|Year : 2021 | Volume
| Issue : 2 | Page : 171-176
Comparative evaluation of the efficacy of gabapentin and gabapentin in combination with nortriptyline in the management of pain-related temporomandibular disorders
Mohsin Muzaffar Tak, Altaf Hussain Chalkoo, Tariq Ahmad Bhat, Tauseefa Jan
Department of Oral Medicine and Radiology, Government Dental College, Srinagar, Jammu and Kashmir, India
|Date of Submission||08-Oct-2020|
|Date of Decision||15-May-2021|
|Date of Acceptance||17-May-2021|
|Date of Web Publication||23-Jun-2021|
Dr. Tariq Ahmad Bhat
Department of Oral Medicine and Radiology, Government Dental College and Hospital, Srinagar, Jammu and Kashmir - 190 010
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Temporomandibular disorders (TMDs) are considered the most common orofacial pain conditions of nonodontogenic origin. The current perspective regarding TMD is multidimensional. If the pain becomes chronic, it can have a great impact on the social and emotional behavior of the patient. Materials and Methods: A total of 40 patients between the age groups of 18 and 45 years were included in the study. These patients were divided into two groups comprising 20 patients each. Group I was prescribed gabapentin and was advised to take the medicine twice daily. Group II was prescribed gabapentin along with nortryptyline twice daily. Patients in each group were evaluated at the end of every week using a visual analog scale (VAS) score for pain, maximum interincisal mouth opening, and several muscle tenderness sites for 3 weeks, and a comparison was made. Results: The age range in group I was 19–45 years, whereas in group II it was 18–45 years with a P value of 0.711. Female predominance was observed in both groups as 65% of patients were females in group I and 60% were females in group II and P value obtained was 0.74. VAS score decreased more rapidly in group II than group I. The P value obtained was <0.001 at the end of the third week. Comfortable moth opening shows a more effective increase in group II than group I. The P value (0.003) shows significance at the end of the third week. The mean number of muscle tenderness sites at the end of 3 weeks in group I and group II reduced to 1.15 and 0.40, respectively. Conclusion: The combination therapy of gabapentin with nortryptyline was found to be more effective than gabapentin alone.
Keywords: Central sensitization, gabapentin, nortryptyline, orofacial pain, temporomandibular disorders
|How to cite this article:|
Tak MM, Chalkoo AH, Bhat TA, Jan T. Comparative evaluation of the efficacy of gabapentin and gabapentin in combination with nortriptyline in the management of pain-related temporomandibular disorders. J Indian Acad Oral Med Radiol 2021;33:171-6
|How to cite this URL:|
Tak MM, Chalkoo AH, Bhat TA, Jan T. Comparative evaluation of the efficacy of gabapentin and gabapentin in combination with nortriptyline in the management of pain-related temporomandibular disorders. J Indian Acad Oral Med Radiol [serial online] 2021 [cited 2021 Jul 29];33:171-6. Available from: https://www.jiaomr.in/text.asp?2021/33/2/171/319064
| Introduction|| |
Orofacial pain disorders are extremely common and debilitating. They usually affect the head, face, and neck region. Each dental specialty developed its understanding, values, and philosophies about temporomandibular disorders (TMDs), which have been passed down and accepted through the generations. The year 1934 can be considered as the beginning of the history of TMDs. Dentists were encouraged to focus their attention on occlusal and jaw relationships as the primary cause of TMDs. Changing the occlusal and skeletal relationships to a supposed optimal level was at the heart of many treatment principles and philosophies. The field of TMD has been profoundly influenced by research findings in neurophysiology and pathophysiology of pain, anatomy, endocrinology, behavioral sciences, and psychology over the last 20 years. The paradigm change continues with a flood of new information about the mechanism of pain, as well as significant developments in pain neurophysiology and neuropharmacology. Clark published an excellent analysis of numerous hypotheses that could explain the effectiveness of occlusal appliances, suggesting that cognitive knowledge might be as important as, if not more important, than, structural changes that are reportedly developed in the efficacy of appliance therapy. Both tissue and nerve damage can cause long-term changes in the central nervous system (CNS), known as CNS plasticity, which causes pain to last long after the initial injury has healed. Various studies have discovered correlations between chronic pain activity and chronic TMD pain and other pain disorders, emphasizing the importance of chronic pain management from both the CNS plasticity and psychosocial and behavioral perspectives. The modern biopsychosocial approach to TMD management focuses on the integration of biological, psychosocial, and social factors that contribute to the onset, maintenance, and remission of TMD.
