SystematicReviewsof Efficacyof TMD Treatment

James Fricton DDS, MS Professor University of Minnesota School of Dentistry HealthPartners Research Foundation Minnesota Head & Neck Pain Clinic

The Translation of Scientific Evidence into Successful Management of TMD Patients

Encourage clinicians to use of treatments that work and reduce use of treatments/ tests that do not work. Encourage clinicians to understand factors that contribute to treatment failure Identify the risk/ benefit ratio and minimize adverse events Insurers using EBC in decisions to cover a particular treatment or not Encourage RCT studies to be done on new treatments and tests and develop a high standard for evaluating new treatments by FDA.

QuestionsaboutTMDTreatments
What treatments have an active therapeutic effect beyond placebo? How well does a treatment work compared to another treatment or no treatment? What patient characteristics or diagnostic subtype does the treatment work best with? What are the risks/ adverse events related to treatment and do the benefits outweigh the risks? What factors contribute to delayed healing and recovery

Page 1

ReviewingtheTMDscientificliterature
Clinicians are faced a confusing array of available literature if they choose to make evidence-based clinical decisions 44 or more different TMD treatments with over 150 clinical trials with diversity in;
Study designs Treatment techniques Study populations Outcome measures Success rates

MethodsforSystematicReviewof TMDTreatment Identify either meta-analysis of RCT or treatments with at least one randomized clinical trial (RCTs) Compare the outcomes and characteristics of RCTs Evaluate the quality of methods used in each RCT Capture results qualitatively and quantitatively Conduct meta-analysis and Forrest Plot when possible

Acknowledgements
Contributors James Fricton, D.D.S., M.S. Edward Wright D.D.S., M.S. John Look, D.D.S., Ph.D. Robert Rosenbaum D.M.D. Hong Chen D.D.S. Karen Decker R.P.T. Maureen Lang D.D.S., M.S. James Luderitz D.D.S., M.S. Mariona Mulet D.D.S., M.S. Francisco Alencar D.D.S.,M.S. Wei Ouyang D.D.S., M.S. Gary Anderson D.D.S.,M.S. Consultants Kathy Robbins, B.A. Informatics Richard Niederman, D.D.S, Ph.D. Wenjun Kang M.S. Informatics Sponsors American Academy of Orofacial Pain NIDCRs TMJ Implant Registry and Repository NIH-NIDCR Contract No. N01-DE-22635 NIH-NIDCR R01 No. DE11252-03 University of Minnesota School of Dentistry

Page 2

Search of the Literature for RCTs

A MEDLINE search strategy was developed to include the years 1966-2006 and implemented on the PubMed interface for MEDLINE at the US National Library of Medicine and include all TMD terms (http://www.ncbi.nlm.nih.gov/PubMed/). Based on the recommendations of the US Agency for Health Care Policy and Research and the Centre for Evidence-based Medicine (http://cebm.jr2.ox.ac.uk/doc/levels.html) Manual searches of references

Critical Assessment of Method Quality

21 Criteria from CONSORT (Consolidation of the Standards of Reporting Trials, 2001) Operationally defined and tested for reliability (intraclass correlation coefficient for inter-rater reliability was 0.85) Applied to each TMD RCT Quantitative and qualitative review
Reference- Fricton JR, Ouyang W, Nixdorf DR, Schiffman EL, Velly AM, Look JO. Critical appraisal of methods used in randomized controlled trials of treatments for temporomandibular disorders. J Orofac Pain. 2010 Spring;24(2):139-51.

TMD Treatments Reviewed

Splints and occlusal treatments (55 RCTs)* Stabilization (hard and soft), repositioning and anterior splints, occlusal adjustment, restorative dentistry, and functional orthodontic splints Physical medicine and PT modalities, stretching, posture, exercise (45 RCTs) conditioning Therapeutic Injections and Trigger point injections, Botox injections, acupuncture (39 RCTs) TMJ joint injections, acupuncture Psychological therapies Cognitive-behavioral treatment, (24 RCTs) Biofeedback, Relaxation Pharmacologic therapy NSAIDS, tricyclics, SSRIs, muscle (44 RCTs) relaxants, and opioids TMJ surgery (7 RCTs) TMJ arthroscopic and arthroplasty
* Fricton, J, Look, JO, Wright, E, Alencar, F, Chen, H, Lang, M, Ouyang, W, Velly, AM. Systematic Review of Intraoral Orthopedic Appliance for Temporomandibular Disorders: 51 RCTs Reviewed. J Orofacial Pain 24:237-54.2010.

