Received: 3 November 2023 | Revised: 13 March 2024 | Accepted: 17 March 2024

DOI: 10.1002/cre2.882

REVIEW ARTICLE

Compared to oxcarbazepine and carbamazepine, botulinum

toxin type A is a useful therapeutic option for trigeminal
neuralgia symptoms: A systematic review

Yeganeh Naderi1 | Maryam Rad1 | Ali Sadatmoosavi2 | Elham Khaleghi2 |

Zahra Khorrami3 | Goli Chamani4 | Mohammad Shabani5

1
Oral and Dental Diseases Research Center,
Kerman University of Medical Sciences, Abstract
Kerman, Iran
Objectives: This review aimed to compare the effectiveness of three treatments: BTX
2
Research Center for Modeling in Health,
Kerman University of Medical Sciences,
A, CBZ, and OXB, in managing trigeminal neuralgia (TN).
Kerman, Iran Material and Methods: We conducted a thorough search for research articles
3
Ophthalmic Epidemiology Research Center, related to our issue using specific keywords on several databases, including
Research Institute for Ophthalmology and
Vision Science, Shahid Beheshti University of Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed,
Medical Science, Tehran, Iran Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus
4
Department of Dental Medicine, Karolinska was on publications from 1965 to 2023.
Institute, Scandinavian Center for Orofacial
Neuroscience (SCON), Huddinge, Sweden Results: We retrieved 46 articles from the search and reviewed them carefully.
5
Neuroscience Research Center, Out of these, we selected 29 articles that met the inclusion criteria. Among the
Neuropharmacology Institute, Kerman
selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored
University of Medical Sciences, Kerman, Iran
the impact of BTX A on the improvement of TN symptoms. The response rate
Correspondence ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB.
Goli Chamani, Division of Oral Diagnostics and
Rehabilitation, Department of Dental
The response rate for BTX A ranged between 51.4% and 100%. All these three
Medicine, Karolinska Institutet, Scandinavian treatments had a remarkable effect on the improvement of TN. Importantly,
Center for Orofacial Neuroscience (SCON)
Huddinge, Sweden.
findings highlighted that side effects of CBZ and OXB could lead to treatment
Email: goli.chamani@ki.se discontinuation in some cases, whereas BTX A's side effects have been minimal
Mohammad Shabani, Neuroscience Research and less frequent.
Center, Neuropharmacology Institute, Kerman
University of Medical Sciences, Kerman, Iran. Conclusions: Consequently, BTX A emerges as a promising alternative for TN treatment.
Email: shabani@kmu.ac.ir and shabanimoh@ However, additional clinical trials are necessary to validate this finding, and further
yahoo.com
research is required to establish a standardized protocol for administering BTX A in TN.
Funding information
None KEYWORDS
botulinum toxin type A, carbamazepine, oxcarbazepine, trigeminal neuralgia

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2024 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Clin Exp Dent Res. 2024;10:e882. wileyonlinelibrary.com/journal/cre2 | 1 of 16

