “Neither treatment was significantly preferred by patients” 88 24 22 8 3 “...17 out of the 21 subjects who completed both arms of the study preferred the MAS” 92 80 21 14 5 “Although subjects reported that CPAP was the most difficult treatment to use, they felt that it was the most effective and overall preferred it to the MAS, which was in turn preferred to placebo” Summary  232 24 14 6 Oral appliance preferred overall 87 102 2 87 102 We conclude therefore that CPAP is more effective than oral appliances in reducing AHI, but despite this, most patients prefer oral appliances, undoubtedly because they find them to be less cumbersome than CPAP. Oral appliances vs other treatments 21 53 59 64 65 68 77 79 89 90 100 7 base appl Table 7 Studies comparing oral appliances to treatments other than CPAP Reference N AHI Comments Base Appl Comp 53 23 4 3.5 0.8 Parallel groups; OA=MAA with max protrusion, comp=MAA with 70% of maximum protrusion, but double inter-incisal opening; baseline AHI = 7 for comp group 59 41 18 6 10 Parallel groups; OA=MAA, comp=UPPP; prospective, randomized, baseline AHI = 20 for UPPP group; results at 12 months 64 37 26 17 11 Single group; OA=MAA with 2 mm protrusion, comp = 6 mm protrusion; ODI4 recorded 65 5 50 30 44 Single group; OA=MAA, comp=TRD; only 5/8 patients agreed to try TRD 65 2 47 35 57 Single group; comp=SPL; only 2/8 patients agreed to try SPL 68 24 23 9 8 Crossover, randomized; OA=MAA (Herbst), comp=monoblock 21 10 5 5 10 Parallel groups: OA=TRD, comp=somnoplasty; baseline RDI same for both groups 77 23 21 8 10 Crossover, randomized; OA=MAA with 4 mm inter-incisal opening, comp=MAA with 14 mm opening 79 72 18 7 14 Parallel groups, randomized; OA=MAA, comp=UPPP; baseline AHI for UPPP group = 20; results at 4 years 89 84 47 17 16 Parallel groups, randomized; OA=MAA with 50% protrusion, comp=MAA with 75% protrusion; baseline AHI for 75% group = 50; results at 6 months 90 55 16 6 6 Parallel groups, randomized; OA=MAA with 50% protrusion, comp=MAA with 75% protrusion; baseline AHI for 75% group = 19; results at 12 months 100 16 46 25 34 Crossover, prospective, randomized; OA=Herbst, comp=Twin Block; median AHIs reported Summary  392 26 11 12  Examination of the individual investigations reveals that when oral compliances are compared to each other, either two different appliances or the same appliance with different degrees of protrusion or opening—it is cleat that the efficacy (objective and subjective) is very much dependent on the type of appliance and the degree of advancement. This further emphasizes the point that oral appliance therapy should be carried out by a dentist with expertise in this field who is familiar with different types of appliances and can select the most appropriate one for the particular patient. There is no “best” appliance. The best one is that which is comfortable to the patient and achieves the desired efficacy. 59 79 21 121 Oral appliances for the treatment of snoring Although everyone can recognize snoring, it proved to be a very elusive entity to measure objectively. One can define the sound properties (i.e. frequency spectrum and intensity), relationship to breathing (i.e. waxing and waning sound, generally during inspiration), and measure this sound during sleep. However, subjective recognition of sound, which satisfies some pre-defined “snoring” criteria as de facto snoring depends very much on the listener. This is contrary to the case of apneas or even hypopneas, whose definition is independent of any subjective perception. These difficulties with the definition of snoring are the reasons why objective measurement of sound is seldom a routine part of polysomnography. However, snoring is the cardinal symptom of sleep apnea. In fact, it is frequently the only reason why these patients come to the sleep clinic in the first place. Consequently, when polysomnography does not reveal sleep apnea in these patients, the physician still has to deal with their snoring. Unfortunately, this is often ignored by physicians. The most frequent scenario is that a patient is referred to a sleep specialist because of snoring, polysomnography