Page 3

Splint Therapy
Splints have been suggested to provide protection to muscles and joints and help reduce oral habits
Type of Splint (7 RCTs: Quality=0.51) Hard Stabilization Splints Soft Splints Pain relief compared to placebo? 3+ 3=

1+

No placebo controlled RCTs conducted on repositioning splints, anterior bite plane, or other splints.

Forest plot from meta-analysis comparing active splints vs placebo splints (n=344)
Results show slight overall trend towards splint
Odds ratio and 95% confidence interval

Ekberg et al 1998, 1999 Raphael et al 2001 Ekberg et al 2003 Dao et al 1994 Rubinoff et al 1987 Wassell et al 2004

Favors placebo

Favors splint

Conclusion: Stabilization splints are better than placebo when used with more severe TMD patients and while sleeping at night.
Fricton, J, Look, JO, Wright, E, Alencar, F, Chen, H, Lang, M, Ouyang, W, Velly, AM. Systematic Review of Intraoral Orthopedic Appliance for Temporomandibular Disorders: 51 RCTs Reviewed. J Orofacial Pain 24:23754.2010.

Stabilization Splint
Design: Maxillaryormandibularfullcoverage Adjustment:evenposteriorcontactatclosure,anterior guidance,andcanineguidanceorgroupfunctioninlateral excursionswithnobalancingsidecontacts. Constructedtoguidedjawpositionandposturalrestposition (reclinedandsitting) Betterresultifitiscombinedothertreatmentmodalities(self care,exercise,behavioraltherapy) Worksbestinpatientswithhighlevelsofpainbutcanbeused withalllevelsofseverity

Page 4

Take Home: Stabilization Splint

Cantreatmuscle,jointpain,andheadache Effectiveevenwhenused onlyatnight Betterresultifitiscombinedothertreatment modalities(selfcare,exercise,behavioraltherapy) Worksbestinpatientswithhighlevelsofpainbut canbeusedwithalllevelsofseverity

Anterior Bite Plane Splint

Design: Amaxillaryofmandibularhardsplintallowingcontactof onlyoneofmoreanteriorteeth.Theposteriorteethdonotcontact. Othernames: NTIsplint,Anteriorjig,Lucajig,Hawleywith biteplaneoranteriordeprogrammer. SuggestedIndications: Headacheandmusclepain Eliminateproprioceptivefeedbackfromtheposteriorteeth Reduceoralhabitsandmuscleactivity

RCTs comparing anterior bite plane to stabilization splints

Author Shankland et al., 2001 Group TTH/ Migraine N 43 51 Treatment A: Mandibular fullcoverage occlusal splint B: NTI anterior bite splint Durati on 8 wks Outcome measure Greater than 85% reduction in migraine. % reduction in tension headache % reduction in headache intensity Subjective symptoms Anamnestic index Subjective symptoms Global improvement Range of motion Headache TMJ pain to palpation Jaw muscle tenderness Comfort Result B>A B>A B=A A>B A>B A>B A>B A=B A=B A=B A=B A=B

Magnusson et al., 2004

TMJD

14 14

A: Stabilization splint B: NTI splint

3 mos 6 mos 3 mos

Jokstad et al., 2005

TMJD

20 18

A: Stabilization splint B: NTI splint

Page 5

Take Home: Anterior Bite Plane

GoodresultsintreatingTMJDandheadache Efficacyequaltostabilizationsplint Betterresultsifitisusedincombinationwithother treatmentmodalities Itmaycauseanteriorbitechangesifwornfulltime Considerstabilizationsplintfirstforlowerrisk

How does occlusion relate to TMD?

