Managing chronic myalgia temporomandibular disorder (M-TMD): a pragmatic phase III definitive three-arm parallel-group, co-primary outcome, individually randomised open-label controlled superiority trial comparing the clinical and cost-effectiveness and safety of Botulinum toxin type A, Lidocaine, and Amitriptyline/Gabapentin, with internal pilot and cost-effectiveness analysis (MiTiGate)
Myalgia temporomandibular disorder (M TMD)
Participants will be randomized and allocated to one of three arms: 1. Treatment as Usual (TAU): oral amitriptyline or oral gabapentin for 36 weeks 2. Lidocaine injections: three sets of injections, each 12 weeks apart 3. Botox injections: three sets of injections, each 12 weeks apart Amitriptyline and gabapentin dosing titration and regimen are determined by clinician’s usual practice but should lie within or below/slower than NICE’s stated parameters (NICE, 2021): 1. Starting doses: 10 mg amitriptyline once daily in the evening; either 100mg or 300mg of gabapentin once daily, then twice daily on day 2, and then three times daily on day 3. 2. Titration interval: the quickest allowed for gabapentin and amitriptyline is 1 week and the slowest is 4 weeks. 3. Titration increments: 10 mg increments of amitriptyline. 100-300 mg increments for gabapentin which could be applied to all the three times daily regimen or one- or two of the three-times daily intakes. 4. Ceiling doses: 75 mg amitriptyline, 3600 mg gabapentin 5. Duration of therapy: trial amitriptyline or gabapentin for at least 8-12 weeks with a minimum of 2 weeks at the most effective or tolerable dose 6. Issues of tolerability will be discussed with the patient and recorded in the CRF with a possible step back to the previous dose to see if a longer duration at this dose is either more effective or allows upward titration due to the accommodation of any adverse effects. 7. Discontinuation: unless an emergency the quickest allowed discontinuation would be spread over 4 weeks or slower for amitriptyline and gabapentin in similar increments or smaller than upwards titration dose steps. Much slower tapering off over a number of months of either drug is permissible and often required/desirable. 100 units of Botox should be reconstituted with 2 ml of 0.9% normal saline once the participant attends and confirms is going ahead with treatment. Dosages per injection site are then: 1. Masseter 10 units (0.2 ml) per i
1. Adults ≥18 years old 2. Willing and able to give informed consent before trial procedures occurring 3. DC/TMD derived diagnosis of M-TMD with pain for ≥3 months identified as the primary complaint of familiar pain 4. Self-management trialled for ≥6 weeks and not controlled the pain to the patient’s satisfaction 5. Minimum pain intensity of 30 on CPI over the last 3 months 6. For people of childbearing potential: an agreement to use at least an acceptable effective method of contraception or to practise sexual abstinence to avoid pregnancy for the duration of trial involvement.
A documented diagnosis or the patient reports any, of the following: 1. Current use of any of the trial interventions or has used any within the last 12 weeks*. Patients can continue any other treatment modality they currently find helpful for their TMD subject to no absolute contraindications to its use alongside the interventions under investigation. 2. Any other subtype of TMD that is the primary cause of familiar pain detected on clinical examination; familiar pain is pain provoked by clinical exam or testing/movement of a structure that matches the patient’s primary complaint e.g., for M-TMD familiar pain is provoked from examination or use of the muscles of mastication. Patients can have other forms of (painful) TMD comorbid with M-TMD, but these should not be the primary cause of familiar pain determined by DC/TMD-derived diagnostic procedures. 3. Enrolled in another interventional research trial which could affect the outcome of this trial. 4. People who are pregnant, planning pregnancy, or breastfeeding during the time of the study participation*. 5. Current or planned acupuncture within the trial period or 3 months before the trial period*. 6. Lactose intolerance or lactose allergy 7. Fibromyalgia 8. Neuropathic pain 9. Coagulopathy 10. Uncontrolled hyperthyroidism 11. Renal failure 12. Severe liver disease 13. Connective tissue disorders e.g. Ehlers-Danlos syndrome, Epidermolysis bullosa, Marfan syndrome, Osteogenesis imperfecta, Rheumatoid arthritis, Poly/dermatomyositis, Scleroderma, Sjogren’s syndrome, Systemic lupus erythematosus, Vasculitis 14. Any (previous) substance use disorder 15. Concerns from the research or clinical team over patient safety due to psychosocial distress, previous or current mental health illness* 16. Taking any of the following groups of medications: 16.1. Aminoglycoside antibiotics 16.2. Anticholinesterases 16.3. Non-depolarising and depolarising muscle relaxants 16.4. Opiates 16.5. Monoamine oxidase inhibitors (MAOIs) 17. A