https://doi.org/10.1002/cre2.882
2 of 16 | NADERI
1 | INTRODUCTION
The hallmark of trigeminal neuralgia (TN) is abrupt, excruciating
pain (Wu et al., 2012). The disease presents as short, persistent,
and chronic unilateral attacks of pain in the face, usually on the
right side (Merskey, 1994). This pain can last from 1 s to about
2 min (Society, 2004) and spreads along the nerve branches,
especially the maxillary and mandibular branches (Chithralekha &
MS, 2018). Sudden attacks of pain are triggered by stimuli that
are usually not painful, such as talking, chewing, or brushing the
teeth. These attacks do not threaten a person's life, but the
frequency of attacks can effectively reduce a person's quality of
life (Yang et al., 2018).
TN is often undiagnosed or misdiagnosed. Outbreaks have
been reported in various studies having a range of 4.3–27 new
cases per 100,000 people (Katusic et al., 1990; MacDonald, 2000;
Mueller et al., 2011). It affects older people by a higher
percentage (Shaikh et al., 2011). Women are twice as likely to
be impacted as men (Katusic et al., 1990). Its lifetime prevalence
in the study populations is estimated between 0.16% and 0.3%
(Mueller et al., 2011; Sjaastad & Bakketeig, 2007). Ages 53 and
43, respectively, are the average onsets of classic and secondary
TN, while people can develop the disease at any age, from youth
to old age (De Simone et al., 2005; Maarbjerg et al., 2014). The
cause of TN is still unknown. According to one of the hypotheses,
the reason behind this is that the trigeminal nerve's entrance is
being compressed by a cerebral artery (Katusic et al., 1990).
Evidence of demilitarization and remilitarization has been
provided using electron microscopy. It can also occur secondary
to tumors and multiple sclerosis (De Santi & Annunziata, 2012;
Nurmikko et al., 2010). According to the new classification, TN is
separated into two groups: primary (idiopathic and classical) and
secondary (symptomatic), depending on the underlying cause
(Bendtsen et al., 2019). In acute exacerbations of attacks,
intravenous injection of fosphenytoin or lidocaine can be used,
and in case of long‐term treatment, carbamazepine (CBZ) or
oxcarbazepine (OXB) are suggested as first‐choice medications.
Lamotrigine, gabapentin, botulinum toxin type A (BTX A),
pregabalin, baclofen, and phenytoin are alternative treatments.
Surgical option is recommended when drug treatment is no longer
effective or tolerable (Bendtsen et al., 2019).
1.1 | Carbamazepine
Carbamazepine is a sodium channel blocker that is considered the
first line of treatment for TN (Maarbjerg et al., 2017). CBZ can reduce
the severity and frequency of TN attacks. However, the effectiveness
of the drug introduced by the U.S. Food and Drug Administration is
limited by poor tolerability (Wiffen et al., 2011). Long‐term and high‐
dose use of the drug can result in side effects such as dizziness,
drowsiness, leukopenia, diplopia, hyponatremia, and impaired vitamin
D metabolism (Keränen & Sivenius, 1983).
ET AL.
1.2 | Oxcarbazepine
OXB is a keto CBZ derivative that is quickly absorbed after oral
administration. It is prescribed in many cases as the first line of classical
TN treatment. Due to its high tolerance and minimal drug interactions,
OXB is effective in individuals who are also taking other medications to
treat their medical condition. (Jorns & Zakrzewska, 2007). The
gastrointestinal tract and central nervous system are the most
frequently affected areas by OXB adverse effects, which include
diplopia, fatigue, drowsiness, dizziness, nausea, vomiting, and rash (Fang
& Gong, 2015). Also, due to the risk of developing hyponatremia, high
doses should be used with caution, and it should be noted that due to its
similarity to CBZ, it can cause allergies in people allergic to CBZ (Jorns &
Zakrzewska, 2007).
1.3 | Botulinum toxin A
BTX A is a potent neurotoxin generated by the bacterium Clostridium
botulinum, which inhibits acetylcholine from being released at
neuromuscular synapses and results in paralysis of muscles (Sandrini
et al., 2017). The conventional use of this toxin involves affecting
muscle contraction by entering the presynaptic terminals at the
neuromuscular junction. Type A botulinum toxin specifically interacts
with SNAP‐25, a vital protein in acetylcholine release, while Type B
binds to synaptobrevin or VAMP, preventing release into the synaptic
space. However, this established mechanism does not adequately
explain the pain‐relieving effects of botulinum toxin on conditions
like TN, other forms of neuropathic pain, or migraines (Aurora, 2006;
Castillo‐Álvarez et al., 2017).
In the treatment of TN, BTX A can be beneficial through its analgesic
effects. The pain‐relieving properties of BTX A are associated with
multiple mechanisms. In addition to its confirmed ability to inhibit
acetylcholine exocytosis, there is evidence suggesting that BTX A may
also prevent the release of different neurotransmitters, which can
potentially limit muscle spindle discharge and sympathetic transmission.
This impact has been associated with the inhibition of norepinephrine and
ATP release, both integral to the process of chronic pain development.
Furthermore, the inhibition of substance P release has been implicated,
with its heightened presence in the spinal cord contributing to central
sensitization—a mechanism crucial to BTX A's analgesic efficacy,
particularly in addressing primary headaches (Mense, 2004; Mittal
et al., 2016; Verma, 2013). Moreover, other neurotransmitters linked to
the pain‐relieving effects of BTX A play a role in anti‐inflammatory
mechanisms. Peptides associated with the calcitonin gene and glutamate
are released together in the Gasser ganglion through calcium channel‐
dependent mechanisms and implicated in migraines; in both cases, their
release is inhibited by the local administration of botulinum toxin
(Ashkenazi & Blumenfeld, 2013; Chan & MaassenVanDenBrink, 2014;
Meng et al., 2018).
TN is regarded as one of the most agonizing pains known to
mankind, which is very difficult to diagnose and treat. OXB and CBZ
have been shown to have a very significant effect on the treatment of
NADERI ET AL. | 3 of 16

TABLE 1 Inclusion and exclusion criteria for the systematic review.

Inclusion criteria Exclusion criteria

A comparison/control group or the sample included CBZ, OXB, or BTX A CBZ, OXB, or BTX A were not included in
comparison/control or sample group

Published before 2024 Duplications

Type of publication: review articles, systematic reviews, briefs, conference Dissertations and unpublished documents
presentations, etc.

Directly related to the treatment of TN Not written in English

Available full‐text of publication

Abbreviations: BTX A, botulinum toxin A; CBZ, carbamazepine; OXB, oxcarbazepine; TN, trigeminal neuralgia.

TN as the first line of treatment. On the contrary, BTX A has drawn a TABLE 2 Modified Jadad scores scale.
lot of interest in the course of therapy for this disease recently, and Item Points
according to studies, it has caused few side effects. No clear results
Randomization Appropriate 2
have been found on the superiority of any of these therapies over
Did not describe the details of 1
each other, nor have any studies compared the effects of BTX A with
randomization
CBZ and OXB (Table 1) in clinical trials. At the same time, no
systematic article was found comparing these treatments specifically. Inappropriate 0

Therefore, we systematically reviewed the literature to compare Concealment Appropriate 2

them. Did not describe the details of 1
concealment

Inappropriate or no concealment 0
2 | MATERIALS AND METHODS
Blinded Appropriate 2

2.1 | Search strategy Did not describe the details of 1

blinded

This research was performed in compliance with the systematic Inappropriate or not blinded 0

