INTRODUCTION:
According to the International Headache Society, Trigeminal neuralgia is defined as "a
disorder characterized by recurrent unilateral brief electric shock-like pain, abrupt in
onset and termination, limited to the distribution of one or more divisions of the
trigeminal nerve and triggered by innocuous stimuli" [1]. The trigeminal nerve (V) is the
fifth and largest of all cranial nerves, and it is responsible for detecting sensory
stimuli that arise from the craniofacial area including the forehead, cheek, and lower
jaw [2]. It is a highly debilitating disorder that impacts on basic human functions such
as talking, eating, drinking and touching the face, thereby resulting in a poor quality
of life [3, 4].
Trigeminal neuralgia is considered a rare condition, affecting 4 to 13 people per 100,000
people annually. Women are more commonly affected than men. The female-to-male prevalence
ratio ranges from 1.5 to 1.7 to 1. Most cases of trigeminal neuralgia occur after age 50,
but the disease may be seen in the second and third decades of life; trigeminal neuralgia
is rarely diagnosed in childhood. The lifetime prevalence of trigeminal neuralgia in
population-based studies is estimated at 0.16% to 0.3% [5, 6]. A Pakistani study by Usman
J, et al. audited the trigeminal neuralgia patients visiting the tertiary care hospital
over a period of two years and reported a 0.46% prevalence of trigeminal neuralgia [7].
Trigeminal neuralgia is usually suspected through historical, physical and clinical
examination findings. These patients should undergo neuroimaging with magnetic resonance
imaging (MRI) and magnetic resonance angiography (MRA) whenever possible for confirmation
of trigeminal neuralgia [6, 8, 9]. Medical therapy is the preferred initial therapeutic
intervention for patients with trigeminal neuralgia. The antiepileptics carbamazepine or
oxcarbazepine are the preferred initial therapeutic agents [10]. Carbamazepine is FDA
indicated for epilepsy, trigeminal neuralgia, and acute manic and mixed episodes in
bipolar I disorder [11]. Oxcarbazepine is an analogue of carbamazepine and is often used
in acute orofacial pain episodes lasting seconds, as well as in the trigeminal nerve and
its branches. Oxcarbazepine is preferred over carbamazepine because it has advantages
over carbamazepine and lesser negative effects [12]. A study by Iqbal S, et al was
conducted on efficacy of carbamazepine and oxcarbazepine for treating trigeminal
neuralgia and reported a complete response in 42.9% of patients with carbamazepine and
67.9% of patients with oxcarbazepine. Frequency of adverse effects was higher for
carbamazepine as that of Oxcarbazepine. i.e. 35.7% vs. 14.3% [13]. Another study by Di
Stefano G, et al. reported that the initial proportion of responders was 88.3% with
carbamazepine, and 90.9% with oxcarbazepine. Side effects occurred more frequently in
patients treated with carbamazepine (43.6%) than with oxcarbazepine (30.3%) [14].
The rationale of the study is to compare the efficacy of oxcarbazepine and carbamazepine
in the management of trigeminal neuralgia in patients presenting in the outpatient
department of neurology at Jinnah Postgraduate Medical Centre. International and local
data is very scarce regarding the comparisons of both of these drugs for treating
trigeminal neuralgia. However, the effects of these drugs have been documented in the
literature in comparison to other drugs or as a triple therapy combination. So, taking
both drugs as monotherapy for treating trigeminal neuralgia can lead us to conclude which
drug is superior as a monotherapy so that, in the future, drug with better efficacy will
be preferred. The results of the study will be helpful in the selection of an appropriate
and more effective drug for the treatment of trigeminal neuralgia.
OBJECTIVE:
To compare the efficacy of oxcarbazepine and carbamazepine in the management of
trigeminal neuralgia in patients presenting in outpatient department of neurology Jinnah
Postgraduate Medical Centre.
OPERATIONAL DEFINITION:
TRIGEMINAL NEURALGIA:
It will be confirmed by using International Classification of Headache Disorders
edition 3 (ICHD-3) diagnostic criteria.
Diagnostic Criteria:
Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more
divisions of the trigeminal nerve, with no radiation beyond, and fulfilling criteria
B and C.
A. Pain has all of the following characteristics: lasting from a fraction of a
second to 2 minutes, severe intensity and electric shock-like, shooting, stabbing or
sharp in quality.