Aim of the study
To compare the effectiveness of gabapentin alone and in combination with TCA (tricyclic antidepressants) in reducing pain intensity, increasing maximum mouth opening, and decrease in the number of muscle tenderness sites reported by subjects with TMD after 3 weeks.
| Materials and Methods|| |
The study was carried out in the Department of Oral Medicine and Radiology, Dental College and Hospital, Srinagar. The study was approved by the Institutional Review Board (IRB), vide letter no. Prostho/GDC/5088 and followed all the recommendations of the Helsinki Declaration. Written informed consent was received from all individual patients included in the study. Patients were informed that their participation is voluntary and they are free to withdraw at any time. Patients were also informed that the results obtained from this study can be used for academic activities (publications) or patient care. This study was conducted over 1 year. It was an in vivo prospective study conducted in a tertiary care center.
For each participant, a standardized protocol was followed that contained collection of personal and demographic data followed by a detailed recording of clinical case history at the time of diagnosis regarding onset, duration, and progress of symptoms. Pain characteristics such as type, nature, and severity were noted. The pain was evaluated from responses to the visual analog scale (VAS), 100 mm continuum. This is followed by a complete examination of muscles, temporomandibular joint (TMJ), and dental structures for evaluating signs and symptoms of TMD. All the muscles of mastication were palpated for tenderness, and positive findings were noted down. In TMJ examination, facial symmetry/asymmetry, the extent of mouth opening, interincisal distance (IID), and mandibular gait for any deviation or deflection were observed by asking the participant to open and close his/her mouth three times. The TMJ was palpated with gentle digital pressure bilaterally to assess the degree of pain and quality of joint noises (clicking/crepitus, and their relationship with jaw opening. Auscultation with a stethoscope was done for confirmation of palpatory findings. A complete dental examination was performed which includes a recording of maxilla–mandibular relationship, occlusal interferences (presence of any high points or premature contacts), presence of any restoration or prosthesis, and missing teeth special emphasis was given to the attrition and occlusal wear facet which would suggest the presence of parafunctional habits such as bruxism or clenching. when data recording for each participant had been completed, extrapolation was carried according to RDC/TMD axis I and II criteria, by routine clinical practice. All the participants were classified into diagnostic categories according to RDC/TMD criteria. Most of the patients in our study were suffering from local myalgia, myofascial pain, myofascial pain with referral, internal derangements, and masticatory muscle pain secondary to cervical pain.
Participants with pain-related TMDs who reported to the Department of Oral Medicine and Radiology were divided into two study groups, a group I and group II. This clinical study involves the comparison of the early effectiveness of gabapentin and gabapentin in combination with nortryptyline for pain-related TMDs.
Sample size determination
Using G-POWER software (version 3.0.10), it was estimated that the least number of patients required in each group with an effect size of 0.46, 80% power, and 5% significance level is 20. As comparison between 2 groups was undertaken, a sample of 40 patients was included in our study.
This study consisted of 40 participants who reported to the Department of Oral Medicine and Radiology. These participants were divided into two groups randomly according to the following inclusion and exclusion criteria
The following inclusion criteria were used:
- The age range of participants selected was 18–45 years old patients.
- Masticatory muscle pain for at least 3 months.
- Chronic masticatory muscle pain not attributable to recent acute trauma or previous infection.
- Chronic pain in the masticatory muscles that are not attributable to an active inflammatory cause.
The following exclusion criteria were also applied.
- Clinical evidence of inflammatory TMD.
- Pregnant or nursing females.
- Epilepsy, cardiac, renal, or hepatic disorders.
- History of intolerance to gabapentin or any of the components of the formulation.
- Dental or periodontal disease, oral pathology lesions, oral infections, or neuropathic facial pain.
- Patients wearing an occlusal splint appliance for less than 6 months were excluded.
Group I was prescribed gabapentin (100 mg) twice daily whereas Group II has prescribed gabapentin (100 mg) along with nortriptyline (10 mg). The age group selected for the study was 18–45 years. In the initial visit, baseline scores were recorded and medication was prescribed. The participants were scheduled every week for 3 weeks and scores were evaluated after every week.
Three outcome measures were evaluated at the initial visit (baseline), at the end of the first week, at the end of the second week, and at the end of the third week.
