Temporomandibular Joint Disorders
Conditions
Brief summary
The purpose of this study is to determine whether the combination of cognitive-behavioral treatment and nortriptyline are more effective than each treatment alone in reducing the pain and disability associated with TMD.
Detailed description
This is a randomized, controlled trial evaluating pharmacological (nortriptyline vs. active placebo - benztropine) and psychological (cognitive-behavioral therapy vs. disease education) treatments for pain and disability due to temporomandibular joint disorder (TMD). Patients 18 to 65 years old meeting RDC criteria for TMD and other eligibility criteria complete a 3-week baseline monitoring phase prior to randomization. Active treatment consists of weekly visits for 8 week, then maintenance treatment for 6 months. Outcome measures include pain, physical and psychosocial function and are assessed at post-treatment, 3-months, and 6-months
Interventions
Nortriptyline will be titrated up from 25 mg qhs to a maximum dose of 150 mg qhs based on treatment response and side effect profile.
Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile.
Six in-person, individual sessions of cognitive-behavioral therapy for pain management include relaxation training, pain coping skills training, cognitive therapy for negative and dysfunctional thoughts, and diaries for monitoring relaxation, goals, and negative thinking.
Six in-person, individual sessions of temporomandibular joint disorder (TMD) disease management (MGT) that include information about the jaw and good oral habits, diet, sleep, and general stress management.
Sponsors
Study design
Eligibility
Inclusion criteria
Inclusion: * Age \>= 18 and \<= 65 * Pain \>= 3 months duration due to temporomandibular joint disorder * Pain due to TMD is primary if other pain conditions present Exclusion: * Continuous, chronic painful non-reducing disc displacement of TMJ and patient can't open mouth * Unstable or acute severe pain from another pain condition * Patient is pregnant * Presence of a medical condition that contraindicates nortriptyline: angle-closure glaucoma,symptomatic orthosis * EKG: first degree heart block or QTc \> 450 msec * Unstable angina or a history of a myocardial infarction within the past 3 months * Current treatment with an antidepressant which cannot be withdrawn * Current use of a medication that interacts with nortriptyline to raise blood levels, such as selective serotonin reuptake inhibitors (e.g.,paroxetine), systemic anti-fungal agents (fluconazole), antiarrhythmics (e.g., quinidine), antipsychotics (e.g., haloperidol), and antibiotics (e.g., erythromycin). * Presence of dementia, psychosis or other disorder of cognition that impairs ability to participate in minimal contact intervention * Beck Depression Inventory (BDI) score \>= 35 OR BDI Item #9 (suicide item) is scored \> 1 * Patient has a terminal illness with a life expectancy of less than six months * History of arthrotomy of temporomandibular joint * History of allergic reaction to nortriptyline or benztropine * History of a therapeutic trial with nortriptyline (dose \>= 100 mg for at least 3 weeks)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain | baseline, post-treatment, 3 months, 6 months | 0 (no pain) to 10 (pain as bad as could be) rating of average pain during the past week; higher scores indicate greater pain |
| Change in Pain-related Interference | baseline, post-treatment, 3 months, 6 months | Multidimensional Pain Inventory: Pain interference subscale score; average score computed from 12 items rated on scale from 0=no interference to 6=extreme interference; higher scores indicate greater pain-related interference |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Pain | baseline, post-treatment, 3 months, 6 months | 0 (no pain) to 10 (pain as bad as could be) rating of worst pain during the past week |
| Mental Health as Assessed by the Short Form 36 Healthy Survey | baseline, post-treatment, 3 months, 6 months | The Mental Health Component score from the Short Form (36) Health Survey, which is a 36-item, patient-reported survey of patient health. The mental health component score is calculated from responses to the general health, mental health, vitality, physical and emotional role limitations, and social functioning subscales, with higher scores indicating better mental health. The scale ranges from zero (equivalent to maximum disability) to 100 (no disability). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nortriptyline Oral Capsule/CBT Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT. | 41 |
| Benztropine Oral Product/CBT Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT. | 38 |
| Nortriptyline Oral Capsule/Disease MGT Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management. | 37 |
| Benztropine Oral Product/Disease MGT Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management. | 24 |
| Total | 140 |
Baseline characteristics
| Characteristic | Nortriptyline Oral Capsule/CBT | Benztropine Oral Product/CBT | Nortriptyline Oral Capsule/Disease MGT | Benztropine Oral Product/Disease MGT | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.7 years STANDARD_DEVIATION 12 | 38.4 years STANDARD_DEVIATION 12.5 | 37.2 years STANDARD_DEVIATION 11.5 | 33.3 years STANDARD_DEVIATION 11.3 | 36.4 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 41 participants | 38 participants | 37 participants | 24 participants | 140 participants |