review guidelines recommended by the Cochrane Collaboration. The
PICO was used to formulate the research question (Patient/Problem,
Intervention, Compared to, and Outcome) format. The subjects with
TN comprised the research population. The intervention consisted of
a prescription for BTX A and/or CBZ and/or OXB; the comparison
(Table 2) was between individuals who received treatment with BTX
A and patients treated with CBZ and/or OXB with an untreated
patient cohort or control group, and the subjects' clinical status
improved as a result of the study, including reduction in the intensity
and frequency of paroxysmal attacks of pain. The search was
undertaken across six electronic databases (i.e., Web of Science,
Scopus, PubMed, Embase, Ovid, and EBSCO) systematically.
Thesauri were used to identify the primary keywords in both
singular and combined forms following the preliminary evaluations,
such as medical subject headings (MeSH) and Emtree, and then the
appropriate search strategy was developed based on the database.
For every segment of the research question, general keywords were
chosen, and synonyms were added to the search. Combinations of
keywords were added to the selected subject‐specific databases,
placing “AND” in between the primary keywords and “OR” between
synonyms. The databases were searched from 1996 to 2023, with no
time limit.
The following search phrases were used to find primary studies
in different databases: (Carbamazepine OR Epitol OR Tegretol OR
Withdraw or drop‐out Described 1
Did not describe 0
Finlepsin OR Neurotol OR Amizepine OR Carbamazepine Acetate OR
Carbamazepine Dihydrate OR Carbamazepine Hydrochloride OR
Carbamazepine L‐Tartrate (4:1) OR Carbamazepine Anhydrous
OR Carbamazepine Sulfate (2:1) OR Carbamazepine Phosphate OR
Carbazepin), AND (Oxcarbazepine OR Trileptal OR Timox OR GP
47680 OR N‐Formyl‐10‐oxo‐10,11‐dihydro‐5H‐dihydro[b,f]azepine‐
5‐carboxamide) AND (Botulinum Toxin A OR Toxin A, Botulinum OR
Botox OR Neuronox OR Oculinum OR Clostridium Botulinum Toxin
Type A OR Botulinum Neurotoxin A OR Neurotoxin A, Botulinum OR
OnabotulinumtoxinA OR Meditoxin OR Vistabex), AND (Trigeminal
Neuralgia OR Neuralgia, Trigeminal OR Trigeminal Neuralgias OR Tic
Douloureux OR Trifacial Neuralgia OR Neuralgia, Trifacial OR
Trifacial Neuralgias OR Fothergill Disease OR Disease, Fothergill
OR Idiopathic Trigeminal Neuralgia OR Trigeminal Neuralgia, Idio-
pathic OR Neuralgia, Idiopathic Trigeminal OR Idiopathic Trigeminal
Neuralgias OR Secondary Trigeminal Neuralgia OR Neuralgia,
Secondary Trigeminal OR Trigeminal Neuralgia, Secondary OR
Secondary Trigeminal Neuralgias OR Epileptiform Neuralgia OR
Epileptiform Neuralgias OR Neuralgia, Epileptiform).
4 of 16 | NADERI
To increase the sensitivity of our search, we also searched the
reference lists or bibliographies of all pertinent papers and reports of
current networks, pertinent organizations, and conferences.
2.2 | Study selection
In the next step, the text documents containing the data found
from the chosen databases (2654 articles in sum) were brought
into EndNote X9 (Thomson Reuters) and imported into an Excel
spreadsheet to look for duplicates and as a preliminary screening.
Duplicates were removed. Inclusion criteria were studies reporting
the effects of CBZ, OXB, and BTX A on TN. There were no
restrictions on the kind of report (published, unpublished, briefs,
conference presentations, etc.). Articles that were not written in
English and whose data were not reachable were excluded (Table 1
shows the criteria for inclusion and exclusion). Two independent
reviewers (YN and EKH) screened titles, abstracts, and main text
for selection. If there was any difference of opinion among the
reviewers, an arrangement was reached through consultation with
the statistical advisor and the third reviewer, who is also an
epidemiologist (MR). To assess the articles' quality, a numerical
scale‐based method was employed. For evaluating the caliber of
the randomized trials, the Jadad scale was employed and was
developed for pain research. This scale presented very good
validity and reliability evidence (Olivo et al., 2008). The original
Jadad scale is a five‐point system. Because inadequate conceal-
ment of therapeutic allocation has been linked to an amplification
of treatment effects, we decided to use a modified Jadad score
scale, which provides a maximum of 2 points for concealment
(Balasubramanian et al., 2006; Jiang et al., 2011). The Jadad scale
score ranges from 1 to 7, which determines the quality of
randomized controlled trials (RCTs). If the modified Jadad score
is greater than 4, the study is considered of high quality. On the
contrary, if the score is between 3 and 4, it is of moderate quality.
Finally, if the score is less than 3, the study is considered of low
quality. To assess the methodological quality of RCTs in a
systematic review, a modified scale was used, incorporating
questions as outlined in Table 2 (Chen et al., 2014).
All trials were evaluated using this checklist as a guide to identify
the ones of superior quality. Articles receiving a grade greater than 3
were included in the study. To address the variability in the
evaluation of recovery indicators, drug dosages, control groups, and
duration of follow‐up periods in RCTs, we have incorporated
retrospective studies that assessed CBZ, OXB, or BTX A as a
comparison group. These studies provide valuable information,