is carried out, no sleep apnea is found, the patient is reassured, advised to loose weight, stop smoking and drinking alcohol, embark on an exercise program, and discharged from the clinic. Sometimes this advice, dispensed in the form of preprinted sheets, is given also to non-obese non-smokers. Clearly, the patient leaves unhappy, the referring physician is dissatisfied with the help received from the specialist and nothing was accomplished to justify the expense incurred in the process of investigations. For apneic snorers, the problem is simpler because treatment with CPAP will abolish snoring. Non-apneic snorers without daytime symptoms do not tolerate CPAP well. Many of them will agree to try it, but the majority will stop using it after a short time (generally a few weeks to a few months). Oral appliances therefore constitute an attractive alternative for the treatment of snoring. In fact, they were originally invented precisely for that reason. 115 8 Table 8 Snoring Reference N Type Snoring measure Comments Base Appl 27 5 TRD   “Snoring decreased or completely disappeared” 28 12 MAA   “8/12 reported substantial reduction of sonorous sleeping 31 1 MAA   “After appliance insertion...immediate...reduction in snoring” 34 68 MAA 8.5 1.5 Snoring severity assessed subjectively (max score = 10); snoring eliminated in 42% 35 12 MAA   Snoring reduced, although never eliminated, in 79% 38 24 MAA 7.6  Snoring on a scale from 0 to 10; improvement also on a scale from 0 to 10—result = 4.3 42 51 MAA 9.4 8.2 No. of snores/min; snoring eliminated in 8/51, improved in 43/51 46 25 MAA   Snoring less than “moderate” in 19/25 pts 47 23 MAA   “...20/23 patients (87%) reported subjective improvement...in snoring” 49 23 TRD   “Visual analog scores of snoring...were also reduced significantly” in 6/23 (23%) subjects 53 23 MAA   “...loud snore duration was reduced from a median of 27.1 min to 11.4 min” 54 44 MAA   “Snoring was satisfactorily reduced in” 37/44 patients (84%) 57 15 MAA 193 20 Median snores/h given; snoring loudness and time spent snoring also improved 102 132 MAA   “Snoring was reported...to be satisfactorily controlled in 107 (81%)... 58 14 MAA   6/14—no snoring; 8/14—mild snoring 59 41 MAA 0.7 0.5 No. of snores/h of sleep at baseline and 12 months follow-up (NS) 60 75 MAA   “Dramatic reduction in the attributes of snoring was achieved” 66 112 MAA   76/112 (68%) snoring either eliminated or acceptable 68 24 MAA 50 33 No of snores/h sleep; results for Herbst appliance; 19/20 disturbed by snoring at baseline, vs 9/20 with appliance 21 10 TRD 11 3 Percent of time spent in loud snoring 69 39 MAA   “Time with snoring dropped significantly from 16.3% to 6.6%” 71 22 MAA   Snoring eliminated in 13/22, significantly reduced in 5/22; success rate = 18/22 (82%) 104 53 MAA   Questionnaire survey; 27/53 were still using the device at 1 year, and 22 were satisfied (42%) 105 21 MAA   Questionnaire survey; 22 patients fitted with appliance; 43% thought it reduced snoring, 48%—no benefit 102 126 MAA   Questionnaire survey; “80 out of 94 patients reported improvement in snoring” 73 22 MAA 59 24 No. of snores/h of sleep; subjective improvement as well 75 25 MAA 3.4 1.8 p 76 33 MAA   “19/33 had short-term satisfactory treatment results with the device” 72 28 MAA 402 242 p 82 73 MAA 366 207 p 86 16 MAA 3.1 2.6 p 79 32 MAA 0.7 0.5 p 80 26 MAA   “The patients and their bed partners thought that...snoring...improved...” 84 20 MAA 55 36 p 89 40 MAA 0.86 0.57 p 90 26 MAA   Comparison of two protrusions; results for 75% protrusion group; “problems with apneas and snoring...decreased by...79%...” 91 25 MAA   “...snoring...patients have benefited from oral appliance therapy and their spouses will testify to the same” 93 44 MAA   Subjective assessment; “on average, a mean reduction of 90% of the intensity of snoring was reported by the patients” 95 619 MAA   “It is estimated that 50% of the 619 snorers and sleep apnea patients had treatment success or subjective beneficial effects...” 96 11 MAA 240 75 Noise level measured; “10 out of 11 subjects had a significant reduction in snore noise sound level...” 