| Sex: Female, Male Female | 31 Participants | 29 Participants | 28 Participants | 17 Participants | 105 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 9 Participants | 7 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 38 | 0 / 37 | 0 / 24 |
| other Total, other adverse events | 32 / 41 | 24 / 38 | 21 / 37 | 15 / 24 |
| serious Total, serious adverse events | 0 / 41 | 0 / 38 | 0 / 37 | 0 / 24 |
Outcome results
Average Pain
0 (no pain) to 10 (pain as bad as could be) rating of average pain during the past week; higher scores indicate greater pain
Time frame: baseline, post-treatment, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nortriptyline Oral Capsule/CBT | Average Pain | post treatment | 2.8 units on a scale | Standard Deviation 2.6 |
| Nortriptyline Oral Capsule/CBT | Average Pain | 3 months | 2.1 units on a scale | Standard Deviation 1.6 |
| Nortriptyline Oral Capsule/CBT | Average Pain | baseline | 4.7 units on a scale | Standard Deviation 2.2 |
| Nortriptyline Oral Capsule/CBT | Average Pain | 6 months | 2.0 units on a scale | Standard Deviation 1.7 |
| Benztropine Oral Product/CBT | Average Pain | baseline | 4.4 units on a scale | Standard Deviation 2.1 |
| Benztropine Oral Product/CBT | Average Pain | post treatment | 2.7 units on a scale | Standard Deviation 2.1 |
| Benztropine Oral Product/CBT | Average Pain | 6 months | 2.0 units on a scale | Standard Deviation 2.1 |
| Benztropine Oral Product/CBT | Average Pain | 3 months | 2.4 units on a scale | Standard Deviation 2.2 |
| Nortriptyline Oral Capsule/Disease MGT | Average Pain | baseline | 4.5 units on a scale | Standard Deviation 2.2 |
| Nortriptyline Oral Capsule/Disease MGT | Average Pain | 3 months | 2.2 units on a scale | Standard Deviation 2.1 |
| Nortriptyline Oral Capsule/Disease MGT | Average Pain | 6 months | 1.4 units on a scale | Standard Deviation 1.6 |
| Nortriptyline Oral Capsule/Disease MGT | Average Pain | post treatment | 2.0 units on a scale | Standard Deviation 1.4 |
| Benztropine Oral Product/Disease MGT | Average Pain | 6 months | 2.2 units on a scale | Standard Deviation 2.5 |
| Benztropine Oral Product/Disease MGT | Average Pain | post treatment | 2.8 units on a scale | Standard Deviation 2.1 |
| Benztropine Oral Product/Disease MGT | Average Pain | 3 months | 2.5 units on a scale | Standard Deviation 2.1 |
| Benztropine Oral Product/Disease MGT | Average Pain | baseline | 5.0 units on a scale | Standard Deviation 1.8 |
Change in Pain-related Interference
Multidimensional Pain Inventory: Pain interference subscale score; average score computed from 12 items rated on scale from 0=no interference to 6=extreme interference; higher scores indicate greater pain-related interference
Time frame: baseline, post-treatment, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nortriptyline Oral Capsule/CBT | Change in Pain-related Interference | Change in score from baseline to post-treatment | 0.9 Change in scores on a scale | Standard Deviation 0.9 |
| Nortriptyline Oral Capsule/CBT | Change in Pain-related Interference | Change in score from baseline to 6 months | 0.8 Change in scores on a scale | Standard Deviation 0.8 |
| Nortriptyline Oral Capsule/CBT | Change in Pain-related Interference | Change in score from baseline to 3 months | 0.8 Change in scores on a scale | Standard Deviation 0.9 |
| Benztropine Oral Product/CBT | Change in Pain-related Interference | Change in score from baseline to post-treatment | 0.5 Change in scores on a scale | Standard Deviation 0.9 |
| Benztropine Oral Product/CBT | Change in Pain-related Interference | Change in score from baseline to 6 months | 0.7 Change in scores on a scale | Standard Deviation 1.2 |
| Benztropine Oral Product/CBT | Change in Pain-related Interference | Change in score from baseline to 3 months | 0.8 Change in scores on a scale | Standard Deviation 0.9 |
| Nortriptyline Oral Capsule/Disease MGT | Change in Pain-related Interference | Change in score from baseline to 3 months | 1.0 Change in scores on a scale | Standard Deviation 0.9 |
| Nortriptyline Oral Capsule/Disease MGT | Change in Pain-related Interference | Change in score from baseline to post-treatment | 0.5 Change in scores on a scale | Standard Deviation 0.7 |
| Nortriptyline Oral Capsule/Disease MGT | Change in Pain-related Interference | Change in score from baseline to 6 months | 0.7 Change in scores on a scale | Standard Deviation 0.8 |
| Benztropine Oral Product/Disease MGT | Change in Pain-related Interference | Change in score from baseline to post-treatment | 1.0 Change in scores on a scale | Standard Deviation 0.9 |
| Benztropine Oral Product/Disease MGT | Change in Pain-related Interference | Change in score from baseline to 6 months | 0.8 Change in scores on a scale | Standard Deviation 1.1 |
| Benztropine Oral Product/Disease MGT | Change in Pain-related Interference | Change in score from baseline to 3 months | 1.1 Change in scores on a scale | Standard Deviation 1.2 |
Mental Health as Assessed by the Short Form 36 Healthy Survey
The Mental Health Component score from the Short Form (36) Health Survey, which is a 36-item, patient-reported survey of patient health. The mental health component score is calculated from responses to the general health, mental health, vitality, physical and emotional role limitations, and social functioning subscales, with higher scores indicating better mental health. The scale ranges from zero (equivalent to maximum disability) to 100 (no disability).