especially concerning the adverse effects of the medications, which
can enhance the comprehensiveness of our research. For this
purpose, the Newcastle‐Ottawa Scale (NOS) was employed to assess
nonrandomized studies' quality. It is a “star system” in which a study
is judged based on three perspectives: the choice of study groups, the
ability to compare groups, and to determine the exposure or outcome
(Wells et al., 2000).
ET AL.
2.3 | Data extraction
Subsequently, the necessary data were separately extracted and
added to Excel 2010 (Microsoft Corp.) through two reviewers (YN
and GCh) according to a form designed to collect data, and after that,
the third author assessed it (MR). Name of the principal author,
publishing date, the study's quality assessment rating, type of study,
sampling strategy, sample size, study group assignments, length of
treatment, follow‐up duration, the drug dosage, age (average, range),
gender ratio, response of the patient to treatment, kind of treatment
intervention, clinical results, and complications were all methodically
documented. In the occurrence of heterogeneity, we could not
perform a meta‐analysis.
3 | RESULTS
As indicated in Figure 1, 2654 studies were identified from the
database search. Of the total records, 756 articles were eliminated
after being determined to be duplicates, resulting in 1493 records.
Articles not written in English and their data were not available
(n = 396) were excluded. After excluding nonrelevant articles
according to abstracts and titles, 52 full‐text articles were assessed
for eligibility. Following the assessment, case reports (n = 2)
(Bataglion et al., 2009; Zakrzewska & Patsalos, 1989), cohort studies
(n = 2) (Caldera et al., 2018; Wu et al., 2019) and one review article
(Besi et al., 2015) were not included in the research. Additionally, due
to the unavailability of the full texts, four articles were eliminated
(Debta et al., 2018; Hassan et al., 2013; Liebel et al., 2001; Wang &
Li, 2021), eight articles were excluded due to descriptive nature
(Ariyawardana et al., 2012; Ayele et al., 2020; Baykal & Kaplan, 2010;
Faryabi & Joolhar, 2014; Shah et al., 2013; Taylor et al., 1981;
Vilming et al., 1986; Zakrzewska et al., 2018), two articles did not
show qualified outcomes (LLOYD‐SMITH & Sachdev, 1969;
Nicol, 1969), and four articles did not explore what we were looking
for (Ricciardi et al., 2021; Song et al., 2021; Zhang et al., 2020, 2021).
Subsequently, 29 articles remained and were assessed by two
authors (YN and EKH) separately.
3.1 | CBZ and OXB effects
Among the 29 selected articles, 11 studied the effects of CBZ and
OXB on the improvement of TN (Ariyawardana et al., 2003; Campbell
et al., 1966; Di Stefano et al., 2014, 2021; Gomez‐Arguellese
et al. 2008; Lechin et al., 1989; Lemos et al., 2010; Puri et al., 2018;
Shaikh et al., 2011; Tariq et al., 2021; Verma et al., 2014; Yadav
et al., 2015). A total of 1029 patients had been studied. The oldest
article was related to 1966 (Campbell et al., 1966), and the latest was
related to 2021 (Di Stefano et al., 2021; Tariq et al., 2021). The age
range of patients was 20–84 years. The minimum sample size
included 21 (Shaikh et al., 2011), and the maximum included 354
patients (Di Stefano et al., 2021). The shortest follow‐up period was
NADERI ET AL.
FIGURE 1 Studies considered for inclusion in the systematic review.
1 month (Puri et al., 2018; Tariq et al., 2021), and the longest was
87.72 months (Di Stefano et al., 2014). The lowest dose of CBZ was
100 mg (Ariyawardana et al., 2003; Tariq et al., 2021), and the highest
was 1200 mg (Di Stefano et al., 2014, 2021; Lechin et al., 1989;
Lemos et al., 2010; Tariq et al., 2021). The lowest dose of OXB was
300 mg (Di Stefano et al., 2021), and the maximum dose was 1800
mg (Di Stefano et al., 2014, 2021). The recovery index in several
articles was a percentage of recovery (Ariyawardana et al., 2003;
Campbell et al., 1966; Di Stefano et al., 2014, 2021; Gomez‐Arguelles
et al., 2008; Lechin et al., 1989; Yadav et al., 2015), and in some of
them was decreasing in the frequency of attacks (Campbell
et al., 1966; Di Stefano et al., 2021; Gomez‐Arguelles et al., 2008;
Lemos et al., 2010). The other indexes were a decrease in the degree
of pain as indicated by the standard visual analog scale (VAS) (De
Simone et al., 2005; Di Stefano et al., 2014; Puri et al., 2018; Tariq
et al., 2021), numeric rating scale (NSR) (Lemos et al., 2010), Likert's
numerical scale, and the faces rating scale developed by Wong‐Baker
| 5 of 16
(Verma et al., 2014) (Tables 3 and 4 present the studies which
examined the effects of CBZ and OXB).
3.2 | Botulinum toxin A effect
The remaining 18 articles examined the impact of BTX A (Table 4) on
TN symptom improvement (Bohluli et al., 2011; Crespi et al., 2019;
Gazerani et al., 2009; Gorimanipalli et al., 2019; Jorns et al., 2019;
Li et al., 2014; Liu et al., 2018; Piovesan et al., 2005; Shehata
et al., 2013; Türk Börü et al., 2017; Wu et al., 2012; Xia et al., 2016;
Yoshida, 2020, 2021; Zhang et al., 2014, 2017, 2019; Zuniga
et al., 2008). A total of 729 patients had been examined. The oldest
article was related to the year 2005 (Piovesan et al., 2005), and the
latest was related to the year 2021 (Yoshida, 2021). The patients'
ages ranged from 23 to 91 years. The minimum sample size included
10 (Crespi et al., 2019; Yoshida, 2020), and the maximum included
6 of 16 | NADERI ET AL.