97 20 MAA 9.0 6.8 p 106 110 MAA   Questionnaire survey; 37 out of 77 patients who returned questionnaire thought snoring was satisfactorily controlled 99 17 MAA 53 16 p 19 25 MAA   15/25 snoring markedly improved 100 16 MAA 144 64 Snores/h; however, VAS 0–10 scale–no difference 101 251 MAA   75% of 191 users of appliance reported control of snoring; 43% of non-users of appliance also thought snoring was controlled 115 53 MAA   Snoring was reported to be improved by 70% of the responding bed partners 86 86 75 100 8 9 21 9 9 Table 9 Studies with measurement of snoring Reference N Snoring measure Explanation of snoring measurement Percent change Base Appl 34 68 8.5 1.5 Visual analogue scale 0–10 −82 42 51 9.4 8.2 Number of snores/min −13 57 15 193 20 Number of snores/h −90 59 41 0.7 0.5 Number of snores/h −29 68 24 50 33 Number of snores/h −34 21 10 11 3 Percent of sleep time spent in loud snoring −73 73 22 59 24 Number of snores/h −59 75 25 3.4 1.8 Nights/per week with disturbing snoring −47 72 28 402 242 Number of snores/h −40 82 73 366 207 Number of snores/h −43 86 16 3.1 2.6 Nights/per week with disturbing snoring −16 79 32 0.7 0.5 Minutes of snoring/h of sleep −29 84 20 55 36 Snoring epochs/h of sleep −35 89 40 0.86 0.57 Minutes of snoring/h of sleep −34 96 11 240 75 Noise level −69 97 20 9.0 6.8 Visual analogue scale 0–10 −24 99 17 53 16 Total snoring time −66 100 16 144 64 Number of snores/h of sleep −56 Summary  529    −45 Effect of oral appliances on daytime function In assessing the effect of oral appliances on sleep apnea syndrome, it is not sufficient to focus only on the apnea/hypopnea index or snoring. We must also demonstrate the effect of this treatment on daytime function, which is almost always compromised in patients with sleep apnea and sometimes in non-apneic snorers also. There are several tools used to assess daytime function, but there is little consistency in using these tools in investigations involving oral appliances. 10 Table 10 Functional assessment Reference N Test or question Result Comments Base Appl 11 14 Daytime function – – 14/14 reported improvement 25 7 Sleepiness – – Improved 26 44 Vigilance 0.5 0.4 p 27 5 Daytime sleepiness – – “Daytime somnolence was eliminated or diminished markedly” 28 12 Daytime somnolence – – “9/12 patients reported increased alertness and/or reduction in daytime sleepiness” 34 63 Prevalence of daytime sleepiness – – “51% of these patients reported no more sleepiness with orthosis use” 35 12 Daytime sleepiness – – “Daytime sleepiness was improved...in all but two patients” 33 14 Symptom score (including sleepiness) 5.5 1.1 p 38 24 Sleepiness and improvement using 0–10 Likert scale 6.4 – Improvement on 0–10 Likert scale = 4.5 at 36 months 42 51 Patients tired; patients sleepy 44 30  44 30 No. of mistakes in vigilance test 7.6 3.7 p 45 21 EDS daytime symptoms 2.4 1.6 p 46 25 Prevalence of EDS 84% 40% p 47 23 Patients with EDS 23 20  49 14 EDS using VAS – – p 50 20 ESS 10.3 4.7 p 53 14 ESS 12 4.5 p 53 9 ESS 7 4 p 54 44 Patients with daytime sleepiness 44 34  58 14 Patients with moderate and severe daytime somnolence 10 0  59 41 Daytime sleepiness on 1–5 scale – – p 60 75 ESS 11 7 p 107 90 Quality of life (vitality+contentment+sleep) 129 94 Significant improvement compared to baseline; two parallel groups—OA vs UPPP; no difference in vitality and sleep 66 112 No. of patients “refreshed by sleep” – 66/114 “Most of the regular users had an improvement in their quality of sleep and day time somnolence...” 68 24 ESS 13.1 8.6 p 71 22 No. of patients whose sleepiness disappeared  17/22 “17 (85%) of 22 patients reported subjective improvement in excessive daytime sleepiness” 72 24 ESS 10.1 3.9 p 73 22 ESS 12 7.5 p 75 24 ESS 7.5 6.5 p 76 19 No. of patients reporting reduction in EDS  13/19  77 23 ESS 18 12 p 81 26 Questionnaire: EDS  1.61 Scale from −3 (maximum deterioration) to +3 (maximum improvement) 87 34 ESS 13 7.7 After 28 days, only 11 patients continued to wear MAA; initial ESS based on 34 patients, final—on 11 88 24 ESS 13.4 9.0 p 85 48 ESS 14 12 NS; randomized crossover vs CPAP; extensive tests of daytime function; “these