Pain intensity related to TMD was reported on 100 mm VAS. Participants were asked to report the average pain intensity experienced in the previous week on a VAS. The VAS used was a 100-mm long with both ends labeled with the two extreme boundaries of pain sensation: No pain at one end and worst pain at the other end. Moderate pain was considered to be over 30 mm and severe pain over 54 mm.
Comfortable mouth opening
Maximum IID was measured with a vernier caliper. The measurement most often used to assess mouth opening is the summation of IID attained during active opening by the subject and the overbite of the subject.
The number of tender sites in the masticatory apparatus was examined for sensitivity to palpation. The following muscles were examined bilaterally: Masseter, temporalis, medial pterygoid, lateral pterygoid. The patient's response was recorded to be positive if it was reported below the normal threshold value for the palpated site. A response was considered negative when reported to be equal to or higher than the normal threshold value of the palpated site.
The recorded data was compiled and entered in a spreadsheet (Microsoft Excel) and then exported to the data editor of Statistical Package for the Social Sciences (SPSS) software program, version 20.0 (SPSS, Chicago, Illinois). Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables were summarized as frequencies and percentages. The student's independent t- test was used for comparing continuous variables. Chi-square test or Fisher's exact test, whichever appropriate, was applied for comparing categorical variables. A value of P < 0.05 was considered statistically significant. All P values were two- tailed.
| Results|| |
As shown in [Table 1], the mean age of patients in group I was 32.3 years with an SD of 7.28 years when compared to the mean age of patients in group 2 which is 31.2 years with an SD of 3.86. The age range in group I was 19–45 years, whereas in group II it is 18–45 years. The P value of 0.711 was obtained as shown in [Table 1].
Female predominance was observed in both the groups as 65% of patients were females in group I and 60% were females in group II as depicted in [Table 2]. The P value obtained was 0.74.
VAS score which was obtained in both the groups at the baseline and the end of each week for 3 weeks showed a progressive decrease in mean VAS scores. The progressive VAS score was deceased more rapidly in group II than in group I as depicted in [Table 3]. The P value obtained was <0.001 at the end of the third week.
|Table 3: Comparison based on VAS score in two groups at various intervals of time|
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The comfortable mouth opening as depicted in [Table 4], shows a progressive increase from the baseline where the mean mouth opening in group I and group II was 33.90 mm and 32.98 respectively. It increased towards the end of the third week where mouth opening is to 38.35 mm in group I and 41.50 mm in group II. Comfortable mouth opening, when compared between the two groups at various intervals of time, shows a more effective increase in group II than group I. The P value (0.003) shows significance at the end of the third week. As such, there is no study on gabapentin evaluating maximum comfortable mouth opening in TMD patients.
|Table 4: Comparison based on maximum interincisal mouth opening in two groups at various intervals of time|
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The mean number of muscle tenderness sites at baseline in group I and group II are 5.50 and 5.40 respectively as shown in [Table 5]. there was a decrease in the mean number of muscle tenderness sites in both groups but greater in group II in comparison to the group I. The mean number of muscle tenderness sites at the end of 3 weeks in group I and group II reduces to 1.15 and 0.40 respectively. The P value for the mean number of muscle tenderness sites becomes significant at the end of 3 weeks (0.008).
|Table 5: Comparison based on decrease in muscle tenderness sites in two groups at various intervals of time|
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| Discussion|| |
TMDs represent a significant public health problem. The population affected by TMDs constitutes 5-12%. The duration of pain in TMD patients seeking treatment affects the HRQoL (health-related quality of life) and psychological well-being. The quality of life of patients with TMDs was affected by the presence of pain and alterations in mental health with the perception of reduced quality of life. The psychological assessment in these patients leads the clinician to multidimensional, biobehavioral therapies rather than somatically based therapies.
In our study both the groups shows a predominance of female patients. This result is consistent with several studies that also found higher prevalence of TMD in females. Women are 2-4 times more likely to develop TMD during their lifetime than men.
The prevalence of TMD is low in children, increases during adolescence and young adulthood, and appears to peak during midlife. The two OPPERA (Orofacial Pain Prospective Evaluation and Risk Assessment) studies were consistent in finding a positive association between age and TMD incidence. The age range according to two OPPERA studies is 18–44 years., In our study, the age group which reported pain-related TMD disorders was 18–45 years of age which is consistent with the two OPPERA studies.