TABLE 3 Basic information on CBZ and OXB in patients with TN is included in this systematic review.

Study design Country Mean age (sd) Range age Reference

RCT United Kingdom 59 20–84 Campbell et al. (1966)

Double‐blind crossover trial Venezuela 59.3 48–68 Lechin et al. (1989)

Retrospective Sri Lanka – 26–83 Ariyawardana et al. (2003)

Crossover (open‐label) Spain 62.2 ± 16.7 32–84 Gomez‐Arguelles et al. (2008)

Parallel double‐blind RCT Portugal 64 ± 12.5 Lemos et al. (2010)

68 ± 10.7

Crossover clinical trial Malaysia 64.6 ± 13.2 32–84 Shaikh et al. (2011)

– India – 41–78 Verma et al. (2014)

Retrospective Italy 67.5 ± 12.1 – Stefano et al. (2014)

Retrospective India 54.9 34–76 Yadav et al. (2015)

RCT India – 48–80 Puri et al. (2018)

Retrospective Italy 66 29–89 Di Stefano et al. (2021)

Comparative perspective Pakistan 54.7 ± 8.4 38–70 Tariq et al. (2021)

152 patients (Zhang et al., 2019). The shortest duration of follow‐up
was a week (Gazerani et al., 2009), and the longest was 28 months
(Zhang et al., 2019). The lowest injected dose was 20 units (Zuniga
et al., 2008), and 200 units was the optimum injection dosage (Liu
et al., 2018).
The recovery index in several articles was recovery percentage
(Gorimanipalli et al., 2019; Li et al., 2014; Türk Börü et al., 2017; Wu
et al., 2019; Zhang et al., 2014, 2017), and in some of them was a
reduction in frequency of attacks (Crespi et al., 2019; Jorns
et al., 2019; Lechin et al., 1989; Shehata et al., 2013; Türk Börü
et al., 2017; Yoshida, 2021; Zhang et al., 2017) and several articles
were decreased in the severity of the pain measured via VAS criteria
(Bohluli et al., 2011; Gorimanipalli et al., 2019; Li et al., 2014; Liu
et al., 2018; Piovesan et al., 2005; Shehata et al., 2013; Türk Börü
et al., 2017; Wu, et al., 2012; Xia et al., 2016; Yoshida, 2020, 2021;
Zhang et al., 2014, 2017, 2019; Zuniga et al., 2008). NSR was the
recovery index in one article (Jorns et al., 2019). According to the
articles that examined repeated injection of BTX A, no significant
difference was obtained if the injection was repeated (Zhang
et al., 2014; Zhang et al., 2017) (Tables 5 and 6 present the studies
that examined the effects of CBZ and OXB).
3.3 | Side effects
The central nervous system and gastrointestinal tract were the most
frequently observed CBZ adverse reactions. Nausea (Ariyawardana
et al., 2003; Puri et al., 2018; Tariq et al., 2021) and vomiting (Puri
et al., 2018) were the most common side effects associated with the
gastrointestinal tract and dizziness (Ariyawardana et al., 2003; Di
Stefano et al., 2014, 2021; Puri et al., 2018; Shaikh et al., 2011; Tariq
et al., 2021), motor coordination impairment (Lechin et al., 1989),
headache (Lemos et al., 2010; Puri et al., 2018), drowsiness
(Ariyawardana et al., 2003; Campbell et al., 1966; Tariq et al., 2021),
confusion and unbalance (Campbell et al., 1966; Di Stefano
et al., 2014, 2021), muscle ataxia (Tariq et al., 2021), diplopia,
lethargy, numbness of extremities (Tariq et al., 2021), fatigue,
sedation (Puri et al., 2018), and somnolence (Di Stefano
et al., 2014, 2021) were the most common complications associated
with the central nervous system. Hepatic (Campbell et al., 1966; Di
Stefano et al., 2021; Shaikh et al., 2011), renal (Shaikh et al., 2011),
and hematopoietic complications, including anemia (Di Stefano
et al., 2014, 2021), agranulocytosis (Campbell et al., 1966), leukope-
nia (Ariyawardana et al., 2003; Di Stefano et al., 2021; Di Stefano
et al., 2014), and thrombocytopenia (Campbell et al., 1966; Di
Stefano et al., 2021), caused by this drug have also been reported.
Inadequate secretion of vasopressin resulting in a decrease in
water excretion (Ariyawardana et al., 2003), increased secretion of
transaminase and gamma‐glutamyl transferase (Campbell et al., 1966;
Di Stefano et al., 2021), and skin allergy reactions were also reported
(Campbell et al., 1966; Di Stefano et al., 2021; Lechin et al., 1989;
Shaikh et al., 2011). Considering these adverse effects on the central
nervous system (often occurring together) (Di Stefano et al., 2021),
hyponatremia (Di Stefano et al., 2021), leukopenia (Ariyawardana
et al., 2003), and skin rash (Campbell et al., 1966) caused treatment
interruption.
Side effects of OXB are reported in order of prevalence as
follows: hyponatremia (Di Stefano et al., 2014, 2021; Gomez‐
Arguelles et al., 2008), somnolence (Di Stefano et al., 2014, 2021;
Gomez‐Arguelles et al., 2008), postural unbalance (Di Stefano
et al., 2014, 2021), dizziness (Di Stefano et al., 2014, 2021;
Gomez‐Arguelles et al., 2008), and complications such as liver
dysfunction (Di Stefano et al., 2021), vomiting (Gomez‐Arguelles
et al., 2008), nausea (Gomez‐Arguelles et al., 2008), thrombocytope-
nia (Di Stefano et al., 2014, 2021), headache, and muscle ataxia
(Gomez‐Arguelles et al., 2008). Also, allergic skin reactions caused by
TABLE 4 Comparison of the effects of CBZ and OXB with control drugs in selected articles in patients with TN.
NADERI

SS: (CBZ Follow‐up

Or OXB) SS SS: (Comparative groups) (month) Drug dosage Improvement criteria Reference
ET AL.

36 (CBZ) 70: 34 (placebo lactose) 2 Half a tablet four times daily, and if relief was The CBZ group improved 68% in the first period, Campbell
m = 24, insufficient after 48 h, it could be increased and the placebo group only 26%. et al. (1966)
f = 46 to 1 tablet four times daily.

48 (CBZ) 48 48 (pimozide) 6 CBZ = 300 to 1200 mg daily, pimozide = 4 to pimozide‐treated patients' improvement was Lechin et al. (1989)
24 = m, 12 mg daily 100% and for CBZ—the treated group
24 = f was 56%.

50 (CBZ) 61: 11 (phenytoin sodium, sodium 4 CBZ alone initial dose: 100 mg three times 62% of 50 patients initially treated with CBZ Ariyawardana
26 = m, valproate, and amitriptyline) a day or 200 mg three times a day alone had significant pain control within a et al. (2003)
35 = f month; however, in the long term, treatment
with CBZ alone was effective in only 29.5%
of patients. The response rate of the patients
treated with various combinations of CBZ
and other drugs was 64% within a month.

