The Effectiveness of Adding Pharmacologic Treatment with Clonazepam or Cyclobenzaprine to Patient Education and Self-Care for the Treatment of Jaw Pain upon Awakening: A Randomized Clinical Trial

Aims: To compare the relative effectiveness of a benzodiazepine (clonazepam), a muscle relaxant (cyclobenzaprine), and a placebo for the treatment of jaw pain upon awakening, when each is combined with the recommended nonpharmacological components of initial medical management. Methods: Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All subjects were given education about TMD and a self-care program. Subjects were randomized into 1 of 3 groups: clonazepam (0.5 mg/night), cyclobenzaprine (10 mg/night), or placebo. The primary outcome measure was the subjects’ average intensity of jaw pain upon awakening over the prior week. This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial. A secondary outcome measure was sleep quality based on the Pittsburgh Sleep Quality Index. Results: Within-group changes showed a statistically significant (P < .001) decrease in jaw pain upon awakening for all 3 groups. Betweengroup differences demonstrated a statistically significant difference (P < .016) between cyclobenzaprine and placebo, and between cyclobenzaprine and clonazepam. There was no significant effect on sleep quality in any group. Conclusion: This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening. Based on the subjects’ report of sleep quality, these medications failed to significantly improve sleep in the short term.

temporomandibular joint; myofascial pain; clonazepam; cyclobenzaprine; randomized clinical trial (RCT)

1. National Institute of Health. Management of Temporomandibular Disorders. National Institute of Health Technology Assessment Conference statement. J Am Dent Assoc 1996;127:1595–1606.

2. Simons DG, Travell JG. Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore: Williams & Wilkins Co., 1998.

3. Carlson CR, Reid KI, Curran SL, Studts J, Okeson JP, Falace D, et al. Psychological and physiological parameters of masticatory muscle pain. Pain 1998;76:297– 307.

4. Drangsholt M, LeResche L. Temporomandibular Disorder Pain. In: Crombie IK (ed). Epidemiology of Pain: A Report of the Task Force on Epidemiology of the International Association for the Study of Pain. Seattle: IASP, 1999:203–233.

5. Schiffman EL, Fricton JR, Haley DP, Shapiro BL. The prevalence and treatment needs of subjects with temporomandibular disorders. J Am Dent Assoc 1990;120:295–303.

6. Fricton JR, Kroening R, Haley D, Siegert R. Myofascial pain syndrome of the head and neck: A review of clinical characteristics of 164 patients. Oral Surg Oral Med Oral Pathol 1985;60:615–623.

7. Rudolph U, Crestani F, Benke D, et al. Benzodiazepine actions mediated by specific gamma-aminobutyric acidA receptor subtypes. Nature 1999; 401:796–800.

8. Katz WA, Dube J. Cyclobenzaprine in the treatment of acute muscle spasm: Review of a decade of clinical experience. Clin Ther 1988;10:216–228.

9. Spiller HA, Winter ML, Mann KV, Borys DJ, Muir S, Krenzelok EP. Five-year multicenter retrospective review of cyclobenzaprine toxicity. J Emerg Med 1995;13:781–785.

10. Kobayyashi H, Hasegawa Y. Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems. Eur J Pharm Biopharm 1996;311:29–35.

11. Carette S, Bell MJ, Reynolds WJ, Haraoui B, et al. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia: A randomized double-blind clinical trial. Arthritis Rheum 1994;37: 32–40.

12. Santandrea S, Monotone F, Sarzi-Puttini P, Boccassini L, Caruso I. A double-blind crossover study of two cyclobenzaprine regimens in primary fibromyalgia syndrome. J Int Med Res 1993;21:74–80.

13. Lance JW, Anthony M. Cyclobenzaprine in the treatment of chronic tension headache. Med J Aust 1972;2: 1409–1411.

14. Basmajian JV. Cyclobenzaprine hydrochloride effect on skeletal muscle spasm in the lumbar region and neck: Two double-blind controlled clinical and laboratory studies. Arch Phys Med Rehabil 1978;59:58–63.

15. Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders: Review, criteria, examination and specifications, critique. J Craniomandib Disord 1992;6:301–355.

16. Wright EF, Schiffman EL. Treatment alternatives for patients with masticatory myofascial pain. J Am Dent Assoc 1995;126:1030–1039.

17. Fricton JR. Musculoskeltal measures of orofacial pain. Anesth Prog 1990;37:136–143.

18. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, and Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.

19. Fricton JR. Clinical trials for chronic orofacial pain. In: Bonica JJ, Albe-Fessard DG (eds). Advances in Pain Research and Therapy, Vol 18. New York: Raven, 1991:708–712.

20. Ellenbaas JK. Centrally acting oral skeletal muscle relaxants. Am J Hosp Pharm 1980;37:1313–1323.

21. Bercel NA. Cyclobenzaprine in the treatment of skeletal muscle spasm in osteoarthritis of the cervical and lumbar spine. Curr Ther Res Clin Exp 1977;4:462–468.

22. Singer EJ, Sharav Y, Dubner R, Dionne RA. The efficacy of diazepam and ibuprofen in the treatment of chronic myofascial orofacial pain. Pain 1987;(suppl 4): S83.

23. Singer EJ, Dionne RA. A controlled evaluation of ibuprofen and diazepam for chronic orofacial muscle pain. J Orofac Pain 1997;11:39–146.

24. DeNucci DJ, Dionne RA, Dubner R. Identifying a neurobiologic basis for drug therapy in TMDs. J Am Dent Assoc 1996;27:581–593.

25. Harkins S, Linford J, Cohen J, Kramer T, Cueva L. Administration of clonazepam in the treatment of TMD and associated myofascial pain: A double-blind pilot study. J Craniomandib Disord 1991;5:179–186.

26. Dionne RA. Pharmacologic treatments for temporomandibular disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:134–142.

27. Dellernijn PL, Fields HL. Do benzodiazepines have a role in chronic pain management? Pain 1994;57(2):137– 152.

28. Wright E, Anderson GC, Schulte J. A randomized clinical trial of intraoral soft splints and palliative treatment for masticatory muscle pain. J Orofac Pain 1995;9:192–199.

29. Laskin DM, Green CS. Influence of the doctor patient relationship on placebo therapy for patients with myofascial pain dysfunction (MPD) syndrome. J Am Dent Assoc 1972;85:892–894.

30. Agargun MY, Tekeoglu I, Gunes A, Adak B, Kara H, Ercan M. Sleep quality and pain thresholds in patients with fibromyalgia. Comp Psychiatry 1999;40:226–228.