1. TMDcancausemalocclusion 2. TMDtreatmentcancauseiatrogenic malocclusion 3. Malocclusion cancomplicateTMDtreatment 4. Occlusaltreatmentscanbeusedtotreat TMDandocclusalconsequences

Occlusal Consequences of TMD

TMDcanleadtomalocclusionbychangingthe positionofthemandiblerelativetothemaxilla including: Lateralpterygoidspasm TMJdegenerativejointdiseaseanddiskdisorder insomecases TMJhyperplasiaorhypoplasia Uncontrolledbruxismandtoothwear

Page 6

Iatrogenic Malocclusion from TMD Treatment

Malocclusionmayresult unintentionallyfromsomeTMD treatmentsfromchangingthepositionoftheteethorthe mandiblerelativetothemaxillaincluding; Partialcoveragesplintsthatintrudeteethandcause anteriororposterioropenbite Fulltimeuseofanteriorrepositioningsplintsthatcause anteriorprematuritiesandposterioropenbite Occlusalshiftsfromunstablejointsafterflatplanesplints ororthodonticscanresultinopenbiteorcrossbites

Partial coverage splints

Permanent posterior open bite from full time use of partial coverage posterior splint. Open bite due to anterior positioning of jaw and/or impaction of posterior teeth

Malocclusion as a contributing factor in TMD

In some cases, TMD is associated with malocclusion. The most commonly cited occlusal factors include; Loss of posterior support Unilateral prematurities Long slide in centric Non working interferences Unilateral posterior lingual crossbite Anterior open bite Most occlusal factors are amplified by oral habits

Page 7

Occlusal dysharmony is only an associated factor in many cross sectional and longitudinal studies

(NS, P.05)

(NS, P.05)

(NS, P.05)

Occlusal Therapy
Occlusal treatmentsuchasocclusal adjustment,restorativedentistryand orthodontics(9RCTs)hasbeen suggestedtoprovideocclusal stability forthemusclesandjointandreduce eccentricforces
Type of Occlusal Treatment (4 RCTs: Quality=0.47) Occlusal Adjustment Restorative Dentistry (On-lays) Pain relief compared to placebo? 1 study + 2 studies =

1 study +

No RCTs conducted on orthodontics, orthognathic surgery, full crowns, or other occlusal treatments.

Forest plot from meta-analysis comparing occlusal adjustment vs placebo adjustment for TMD treatment (n=182) Results shows no overall difference between groups
Odds ratio and 95% confidence interval

Forssel et al 1986 Tsolka et al 1992 Karppinen et al 1999

Favors placebo

Favors Occlusal Adjustment

Fricton, J. Current Evidence Providing Clarity in Management of Temporomandibular Disorders: A Systematic Review of Randomized Clinical Trials for Intra-oral Appliances and Occlusal Therapies. Journal of Evidence based Dentistry. March issue, Vol 6, issue 1, pp 48-52, 2006

Page 8

Take Home: Occlusal Treatments

Occlusal adjustmentnobetterthanplaceboadjustmentin treatingTMDpain. Occlusal treatmentshouldbereservedforcaseswhen; Occlusionisthecomplainti.e.uncomfortablebite afteroralhabitsaretreated. Afterrestorative,orthodontics,orotherocclusal treatmenttoensureocclusioniscomfortableand functional Aestheticandfunctionalreasons

What Other TMD Treatments Work?

Splints and occlusal treatments (55 RCTs) Stabilization (hard and soft), repositioning and anterior splints, occlusal adjustment, restorative dentistry, and functional orthodontic splints Physical medicine and PT modalities, stretching, posture, exercise (45 RCTs) isometrics, functional, conditioning Therapeutic Injections and Trigger point injections, Botox injections, acupuncture (39 RCTs) TMJ joint injections, acupuncture Psychological therapies Cognitive-behavioral treatment, (24 RCTs) Biofeedback, Relaxation Pharmacologic therapy NSAIDS, Acetominophen, tricyclics, (44 RCTs) SSRIs, muscle relaxants, and opioids TMJ surgery (7 RCTs) TMJ arthroscopic and arthroplasty

Exercises for TMD

Exercisesaredesignedto: 1. improverangeofmotion 2. Reducemuscleandjointpain 3. Improvemusclerelaxation 4. Improvepostureandposturalhabits 5. Improvemusclefunction 6. Improvemusclestrengthandconditioning

Page 9

Therapeutic Exercises

Jaw exercise (13 RCTs) has been found to improve range of motion of muscles and joints, relax muscles, improve posture and encourage healing
Type of Exercise (5 RCTs: Quality=0.62) Stretching exercise Resistance exercise Posture training Pain relief compared to placebo? 2+ 1= 1+ 1+