35 (OXB) 35 – 3 mean maintenance dose = 773.7 mg/day There was a significant reduction in pain Gomez‐Arguelles
7 = m, frequency, leading to improvements in et al. (2008)
28 = f patient satisfaction. In general, OXB was well
tolerated.

24: 9 = m 45 21 (CBZ associated with the 5 Protocol 1: CBZ + ROP = 2 mL of a 2 mg/mL Both protocols resulted in a decrease in pain Lemos et al. (2010)
15 = f peripheral analgesic block ROP and CBZ dose of 400–1000 mg/day, intensity and number of pain crises.
using ropivacaine (ROP)), Protocol 2: CBZ = between 400–600 and CBZ + ROP showed a significantly stronger
3 = m, 18 = f 1000–1200 mg/day reduction in pain intensity.

21 CBZ 21 21 Lamotrigine (LTG)) – LTG = 400 mg CBZ benefitted 90.5% (19/21) of the patients Shaikh et al. (2011)
9 = m, 12 = f CBZ = 1200 mg with pain relief in contrast to 62% (13/21)
from LTG.
VAS: 13 patients gained pain relief from LTG and
19 from CBZ, 77% (10/13) obtained a
complete degree of pain relief from LTG, as
compared with 21% (4/19) from CBZ.

20 (CBZ) 40 20 (duloxetine) 11 = m, 9 = f 2 Duloxetine = 20 mg Duloxetine is as effective as CBZ in the Verma et al. (2014)
12 = m, 8 = f CBZ = 200 mg treatment of TN.

95 CBZ 178: 83 OXB 87.72 CBZ = 600 mg (range 200–1200) The initial number of responders was 98% with Di Stefano
68 = m, OXB = 1200 mg (range 600–1800) CBZ and 94% with OXC. et al. (2014)
132 = f In a mean period of 8.6 months, 27% of
responders to CBZ discontinued treatment or
dosage due to side effects. In a mean period
of 13 months, the same occurred to 18% of
|

responders to OXB.

(Continues)
7 of 16
TABLE 4 (Continued)
8 of 16

SS: (CBZ Follow‐up

|

Or OXB) SS SS: (Comparative groups) (month) Drug dosage Improvement criteria Reference

69 CBZ 72: 27 (CBZ and gabapentin), 21 36 – CBZ: highly effective in 60.8% of the cases on a Yadav et al. (2015)
23 = m, (alcohol block) long‐term basis with maintenance doses in
49 = f 19 (peripheral neurectomy) idiopathic TN. Other treatment modalities
5 (CBZ after surgery), 4 (referred employed in more refractory cases include
neurologist) the add‐on of gabapentin, neurolytic alcohol
blocks, and peripheral surgical intervention.

15 CBZ: 45 15 (baclofen) 1 CBZ = 600–800 mg/day CBZ combined with baclofen is most effective in Puri et al. (2018)
7=m 5 = m,10 = f CBZ and baclofen = 600 mg/day and baclofen alleviating pain in TN when compared with
8=f 15 (capsaicin) 10–20 mg/day CBZ alone or the CBZ capsaicin combination.
6 = m,9 = f CBZ and capsaicin = 600 mg/day plus 25%
capsaicin.

179 CBZ 354: 175 OXB 12 CBZ = classical, secondary and idiopathic: The initial proportion of responders was 88.3% Stefano et al. (2021)
125 = m, 600 mg (range 200–1200) with CBZ and 90.9% with OXB.
229 = f OXB = classical: 1200 mg (range 300–1800) In 29.6% of patients treated with carbamazepine
Secondary: 1200 mg (range 600–1800) and 12.6% of patients treated with OXB,
Idiopathic: 900 mg (range 300–1800) major side effects caused discontinuation of
treatment or dose reduction to an
unsatisfactory level.

30 CBZ 60: 30 Topiramate: 9 = m, 21 = f 1 CBZ: 100–1200 mg/day Topiramate has comparable efficacy as CBZ with Tariq et al. (2021)
12 = m, 21 = m, Topiramate: 25–400 mg/day fewer side effects
18 = f 39 = f

Abbreviations: CBZ, carbamazepine; OXB, oxcarbazepine; SS, sample size; TN, trigeminal neuralgia.
NADERI
ET AL.
NADERI ET AL. | 9 of 16

TABLE 5 Basic information on patients with TN in BTX A studies is included in this systematic review.

Study design Country Mean age (sd) Range age Reference

Open‐Label Study Brazil F = 59.2 ± 14.2 M = 67.7 ± 6.6 – Piovesan et al. (2005)

Open‐Label Study Brazil 58.5 28–91 Zuniga et al. (2008)

Placebo‐Controlled Trial Denmark 26.3 ± 2.6 23–32 Gazerani et al. (2009)

Preliminary Report Iran 48.9 28–67 Bohluli et al. (2011)

RCT Randomized Double‐Blind Placebo‐Controlled China 59.1 ± 12.5 30–82 Wu et al. (2012)
Trial

Randomized Single‐Blinded Placebo‐Control Egypt 45.9 ± 10 27–72 Shehata et al. (2013)

Randomized Double‐Blind Placebo‐Controlled Trial China 58.41 ± 11.74 31–78 Zhang et al. (2014)

Open‐Label Study China 60.6 ± 11.90 33–89 Li et al. (2014)

– China 60.8 37–89 Xia et al. (2016)

Open‐Label Study Turkey 54.8 ± 4.5 27–77 Türk Börü et al. (2017)

Open‐Label Trail China Single dose: 60.7 ± 10.8 – Zhang et al. (2017)
Pilot Study Repeated dose:57 ± 10.3

Pilot Study China Older: 82.6 ± 2.9 80–90, 34–59 Liu et al. (2018)
Younger: 49.5 ± 6.3

Prospective Thailand 67.2 + 8.4 49–79 Jorns et al. (2019)

Open‐Label
Clinical Pilot Study

Open‐Label Study: Pilot Study Norway 59.4 ± 11.7 39–74 Crespi et al. (2019)

Retrospective India 52.59 ± 12 – Gorimanipalli et al. (2019)

Retrospective China F = 59, M = 60 F = 31–9, M = 39–8 Zhang et al. (2019)

Preliminary Japan 63.6 ± 13.7 40–80 Yoshida (2020)

Open‐Label Uncontrolled Study

Retrospective Japan 68.2 ± 13.6 – Yoshida (2021)

Abbreviations: BTX A, botulinum toxin A.; TN, trigeminal neuralgia.