B. Precipitated by innocuous stimuli within the affected trigeminal distribution.
C. Not better accounted for by another ICHD-3 diagnosis.
VISUAL ANALOGUE SCALE (VAS)
VAS is a tool used to measure pain, with 0 indicating no pain and 10 indicating the
worst pain. Pain intensity on the VAS is divided as follows:
0 for no pain.
1-3 for mild pain.
4-6 for moderate pain.
7-10 for severe pain.
EFFICACY The effectiveness of both drugs will be measured by the frequency of pain
attacks.
Good Response: No attacks of pain.
Average Response: Two to three attacks of pain per day.
Nonresponsive: No decrease in the frequency of attacks of pain.
SAFETY Safety of patient will be assessed on presence of side effects such as
drowsiness (feeling sleepy or tired during the day time), dizziness (feeling faint,
weak or unsteady), diplopia (double vision), nausea (feeling to vomit), and
hyponatremia (serum sodium level < 135 mEq/L).
HYPOTHESIS:
Null Hypothesis: There is no difference in the efficacy of Oxcarbazepine and
carbamazepine in the management of trigeminal neuralgia.
Alternative Hypothesis: Oxcarbazepine is more effective than carbamazepine in the
management of trigeminal neuralgia.
MATERIAL AND METHODS:
SETTING:
This study will be conducted at Ward 28, Department of Neurology Jinnah Postgraduate
Medical Centre (JPMC) Karachi.
DURATION OF STUDY:
Six months
STUDY DESIGN:
Randomized controlled trial.
SAMPLE SIZE:
The sample size calculation was done by using the "Open Epi" software for sample size
calculation by using the proportion of Iqbal S, et al. who reported a complete response
in 42.9% of patients with carbamazepine and 67.9% of patients with oxcarbazepine [13], by
taking confidential interval 95% and power 80%. Calculated sample size was 122 (61 in
each group).
SAMPLING TECHNIQUE:
Non-probability consecutive sampling technique.
DATA COLLECTION PROCEDURE:
This study will be performed after the permission of Research evaluation unit (REU) of
College of Physicians and Surgeons Pakistan (CPSP) and written informed consent for the
study will be obtained from the patient who fulfill the inclusion criteria.
Outpatient visiting Ward 28 of Neurology Department Jinnah Postgraduate Medical Centre,
Karachi and who fulfills the inclusion criteria will be included in the study. Detailed
demographic details of each patient including name, gender, age, residence, educational
status and employment status will be obtained. Each patient will be assessed for duration
of pain, severity of pain, frequency of pain and side of pain. After that each patient
will be assessed for pain severity by using the VAS. Each patient will be asked to point
out the number on VAS that best represents the intensity of their pain.
Patients will be randomly distributed to either Group A (oxcarbazepine) or Group B
(carbamazepine) using a lottery method. Group A patients will be treated with
oxcarbazepine (150 mg twice daily up to 1800 mg) and Group B patients will be treated
with carbamazepine (100 mg twice daily up to 1200 mg). Dose will depends on severity of
symptoms. Patients will be counseled about presence of side effects such as drowsiness,
dizziness, diplopia, nausea and hyponatremia, and instructed to report to principal
investigator in case of side effects causing any disability or interference in daily
activities. Each patient will be followed up every month and the final outcome i.e., the
efficacy of the treatment will be assessed six months after the treatment. All results
will be collected and filled in proforma accordingly by the researcher.
DATA ANALYSIS PROCEDURE:
After collection of data the analyses will be conducted by using Statistical Package for
Social Science (SPSS) software, Version 25.
Mean and standard deviation will be calculated for quantitative variables like age
(years), duration of pain (days) and frequency of pain before and after treatment, VAS
pain score before and after treatment in both groups. Frequency and percentages will be
calculated for categorical variables like gender, age in groups, residence, educational
status, employment status, side of pain, severity of pain before and after treatment,
safety and efficacy of treatment in both groups. Efficacy will be compared between the
group by applying chi-square test. Effect modifiers like gender, age in groups,
residence, educational status, employment status, duration of pain in groups and side of
pain will be controlled by stratification. Post-stratification chi-square test will be
applied by taking p value ≤ 0.05 as significant.