Prospective, Cross Over Gabapentin vs Amitriptyline Study on Patients Suffering From Masticatory Muscle Pain

Myofacial Pain Clinical Trial

Official title:

Prospective, Cross Over Gabapentin vs Amitriptyline Study on Patients Suffering From Masticatory Muscle Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02339662
• Other study ID #: gbvsam001-HMO-CTIL
• Status: Recruiting
• Phase: Phase 4
• First received: December 14, 2014
• Last updated: October 18, 2015
• Start date: February 2015
• Est. completion date: January 2017

Study information

• Verified date: October 2015
• Source: Hadassah Medical Organization
• Contact: Doron J Aframian, DMD, PhD
• Phone: 972-2-677-6140
• Email: Dorona[@]hadassah.org.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is comparing two drugs efficacy for the treatment of pain originates from masticatory muscles. The two drugs are - Amitriptlyne (amitriptyline) and Gabapentin (gabapentin), both of them are common use in for the treatment of chronic pain Methods - patient that is diagnosed as suffering from myofacial pain, will receive one of the medications above (Gabapentin or amitriptyline) for one month only, after which he will be invited to pain clinic for control. Two weeks after that, the patient will start taking the other drug for 1 month and then invited again to the department for recall and continue standard treatment . The patient can choose whether to continue medication with one of the drugs or stop this medication treatment. Total duration of the experiment is two and a half months.

Description:

Temporomandibular disorder is one of the main reasons for the pain and damage to the function in the head, jaws and neck (1,2) term is somewhat misleading because it includes two types of pain, one originates from the temporomandibular joint , and another originates mainly from the muscles of mastication - Myofacial pain (MFP). The last is the one we seek to explore the etiology of this pain is explained using a biological-psychological model, which reflects the complex interaction between physical factors, behavioral, social and emotional influences (3). The pain may last from weeks to many months; it is usually more severe on one side of the face, especially at pre-auricular area (front ear). Intensity of the pain is usually moderate; it has a squeezing, dull nature. It worsens during mouth opening and often causes opening restriction (5, 4). One can find trigger points where the pain is harsh and radiates to remote areas. Treatment is often integrated, multi-systemic and comprehensive (7, 6): physical therapy, behavioral therapy, night splints, Trigger point injection, and the use of drugs from different families are used to manage and treat MVP. Among the drugs that we use routinely are: Amitriptyline and nortriptyline from the family of tricyclic antidepressants (TAC's). These drugs were originally intended to treat depression and now days there primary use is to treat chronic pain from muscle origin, the use is in low doses of 10-35 mg /d, with no connection to the anti-depressive effect (8,9,10,11). . Gabapentin is gaba-amino buyic acid (GABA) analogue originally developed as an anti-epileptic (12). This drug is also used as a first treatment in neuropathic pain (13). A study published in 2007 by Kimos et al (14) suggested that using gabapentin at higher doses up to 4200 mg per day is a therapeutic option for myofacial pain. The authors prospectively examined the use of gabapentin versus placebo in myofacial pain over 12 weeks in 50 patients, of whom 36 completed the study, the results demonstrated improvement in any parameter. Another study conducted in our department and accepted for publication in journal of orafacail pain & headache examined retrospectively gabapentin Vs amitriptyline with better results for gabapentin in more complex and widely spread disorder. To gabapentin side effect drug interactions profile better than amitriptyline (16). Moreover, gabapentin has no anticholinergic which usually limits the use of amitriptyline. Therefore, gabapentin may be an attractive alternative for the treatment of MFP. Our clinic use gabapentin routinely as second option after lack of response to amitriptyline. The aim of this study is to compare prospectively the efficacy amitriptyline in low doses up to 20 mg to gabapentin at low doses up to 900mg.

Patients over the age of 18 that will come to orofacial pain clinic in the department of Oral medicine, and which will be diagnosed as suffering from facial pain originating from chewing muscles (MVP) for at least three months, will be invited to participate in the study. The examination is the one we use routinely and includes: patient demographics: age, sex, marital status, occupation, and medical history. Pain characteristics includes : Location, duration, intensity (subjective), the nature of the pain, whether pain is prolonged or not, frequency and duration of attacks, disruption of sleep, quality of life and everyday functioning (work, company), whether the pain is accompanied by autonomic of systemic signs and whether the patient suffers from pain in the body outside the region head and neck. Patient will receive a questionnaire examining the accompanying emotional distress (AXIS II). Masticatory muscle involvement will be examined by palpation, load testing, restriction or non-limitation of mouth opening. All of which are routinely use in our department.

Patients will receive an explanation of the nature of the disease and possible treatments. Patients that would like to participate in the study, will sign a consent form, receive a pain questionnaire and start medication treatment which is acceptable in cases of myofacial pain. The drugs that will be used are: amitriptyline up to 20 mg and Gabapentin up to 900 mg. Patients with any side effects will call to receive instructions. After one month, patients will be invited to our clinic. A clinical examination, similar to one mention above will be performed with re-filling of the questionnaires. First medication treatment will discontinue and after two weeks will be replaced with the equivalent drug. Meaning patients that will begin with amitriptyline will continue with gabapentin (after two weeks break) and vice versa (cross over design). After another month patients will be invited to the clinic for further similar clinical examination and questionnaires fulfilling, then, if necessary patients will continue their preferred treatment. . All patients will give their consent to participate in the study.