results do not support these MRS devices as first-line treatment for sleepy patients with SAHS” 82 73 ESS 11 9 p p p 86 18 ESS 12.6 11.6 NS; randomized placebo-controlled crossover trial of apneic snorers 89 42 ESS 11.5 7.5 p 90 55 Questionnaire: EDS   n n 96 29 ESS 9.4 6.9 p 92 80 ESS 10.2 9.2 p 93 40 ESS 12.0 5.1 p 97 20 ESS 8.8 5.4 p 98 42 ESS 10 6 p 19 27 ESS 9 6 p 100 16 ESS 10 8 Median values 101 161 ESS 11 7 In users of OA; in 90 non-users—ESS fell from 11.1 to 8.1 115 67 Concentration, energy levels, sleep quality, ESS 9.7 – ESS given; 29–59% of responders reported improvement 122 73 ESS and full battery of neuropsychological measures 5.0 4.2 Total score of all self-report measures given; prospective, randomized, placebo-appliance-controlled 4 weeks study 11 19 53 98 100 Table 11 Functional assessment using ESS Reference N ESS Comments Base Appl 50 20 10.3 4.7 p 53 14 12 4.5 p 53 9 7 4 p 60 75 11 7 p 68 24 13.1 8.6 p 72 24 10.1 3.9 p 73 22 12 7.5 p 75 24 7.5 6.5 p 77 23 18 12 p 87 34 13 7.7 After 28 days, only 11 patients continued to wear MAA; initial ESS based on 34 patients, final ESS—on 11 88 24 13.4 9.0 p 85 48 14 12 NS; randomized crossover vs CPAP; extensive tests of daytime function; “these results do not support these MRS devices as first-line treatment for sleepy patients with SAHS” 82 73 11 9 p p p 86 18 12.6 11.6 NS; randomized placebo-controlled crossover trial of apneic snorers 89 42 11.5 7.5 p n n 96 29 9.4 6.9 p 92 80 10.2 9.2 p 93 40 12.0 5.1 p 97 20 8.8 5.4 p 98 42 10 6 p 19 27 9 6 p 100 16 10 8 Median values 101 161 11 7 Result for users of OA; in 90 non-users—ESS fell from 11.1 to 8.1 122 73 9.1 7.1 Prospective, randomized, placebo-appliance-controlled 4 weeks study Summary  854 11.2 7.8 19 53 98 100 85 86 85 75 86 75 86 In all other randomized, crossover, controlled studies there was a statistically significant improvement in the ESS, but not in other subjective measures of daytime performance. In fact, none of the studies demonstrated a significant improvement in all of the subjective outcomes studied. This is not surprising because almost all studies comparing placebo treatment with active treatment, no matter what it is, always demonstrate a significant placebo effect. 122 107 The effect of oral appliances on daytime function was not studied as fully and extensively as for CPAP. For example, there are no studies comparing driving simulator performance in patients treated with oral appliance, no studies comparing multiple sleep latency or maintenance of wakefulness. Recognizing the limited nature of the data—the conclusion from all of the investigations taken as a group must be that oral appliances improve daytime function, although they are not necessarily superior or consistently preferred than other treatments such as CPAP and UPPP. Effect of oral appliances on vascular disease Numerous investigations examined the relationship between sleep apnea and vascular events, such as coronary artery disease, hypertension, and cerebro-vascular disease. Fewer, but still many investigations were carried out to examine the effect of the treatment of sleep apnea with CPAP on changes in these conditions. 113 92 126 99 There is not enough evidence at the present time to draw any conclusions regarding the effect of oral appliance therapy on vascular disease. This remains a very interesting area of investigation. Given the differences in intra-thoracic pressure as a consequence of CPAP vs oral appliance, it is possible that results obtained with oral appliances therapy will be different from those obtained with positive pressure therapy. Side effects 101 102 106 110 12 Table 12 Patient reported side effects of oral appliances Side effect Percent of patients Reference reporting maximum percent Difficulty in chewing 11–19 101 Excessive salivation 9–60 106 Dry mouth 14–86 73 Tooth discomfort 11–59 73 Tongue discomfort 6–8 101 Jaw discomfort 8–41 73 Gum discomfort 1–2 101 Headache 2–27 89 Occlusive changes 41 76 TMJ pain 37 102 Masseter muscle pain 45 66 No side effects at all 100 39 95 101 39 13 78 118 127 118 119 Table 13 Dental effects: overjet and overbite