Time frame: baseline, post-treatment, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nortriptyline Oral Capsule/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | baseline | 50.5 units on a scale | Standard Deviation 8.1 |
| Nortriptyline Oral Capsule/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | post-treatment | 50.8 units on a scale | Standard Deviation 10.4 |
| Nortriptyline Oral Capsule/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 3 months | 51.5 units on a scale | Standard Deviation 8.9 |
| Nortriptyline Oral Capsule/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 6 months | 52.2 units on a scale | Standard Deviation 7.8 |
| Benztropine Oral Product/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | post-treatment | 48.4 units on a scale | Standard Deviation 8.1 |
| Benztropine Oral Product/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 3 months | 50.2 units on a scale | Standard Deviation 8.7 |
| Benztropine Oral Product/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 6 months | 53.3 units on a scale | Standard Deviation 12.8 |
| Benztropine Oral Product/CBT | Mental Health as Assessed by the Short Form 36 Healthy Survey | baseline | 49.2 units on a scale | Standard Deviation 9.3 |
| Nortriptyline Oral Capsule/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 3 months | 52.6 units on a scale | Standard Deviation 10 |
| Nortriptyline Oral Capsule/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | post-treatment | 52.6 units on a scale | Standard Deviation 10 |
| Nortriptyline Oral Capsule/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 6 months | 52.3 units on a scale | Standard Deviation 7.2 |
| Nortriptyline Oral Capsule/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | baseline | 51.2 units on a scale | Standard Deviation 8.8 |
| Benztropine Oral Product/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 6 months | 53.6 units on a scale | Standard Deviation 7.3 |
| Benztropine Oral Product/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | post-treatment | 53.3 units on a scale | Standard Deviation 10.6 |
| Benztropine Oral Product/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | baseline | 48.0 units on a scale | Standard Deviation 8.9 |
| Benztropine Oral Product/Disease MGT | Mental Health as Assessed by the Short Form 36 Healthy Survey | 3 months | 53.8 units on a scale | Standard Deviation 10.1 |
Worst Pain
0 (no pain) to 10 (pain as bad as could be) rating of worst pain during the past week
Time frame: baseline, post-treatment, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nortriptyline Oral Capsule/CBT | Worst Pain | 3 months | 3.6 units on a scale | Standard Deviation 2.4 |
| Nortriptyline Oral Capsule/CBT | Worst Pain | 6 months | 3.3 units on a scale | Standard Deviation 2.1 |
| Nortriptyline Oral Capsule/CBT | Worst Pain | post-treatment | 4.0 units on a scale | Standard Deviation 2.9 |
| Nortriptyline Oral Capsule/CBT | Worst Pain | baseline | 6.7 units on a scale | Standard Deviation 2.3 |
| Benztropine Oral Product/CBT | Worst Pain | post-treatment | 4.1 units on a scale | Standard Deviation 2.8 |
| Benztropine Oral Product/CBT | Worst Pain | baseline | 6.1 units on a scale | Standard Deviation 2.2 |
| Benztropine Oral Product/CBT | Worst Pain | 3 months | 3.3 units on a scale | Standard Deviation 2.3 |
| Benztropine Oral Product/CBT | Worst Pain | 6 months | 3.1 units on a scale | Standard Deviation 2.7 |
| Nortriptyline Oral Capsule/Disease MGT | Worst Pain | 6 months | 2.7 units on a scale | Standard Deviation 2.2 |
| Nortriptyline Oral Capsule/Disease MGT | Worst Pain | baseline | 6.3 units on a scale | Standard Deviation 2.4 |
| Nortriptyline Oral Capsule/Disease MGT | Worst Pain | post-treatment | 3.2 units on a scale | Standard Deviation 2.1 |
| Nortriptyline Oral Capsule/Disease MGT | Worst Pain | 3 months | 3.4 units on a scale | Standard Deviation 2.7 |
| Benztropine Oral Product/Disease MGT | Worst Pain | 3 months | 4.1 units on a scale | Standard Deviation 2.9 |
| Benztropine Oral Product/Disease MGT | Worst Pain | post-treatment | 4.4 units on a scale | Standard Deviation 2.6 |
| Benztropine Oral Product/Disease MGT | Worst Pain | baseline | 7.2 units on a scale | Standard Deviation 1.9 |
| Benztropine Oral Product/Disease MGT | Worst Pain | 6 months | 3.4 units on a scale | Standard Deviation 2.9 |