OXB have been reported (Di Stefano et al., 2014, 2021). Causes of
treatment interruption were hyponatremia and central nervous
system side effects (Di Stefano et al., 2014, 2021; Gomez‐Arguelles
et al., 2008).
The most reported complications of BTX A were conceived to be
correlated to the injection approach and consisted of facial nerve
palsy and facial asymmetry (Bohluli et al., 2011; Crespi et al., 2019;
Gorimanipalli et al., 2019; Jorns et al., 2019; Li et al., 2014; Liu
et al., 2018; Piovesan et al., 2005; Shehata et al., 2013; Türk Börü
et al., 2017; Wu et al., 2012; Yoshida, 2021; Zuniga et al., 2008),
edema and swelling at the injection site (Crespi et al., 2019; Li
et al., 2014; Wu et al., 2012; Xia et al., 2016; Yoshida, 2021), muscle
weakness (Gazerani et al., 2009; Türk Börü et al., 2017; Xia
et al., 2016; Yoshida, 2021), jaw discomfort during maximal mouth
opening (Wu et al., 2012; Yoshida, 2021), tenderness, and pain at the
injection site (Yoshida, 2021). Complications such as hematoma at
the injection site (Shehata et al., 2013), dizziness (Jorns et al., 2019),
and discomfort in the whole body (Liu et al., 2018) were also
observed. Overall, the adverse reactions to BTX A were transient
while slight.
3.4 | Heterogeneity
In the event of the presence of heterogeneity in the evaluation of
recovery indices, drug dose, and follow‐up time after treatment, we
could not perform a meta‐analysis. Furthermore, the quantity of
clinical trial studies was constrained since there were no clinical trial
studies comparing botulinum toxin A with CBZ and OXB.
4 | D IS CU SS IO N
The review of the studies showed that CBZ, OXB, and BTX A had a
remarkable effect on the improvement of TN. There are many
available studies about the treatment of TN, but there are limited
available systematic reviews and meta‐analysis studies to compare
the treatment options of TN. A network meta‐analysis on eight drugs
(including BTX A, CBZ, and OXB) reviewed related studies up to
2014. This study showed that among the drugs studied, including
BTX A, lamotrigine, pimozide, tizanidine, CBZ, OXB, lidocaine, and
proparacaine, all drugs except pimozide and proparacaine were more
TABLE 6 Comparison of the effects of BTX A with the effects of control drugs in selected articles in patients with TN.
10 of 16

SS: BTX.A SS SS: Comparative groups Follow‐up (month) Drug dosage Improvement criteria Reference
|

13: 4 = m, 9 = f 13 3 V1: 6.83 U Pain intensity was significantly reduced at the first Piovesan et al. (2005)
V2: 6.45 U assessment after BTX A treatment and peaked
V3: 9.11 U on the 20th day.

12: 5 = m, 7 = f 12 2 20–50 U BTX A provides a very fast and long‐lasting benefit Zuniga et al. (2008)
for the management of both TN and probably
other similar conditions

14: 14 = m 14 Placebo 1 week 22.5 U BTX A reduces pain, neurogenic inflammation, and Gazerani et al. (2009)
Saline cutaneous heat pain threshold. No alteration
was recorded for electrical or pressure pain
thresholds

15: 8 = f, 7 = m 15 6 50 U BTX A is a minimally invasive method that can play Bohluli et al. (2011)
a role in treating TN before other more
invasive therapies, that is, radiofrequency and
surgery.

22: 19 = m, 13 = f 42 20 (placebo) 3 75U/1.5 mL Significantly more responders were present in the Wu et al. (2012)
10 = f,10 = m BTX A group (68.18%) than in the placebo
group (15.00%).

10 20 10 (placebo) 3 40 U (8 injection points) BTX A has a direct analgesic effect (significant Shehata et al. (2013)
9=m Normal saline to 60 U (12 points) decrease in the number of acute medications
11 = f and Paroxysm frequency/day) in patients
with TN.

25 (BTX‐A 25 U) 80 27 (placebo) 2 BTX A 25 U = 25 U/1 mL The response rates of the 25 U group (70.4%) and Zhang et al. (2014)
10 = m, 15 = f isotonic saline) BTX A 75 U = 75 U/1 mL the 75 U group (86.2%) were significantly
28 (BTX‐A 75 U) 14 = m, 13 = f higher than the placebo group (32.1%) at week
12 = m, 16 = f 8, and there was no significant difference
between the 25 U and 75 U groups.

88 (BTX.A) 88 14 Maximal and minimal doses Effective: within 1 month in 81 patients and at 2 Li et al. (2014)
38 = m, 50 = f were 170 U and 25 U, months in 88 patients (100%). The therapeutic
respectively. effect decreased: gradually after 3 months.
The prevalence of effective treatment at 14
months: 38.6%. Complete control of pain: 22
patients (25%). No significant difference
between different dose groups

87: 38 = m, 49 = f 87 2 Freeze‐dried BTX A 100 U/ The effective rates after 1, 2, 4, and 8 weeks of Xia et al. (2016)
bottle with 2 ml of 0.9% treatment were 48.28%, 66.67%, 78.16%, and
sodium chloride 80.46%, respectively. When compared to that
before treatment, the quality of life was
significantly better.
NADERI
ET AL.
TABLE 6 (Continued)
NADERI

SS: BTX.A SS SS: Comparative groups Follow‐up (month) Drug dosage Improvement criteria Reference
ET AL.