Forest plot from meta-analysis comparing exercise vs placebo for TMD treatment (n=150) Results shows exercise over placebo
Odds ratio and 95% confidence interval

Burgess et al. 1988 Dall Arancio et al. 1993 Minakuchi et al. 2004 Shata et al. 2000

Favors placebo

Favors exercise

Conclusion: Exercise show greater improvement than placebo in treating TMD pain and headache. Stretching and posture exercise should be used in cases of myofascial pain and TMJ pain disorders with limited range of motion.
-Fricton, J, Velly, A. Ouyang W., Look, J. Does exercise therapy improve headache? A systematic review with meta-analysis. Current Pain & Headache Reports 13(6):413-419, 2009.

TMD Treatments Reviewed

Splints (42 RCTs) Physical medicine and exercise (52 RCTs) Therapeutic Injections and acupuncture (21 RCTs) Behavioral and Psychological therapies (21 RCTs) Pharmacologic therapy (44 RCTs) stabilization and repositioning appliances, hard and soft PT modalities, stretching, function, posture, conditioning Trigger point injections, Botox injections, TMJ joint injections, acupuncture Cognitive-behavioral treatment, Biofeedback, Relaxation NSAIDS, acetominophen, tricyclics, SSRIs, muscle relaxants, benzodiazepines, corticosteroids, glucosamine/ chrondroitin, and opioids

Page 10

Behavioral and Psychological Treatment for TMD Summary of meta-analysis of 24 RCTs

Treatment Relaxation (11 RCTs) Cognitive behavioral treatment (8 RCT) Biofeedback (9 RCT) +++ Efficacy Comments * Moderate consistent benefit for headache and +++ TMJD pain +++
Moderate consistent benefit for TMJD pain additive effect to biofeedback, relaxation, occlusal

appliance and rehabilitation therapies as part of a multi-disciplinary treatment.

Moderate consistent effect for decreasing

headache and TMJD pain.

similar efficacy to splints, physical therapy, and

medical interventions over a 13 month,

long-term maintenance of improvement.

Strength of evidence: +++= > 4 positive RCTs, ++= 2 to 4 positive RCTs + =1 positive RCT, += conflicting evidence, - = negative RCTs, NA= no RCTs conducted

Cognitive Behavioral Therapy

CBTteachespatientstorelax muscles,reducestrainto musclesandjoints,help reduceoralhabits,and encouragehealing
Type of CBT compared to placebo (9 RCTs: Quality=0.54) Relaxation Training (5 RCTs) Biofeedback (3 RCTs) Behavioral training for oral habits (1 RCTs) Pain relief compared to placebo? 4+ 1= 2+ 1= 1+

Forest plot from meta-analysis comparing CBT vs placebo for TMD treatment (n=633)
Odds ratio and 95% confidence interval

Bussone et al. 1998 Fichtel et al. 2004 Larsson et al. 2005 Loew et al. 2000 Wahlund et al. 2003

Favors placebo

Favors CBT

Conclusion: Cognitive behavioral treatments including oral habit instruction, relaxation, or biofeedback should be considered for TMD patients with self reported day or night oral habits or objective indications of them, anxiety, stress, feeling hurried as contributing factors.

Page 11

TMD Treatments Reviewed

Splints (42 RCTs) Physical medicine and exercise (52 RCTs) Therapeutic Injections and acupuncture (21 RCTs)

stabilization and repositioning appliances, hard and soft PT modalities, stretching, function, posture, conditioning Trigger point injections, Botox injections, TMJ joint injections, acupuncture

Psychological therapies (21 RCTs) Cognitive-behavioral treatment, Biofeedback, Relaxation Pharmacologic therapy (44 RCTs) NSAIDS, acetominophen, tricyclics, SSRIs, muscle relaxants, benzodiazepines, corticosteroids, glucosamine/ chrondroitin, and opioids

Pharmacological Agents for TMJD: meta-analysis of 44 RCTs

Treatment NSAIDs and acetominophen (13 RCTs) Tricyclic antidepressants (11 RCTs) SSRIs (8 RCTs) Muscle Relaxants (cyclobenzaprine and tizanadine) (3 RCTs) Benzodiazepines (3 RCTs) +
modest evidence for a slight effect overall for

Efficacy* +++

Comments
Consistent evidence for short-term efficacy of

reducing mild to moderate TMJD pain and tension type headache +++
Consistent evidence for TMJD pain, but their

side effects can be a problem.

weak evidence for use with TMJD or tension

++

type headache
Some evidence supporting use but evidence is

lacking for their mechanism of action, their relative efficacy, and their indications

TMJD pain.