Criteria for improvement include: 1. Intensity of pain according to VAS scale. 2. The frequency of the attacks. 3. The frequency of use of other drugs (for the treatment of chronic or acute pain). 4. Improving function - open mouth, free jaw movement. 5. Quality Health Index (AXIS II).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients who suffer from chronic pain more than 3 months prior to arrival

• patients who are capable to reach all the visits in the clinic

• Not pregnant women

Exclusion Criteria:

• Patients with other types of non-muscle origin pain

• Patients without a clear diagnosis.

• Patients who are not originally designated to medication treatment (regardless experiment) for various reasons eg pregnancy.

• Patients who are not interested in medication.

• Patients who are not interested or unable to cooperate.

• Patients who suffer from chronic pain less than 3 months prior to arrival

• Pregnant women

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myofacial Pain

Intervention

Drug:
• Gabapentin
muscles pain treatment
• Amitriptyline
muscles pain treatment

Locations

Country	Name	City	State
Israel	Hadassah MO	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Doron Aframian

Country where clinical trial is conducted

Israel, 

References & Publications (13)

Benoliel R, Eliav E, Sharav Y. Classification of chronic orofacial pain: applicability of chronic headache criteria. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Dec;110(6):729-37. doi: 10.1016/j.tripleo.2010.07.009. — View Citation

Benoliel R, Svensson P, Heir GM, Sirois D, Zakrzewska J, Oke-Nwosu J, Torres SR, Greenberg MS, Klasser GD, Katz J, Eliav E. Persistent orofacial muscle pain. Oral Dis. 2011 Apr;17 Suppl 1:23-41. doi: 10.1111/j.1601-0825.2011.01790.x. Review. — View Citation

Chandra K, Shafiq N, Pandhi P, Gupta S, Malhotra S. Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial--the GONIP Trial. Int J Clin Pharmacol Ther. 2006 Aug;44(8):358-63. — View Citation

Diamond S, Baltes BJ. Chronic tension headache--treated with amitriptyline--a double-blind study. Headache. 1971 Oct;11(3):110-6. — View Citation

Haviv Y, Zadik Y, Sharav Y, Benoliel R. Painful traumatic trigeminal neuropathy: an open study on the pharmacotherapeutic response to stepped treatment. J Oral Facial Pain Headache. 2014 Winter;28(1):52-60. doi: 10.11607/jop.1154. — View Citation

Johannessen SI, Ben-Menachem E. Management of focal-onset seizures: an update on drug treatment. Drugs. 2006;66(13):1701-25. Review. — View Citation

Kimos P, Biggs C, Mah J, Heo G, Rashiq S, Thie NM, Major PW. Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial. Pain. 2007 Jan;127(1-2):151-60. Epub 2006 Oct 9. — View Citation

Kino K, Sugisaki M, Haketa T, Amemori Y, Ishikawa T, Shibuya T, Sato F, Amagasa T, Shibuya T, Tanabe H, Yoda T, Sakamoto I, Omura K, Miyaoka H. The comparison between pains, difficulties in function, and associating factors of patients in subtypes of temporomandibular disorders. J Oral Rehabil. 2005 May;32(5):315-25. — View Citation

Maixner W, Diatchenko L, Dubner R, Fillingim RB, Greenspan JD, Knott C, Ohrbach R, Weir B, Slade GD. Orofacial pain prospective evaluation and risk assessment study--the OPPERA study. J Pain. 2011 Nov;12(11 Suppl):T4-11.e1-2. doi: 10.1016/j.jpain.2011.08.002. — View Citation

Pilowsky I, Hallett EC, Bassett DL, Thomas PG, Penhall RK. A controlled study of amitriptyline in the treatment of chronic pain. Pain. 1982 Oct;14(2):169-79. — View Citation

Plesh O, Curtis D, Levine J, McCall WD Jr. Amitriptyline treatment of chronic pain in patients with temporomandibular disorders. J Oral Rehabil. 2000 Oct;27(10):834-41. — View Citation

Sherman JJ, Turk DC. Nonpharmacologic approaches to the management of myofascial temporomandibular disorders. Curr Pain Headache Rep. 2001 Oct;5(5):421-31. Review. — View Citation

Tjakkes GH, Reinders JJ, Tenvergert EM, Stegenga B. TMD pain: the effect on health related quality of life and the influence of pain duration. Health Qual Life Outcomes. 2010 May 2;8:46. doi: 10.1186/1477-7525-8-46. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pain decrease	pain scale measuring	6 weeks	No
Secondary	The frequency of use of other drugs	breacking drugs registration	6 weeks	No
Secondary	Improving function - open mouth, free jaw movement	opening mouth measurement	6 weeks	No