Reference N F/U (months) Overjet Overbite Comments Base F/U Base F/U 39 19 13 4.0 −3.0 2.9 6.3 Herbst appliance 108 32 24 4.5 4.1 3.6 3.5  71 22 6 5.97 1.08 3.97 −8.01 After correction for magnification error 109 87 30 4.25 3.19 4.09 3.07 Effects evident already at 6 months 73 22 14 3.3 3.1 4.0 3.6 Median results at follow-up 110 47 28 3.9 3.6 3.2 2.8 Significantly larger changes compared to reference group 110 28 31 4.5 3.9 3.8 3.3 Ibid 81 34 30 4.4 3.1 3.6 2.5  111 30 48 3.5 3.1 4.3 3.8 NS; compared to UPPP 112 20 30 3.84 2.63 4.43 2.61 Effects evident at 6 months 90 29 12 – – 2.5 2.4 NS; for 50% protrusion; same for 75% protrusion 118 187 60 3.5 3.0 3.0 2.80 Median values; overbite change NS; orthodontic side effect increase with treatment time and more frequent use 119 31 89 2.12 0.45 2.7 0.46 70 patients followed-up for 7.4 years; measurements made from models; “unfavorable change” group 119 10 89 2.75 2.9 4.45 3.87 As above; “no change” group 119 29 89 3.95 2.72 4.47 2.52 As above; “favorable change” group 127 67 36 – – – – Only changes, but not baseline values in overjet and overbite are given (−0.8 and −0.6, respectively over 3 years); small but significant reductions observed mainly during the first year Summary  389 39 4.0 2.6   73 118  418 37   3.7 2.4 Compliance Compliance with oral appliances depends strictly on the balance between the perception of benefit and side effects. Most patients treated with oral appliances have relatively mild sleep apnea and relatively few daytime symptoms; the main reason for treatment was snoring. Consequently, the perception of benefit is generally that of the bed partner, whereas the side effects are experienced by the wearer of the appliance. This is why the assessment of compliance is a complex issue. In some cases, although the appliance is quite comfortable, the patient may stop wearing it if the bed partner is no longer present or no longer complains of snoring. 14 49 Table 14 Compliance with oral appliances Reference N F/U (months) Compliance (%) 34 71 7 71–75 35 24 12 4–5 38 24 36 50–75 39 19 24 68–93 47 29 41 55–70 49 23 6 21 103 191 31 52–76 107 45 12 82 66 173 9 45–70 70 256 31 90 71 22 6 100 76 33 62 58 102 166 22 42–56 79 45 48 62 81 86 18–24 30–53 89 74 12 72–76 106 110 22 40–57 95 630 12 75–76 101 544 68 30–64 115 92 3 68 118 450 60 56 Summary  3,107 33 56–68 101 Pooled data summarizing all 21 reviewed studies involving 3,107 patients, showed that at the end of 33 months, 56–68% of them continued to wear the appliance. Conclusions Oral appliances used to date constitute a relatively heterogeneous group of devices for the treatment of sleep apnea and non-apneic snoring. It is this heterogeneity, which partly accounts for the variability in their benefit and side effects. Another reason for variability is the diverse methodology employed in different studies. The evidence available at present indicates that oral appliances successfully “cure” mild-to-moderate sleep apnea in 40–50% of patients, and significantly improve it in additional 10–20%. They reduce, but do not eliminate snoring. Side effects are common, but are relatively minor. Provided that the appliances are constructed by qualified dentists, 50–70% of patients continue to use them for several years. Their effectiveness is inferior to CPAP. It is similar to surgical procedures, but these are invasive, (although not particularly dangerous) and irreversible. The effect of oral appliances on the vascular consequences of sleep apnea is not known. 124 125 An important issue, not addressed in this review, is the underuse of oral appliances currently. This is due in part to the lack of qualified dentists working in this area and in part to reimbursement policies. At present, the majority of government-sponsored and private health care providers will cover (fully or partially) the cost of CPAP, whereas very few, if any, health care plans will cover the cost of oral appliances. Considering that this treatment approach is the only non-invasive alternative to CPAP, it is important to continue to lobby health care providers to enable this treatment for qualified patients.