Gabapentin can be used as an effective option for the treatment of pain-related TMD disorders as central sensitization plays an important role in the development and progression of TMD disorders., Gabapentin is a novel anticonvulsant that works on the CNS and has shown promise in a variety of chronic pain disorders, including TMD. Many studies have shown the effects of gabapentin in a variety of pain conditions, ranging from neuropathic pain to orofacial pain. Gabapentin taken at bedtime, according to a new study, reduces nighttime muscle activity in the same way as stabilization appliance does.
A clinical trial by Kimos et al. revealed gabapentin appears to have a statically significant difference with the control group at week 12 for the VAS-pain whereas for palpation index tactical difference appears at week 8. Our study revealed a reduction in VAS scores and a decrease in muscle tenderness sites which appears to be statically significant after 3 weeks. There is no consensus in the literature regarding the time required by the drug to produce its effect. It can range from weeks to several months when treating intractable pain conditions and varies from patient to patient.
A good pharmacotherapeutic response of persistent myofascial pain has been shown with stepped treatment with nortriptyline and gabapentin. Patients who were nonresponding to nortriptyline showed good response with gabapentin. A stepped approach using TCAs and gabapentin resulted in 54.8% of all treated patients reporting improvements of > 50% in VAS scores. In terms of reduction in VAS scores, our study shows significant results (P < 0.05) after the third week when nortryptyline was used in combination with gabapentin.
Antidepressant drugs have been used for more than three decades for the management of pain arising from TMD. In a study by Plush, it was found that the reduction in pain intensity was observed when using 30 mg of amitriptyline. Moreover, patients who received amitriptyline in combination with cognitive behavioral therapy continued to improve in terms of VAS scores even when the therapy was discontinued. The study conducted by McQuay et al. revealed the use of 25 mg of amitriptyline resulted in a significant reduction of pain intensity after 3 weeks versus the placebo group. The results in this study show a significant reduction in VAS scores after 1 week compared with the baseline (P > 0.05). Significant reductions in VAS scores were seen at the 7th week, compared with the baseline (P < 0.05). If we compare the reduction in VAS scores with our study the significant reduction in VAS scores were seen at the end of third week compared to baseline (P < 0.05). The early effectiveness may be due to the synergistic phenomenon of two medications. In a study of Rizzatti-Barbosa et al. significant reduction in pain intensity was noticed after administering 25 mg of amitriptyline versus the placebo group after 2 weeks of treatment. The results showed a significant difference in the intensity of pain or discomfort from the baseline and in the subsequent weeks experienced in the amitriptyline group compared to the placebo group. In our study, we used gabapentin (100 mg) in combination with nortriptyline (10 mg), the lowest dose used to date for TMD pain with significant results after 3 weeks in terms of decreasing VAS scores, decrease in muscle tenderness sites, and progressive increase in comfortable mouth opening. A study was done by Orbai et al. where 20 out of 26 patients with chronic low backache improved following amitriptyline or nortriptyline treatment and the majority (55%) of them showed improvement at a dose of 10 mg/day.
Both the medicines have got their analgesic effect for chronic pain. When used in combination a synergistic pharmacotherapeutic effect was achieved. We tried a combination of both drugs as a treatment modality in our study for TMD patients. The results obtained in our study are significant in terms of decreasing pain scores, increase in comfortable mouth opening and decrease in muscle tenderness sites. The results were statically significant at the end of the third week. When compared with gabapentin, the combination showed better results in our study.
Limitations and future prospects
The present study has certain limitations that reduce the strength of our conclusions, the biggest limitation being a sample size. However, this study encourages the execution of a full- scale study as our results were favorable. The outcome measures of orofacial pain treatment are very subjective, which warrants the adherence to a strict clinical protocol involving blinding. Execution of those protocols is very cumbersome and the recruitment process is time consuming. For this reason, we feel that the results of our preliminary study are valuable, although the number of patients is small.
Gabapentin is well tolerated with few serious adverse effects as compared to NSAIDs as a treatment modality for pain-related TMDs. Patients in our study show adequate response at a mere dose of 100 mg. Dose titration and frequency of dosage can vary according to the geographical area, age, gender, or race. Different studies can be taken up to study the response of dose titration, frequency of dosage, and administration of medication according to the pattern of onset symptoms in TMDs. Gabapentin seems to have a good scope as a treatment modality in pain-related TMD patients.
| Conclusion|| |
The combination therapy of gabapentin and nortriptyline seems to be more efficacious than gabapentin alone for pain-related TMDs; therefore, we recommend the use of this combination in patients who show partial response to either drug given alone and seek additional pain relief, increase comfortable mouth opening and decrease muscle tenderness in minimum time duration.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]