Nortriptyline Versus Pregabalin in Atypical Odontalgia: A Comparative Study of Efficacy and Safety

INTRODUCTION

Atypical odontalgia (AO) is a rare chronic pain condition in the area of teeth, jaws and face¹. AO is also known as phantom tooth pain. As etiology of this is unknown so other name of this is persistent idiopathic facial pain². Some reports suggest the association with several psychological and neuropathic conditions^3-4. AO is difficult to distinguish from toothache of dental origin. AO has been described as tooth-related pain or pain located at a site where a tooth was extracted or following some type of surgical therapy, in absence of clinical or radiographic evidence of tooth, soft and hard tissue pathology explaining the pain5. Pain has been ongoing for at least 6 months, is not paroxysmal in character, and is continuous or present during most of the day. Sleep is usually unaffected. All adult ages and both sexes can be affected, but with a preponderance of women 45–60 years⁵. Diagnosis of AO has been made with history taking and somatosensory changes such as hyperesthesia, allodynia and exacerbation of pain with temperature. Patients with AO are treated unnecessarily with root canal (endodontic) therapy or extraction of otherwise healthy teeth, after which symptoms persist6. The diagnosis of AO was made according to The In­ternational Classification of Headache Disorders criteria7 i.e. continuous pain in the teeth or in a tooth socket after extrac­tion in the absence of any identifiable dental cause.

DIAGNOSTIC CRITERIA

A. Pain in the face, present daily and persisting for all or most of the day, fulfilling criteria B and C

B. Pain is confined at onset to a limited area on one side of the face, and is deep and poorly localized

C. Pain is not associated with sensory loss or other physical signs

D. Investigations including X-ray of face and jaws do not demonstrate any relevant abnormality.

There is a strong association with a history of anxiety/depression in patients with AO. Neuropathic pain is generally managed8-10 with a tricyclic antidepressant (TCA) or with certain antiepileptic drugs. In tricyclic antidepressant^11-12 group, Nortriptyline may be better tolerated than amitriptyline. Pregabalin^13-14 in doses of 150-600 mg/day has been shown to be effective in neuropathic pain e.g. diabetic peripheral neuropathy, post-herpetic neuralgia, post-traumatic neuropathy.

This study has been conducted to compare the therapeutic efficacy and tolerability of nortriptyline and pregabalin in patients suffering from AO.

MATERIAL & METHODS

Selection of patients

The study was conducted at a tertiary care dental college in Kanpur from May 2008| to June 2012. After approval of institute’s ethics committee, an informed consent was discussed, approved and signed by all volunteers. All these participants were between 18 to 82 years of age with mean age of 47 years. Inclusion criteria were chronic pain of at least 6 months duration in the region of teeth or jaw with no pathological cause detectable during clinical or radiological examinations. Exclusion criteria were patient with trigeminal neuralgia, migraine, sinusitis, apical periodontitis or marked renal function impairment. These cases were intensively scrutinized. A total of 48 such cases (15 male and 33 female) were included for the present study. Participants thus selected were randomly assigned to take either Nortriptyline (start with 10-25 mg at bedtime then titrate upto antidepressant drug level, max. daily dose 75 mg) or a Pregabalin (start at 75 mg twice daily maximum dose 300 mg twice daily). Patients visited the clinic for assessment at baseline, week 1 and week 6 (or upon early discontinuation). Patients were asked for symptoms and were helped to grade the pain frequency, duration and particularly the intensity using the numeric rating scale (NRS), visual analogue scale (VAS) or face rating scales characteristics (Table I, Fig. I). The presence of depression or a sleep disorder was also evaluated. At each visits, evaluations were made for each patients by the same investigator.

Faces rating scale (FRS):

Participants who had difficulty using the numbers on the visual/numerical rating scale were assisted with the use of the six facial expressions suggesting various pain intensities. They were asked to choose the face that best described how they felt.

Fig :I

Here the far left face indicates ‘No hurt’ and the far right face indicates ‘Hurts worst’. Number corresponding to the face chosen was documented.

Safety and tolerability were assessed on the basis of the adverse events reported or by comparing the baseline symptoms with post-drug symptoms, or changes in vital signs and physical examination findings recorded before and at the end of treatment.

Stat analysis

The data thus obtained was evaluated by using the statistical Package for Social Science SPSS v. 16). A Wilcoxon Signed ranks test was used to analyze the percentage change.

RESULT

Out of 48 cases only 36 participants completed the study; 21 (6 male and 15 female) in Nortriptyline group and 15 (5 male and 10 female) in pregabalin group. After a week of therapy these participants were again evaluated on the basis of visual analog scale. All these participants were counseled to continue their "medication" for another 5 weeks.

After a total of 6 weeks of therapy, study results were compared. Nortriptyline treated patients responded much better than the pregabalin group. 16 patients became absolutely pain free (76.19%), 3 patients were almost pain free (14.29%), 2 patients however did not had any benefit (9.53%). Compared to this, in pregabalin group none became absolutely pain free (0 %), 3 reported that they are much better (20%), 5 (33.3%) had some relief while 7 patients (46.67%) had no improvement or complained of worsening symptoms (Table II).

We did not encounter any major problem in Nortriptyline or pregabalin group. Both the drugs were well tolerated. In the nortriptyline group, out of four patients who experienced adverse effects, two complained of dry mouth and epigastric distress, one had sweating and tremors, and one patient showed a postural hypotension. In the pregabalin group, two patients complained of headache, one patient had nausea, and in two patients there was a peripheral edema. According to the CTC grading of adverse drug reactions, all the reported side effects were of grade 1 (mild).

DISCUSSION

Atypical odontalgia is a chronic, idiopathic pain condition of face. Diagnosis is difficult because this condition is a diagnosis of exclusion¹⁵. Management of the patient is better achieved through a multidisciplinary approach intended to improve patient’s quality of life as well as relieving the pain. This involves reducing the disability caused by the pain often with an increase in mood, activity and social contact. Medical management of idiopathic facial pain is mainly through the use of tricyclic antidepressant and anticonvulsant drugs. Anticonvulsant drugs, including pregabalin, increase the risk of suicidal thoughts or behaviours in people using them¹⁶. Monitor people treated with pregabalin for any unusual changes in mood or behaviour. There is a strong association with a history of anxiety/depression in patients with AO and our result also suggest that Nortriptyline, a tricyclic antidepressant is better than pregabalin in this condition. Depression may be a cause or outcome but shows a dramatic response to antidepressants.

CONCLUSION

In AO, Nortriptyline scores much better than pregabalin. Nortriptyline was found to be virtually safe, more efficacious and cost effective than Pregabalin. Disorders of this type require psychological support to accompany drug treatment. The findings of this exploratory study can be confirmed by multicentric, randomized, double-blind large population studies.

REFERENCES