Strength of evidence: +++ = > 4 positive RCTs, ++= 2 to 4 positive RCTs + =1 positive RCT, +- = conflicting evidence, - = negative RCTs, NA= no RCTs conducted

Pharmacological Agents for TMJD: metaanalysis of 44 RCTs

Treatment Triptans (2 RCTs) Glucosamine and chondroitin sulfate (2 RCTs) Efficacy* Comments +
insufficient evidence for the use in reducing

TMJD pain or tension-type headache.

more beneficial than placebo for osteoarthritis at least equal to ibuprofen in terms of pain

reduction
slower onset for relief than NSAIDs but also

fewer side effects Corticosteroids (0 NA RCTs) Opioids (2 RCTs) +

Strong anti-inflammatory agent but no evidence

to make recommendation for the use in TMJD pain

strong analgesic for moderate to severe acute

pain but have insufficient evidence for the use in chronic TMJD pain or headache
Strength of evidence: +++ = > 4 positive RCTs, ++= 2 to 4 positive RCTs + =1 positive RCT, += conflicting evidence, - = negative RCTs, NA= no RCTs conducted

Page 12

Forest plot from meta-analysis comparing NSAIDs vs Acetominophen for TMJD/ headache pain (n=1434)
Odds ratio and 95% confidence interval

Schachtel et al., 1996 and Mehlisch et al., 1998 Packman et al. 2000 Steiner and Lange 1998

Favors Acetominophen

Favors NSAID

Conclusion: Plot shows a statistically significant net benefit (P < 0.01) associated with single oral doses of the nonsteroidal anti-inflammatories, ibuprofen or ketoprofen, when compared to acetaminophen

Forest plot from meta-analysis comparing Tricyclics vs Placebo for TMJD/ headache pain (n=484)
Odds ratio and 95% confidence interval

Bendtsen et al., 1996 Gobel et al., 1994 Holroyd et al., 2001 Langemark et al. 1990 Pfaffenrath et al. 1994

Favors Placebo

Favors Tricyclic

Conclusion: there is an overall trend towards showing favorable effects of the tricyclics compared to placebo (P = 0.368).

Take Home: Medications

NSAID,tricylics,andmusclerelaxantsimprovemuscle,joint pain,andheadache Canhaveadverseeventsifusedlongterm(e.g.GI,rebound pain) Betterresultif usedshorttermandcombinedother treatmentmodalities(selfcare,exercise,behavioraltherapy) PersonalExperience:Clonazepam(0.5mgHS)and cyclobenzaprine(10mghs)workswellinpatientswithhigh levelsofpain,anxiety,andnocturnalhabits

Page 13

Analgesic Abuse Headache I feel a lot better since I ran out of those pills you gave me.

TakeHome:TheNeedforIntegrative Care
What treatments have an active therapeutic effect beyond placebo? Splints, Exercise, Medication, and Behavioral therapy all have significant effects. They have a synergistic effect if used together in a multimodal approach to treatment Thus, use a team with complex patients Establish a problem list and treatment plan upfront

Page 14

Developmentofthe InformaticsPlatformfor PracticeBasedNetworks

Asecurewebbasedintegratedresearchinformationsystem

(IRIS)thatintegratesinvestigators,staff,subjects,andproviders toconductpracticebasedresearch
SponsoredbyNIH/NINRRC201194201,Jacko PIand

NIH/NIDCRN0122635,FrictonPI
Usedbyassociationsand providergroupstobetterunderstand

theirclinicalpractices,theirpatients,andtoextendtheircare intothepatientslife.

NetworkPortals
InvestigatorPortal

SubjectPortal

PractitionerPortal

PublicPortal

New approach to healthcare Health providers are informed by each person's unique clinical, genetic, and personal characteristics Allows individualized care based on these factors Predict susceptibility and course of disease, improve treatment outcomes, and reduce adverse events

Page 15

A New Book for Patients. Available at

Amazon, Barnes& Nobles, Goodreads, others.

g{t~

Page 16