27: 6 = m, 21 = f 27 6 100 U BTX A BTX A significantly reduced pain intensity and Türk Börü et al. (2017)
pain attack frequency in the first week, second
month, and sixth month after treatment. In the
second month, 74.1% of patients, and in the
sixth month, 88.9% of patients responded to
treatment. Forty‐four percent of patients did
not experience any pain in the sixth month.

44: 19 = m, 25 = f 81 37 (repeated dose):
16 = m, 21 = f
6 single dose = 70–100 U
repeated dose (equal
volume 2 weeks later)
= 50–70 U
The response rate of the single‐dose group was Zhang et al. (2017)
61.4% and the repeated‐dose group was
51.4%. The groups were statistically similar in
TN frequency, time between treatment and
effect, time to peak effect, VAS scores, and
rates of adverse reactions (latency and
duration). However, the single‐dose group
experienced a significantly longer duration
of effect.

14: ≥80 years old 14 29 (comparative) 1 >80 years = 45–150 U Overall, BTX A is an effective and safe treatment Liu et al. (2018)
4 = m,10 = f 60 years old< (91.3 ± 25.6 U) for TN in patients with advanced age (≥80
10 = m, 19 = f <60 years = 30–200 U years old), at dosages similar to those used in
(71.8 ± 33.1 U) much younger counterparts (<60 years old).

13 13 7 25 U/1.5 mL Using botulinum injection with CBZ or OXB in Jorns et al. (2019)
patients with TN can reduce the severity of
pain, the frequency of pain attacks, and the
amount of medication taken compared to
using anticonvulsant drugs alone.

10: 7 = m, 3 = f 10 3 25 IU The reduction in the number of attacks was Crespi et al. (2019)
negative, but a significant reduction in the
intensity of the attacks and pain was observed.

23: 12 = m, 11 = f 23 3 (100 IU of BTX A, Allergan) The response rates of both groups were 100%. Gorimanipalli et al. (2019)
in 2.5 mL normal saline) The efficacy of injection was comparable in
3 IU/cm2 of pain area single injection and repeated injection groups.

152: 65 = m, 87 = f 152 28 Low‐dose group: <40 U The overall effective rate was 89.4%. Female Zhang et al. (2019)
Medium‐dose group: gender, short period of illness, and high
40–70 U injection dose (more than 70 units) were
High‐dose group: >70 U associated with lower long‐term VAS scores.

(Continues)
|
11 of 16
12 of 16 | NADERI ET AL.

effective than placebo. CBZ, lidocaine, and BTX A showed the

greatest effect on TN and can be prescribed as TN's primary stage of
therapy (Yang et al., 2018).
Yoshida (2020)

Yoshida (2021)
TN does not respond to common pain relievers, and antic-
onvulsants are used primarily to treat TN. Through the inhibition of
Reference

ectopic discharge at the disrupted membrane, a number of antic-

onvulsants have been reported to stabilize the plasma membrane of
peripheral nerve fibers. In 70% of patients, CBZ is the most efficient
complete recovery) at the endpoint was 86.8%

between the number of injected sites and the

The visual analog scale score and pain frequency

anticonvulsant and is frequently prescribed for managing TN (Baykal

A significant negative correlation was observed

The mean improvement (0%, no effect; 100%,

& Kaplan, 2010). Despite being the first medication of choice for
77.5% ± 13.8 % after 4 weeks, and all
subjective improvement achieved was
decreased significantly (p < .001). The

treating TN patients, CBZ has a variety of undesirable effects that

patients responded to treatment.

improvement of the VAS at the may make it inappropriate for many patients. For this reason,
additional medications like phenytoin, gabapentin, valproic acid,
clonazepam, lamotrigine, and topiramate have been applied for the
management of TN (Yoshida, 2021; Zhang et al., 2019).
endpoint (p < .005)
Improvement criteria

OXB is a 10‐keto analog of CBZ used to treat seizures and

neuropathic pain. According to certain studies, OXB is a tolerable and
efficacious strategy for various types of neuropathic pain (Carrazana
for TN.

& Mikoshiba, 2003). It has also been shown that OXB is effective in
most TN patients and is prescribed in many cases as the first
treatment option (Beydoun et al., 2002). Two open‐label studies have
shown that OXB notably reduces pain linked with TN, with fewer
clinical complications than CBZ (Di Stefano et al., 2021; Gomez‐
Arguelles et al., 2008). It is particularly effective for those who didn't
respond well to CBZ previously, as it can relieve pain (Zakrzewska &
Drug dosage

Patsalos, 1989). Additionally, in a study that we were unable to

43.1 ± 5.3 U

systematically review due to the unavailability of the full text despite

50 U

contacting the author, two drugs, CBZ and OXB, were compared and
it was found that in almost all of the patients of both groups, at least
a 50% reduction in the frequency of agonizing episodes occurred, and
in one‐half of those enrolled in both groups, the pain was entirely
Follow‐up (month)

controlled, which is why OXB was introduced as an effective drug

with better tolerance in idiopathic TN (Liebel et al., 2001). According
24.2 ± 9.1

to a meta‐analysis comparing OXB and CBZ in patients with

refractory TN, better tolerance and fewer side effects have also
been reported in patients receiving OXB, and OXB was found to be
3

Abbreviations: BTX A, botulinum toxin A; TN, trigeminal neuralgia.

an invaluable substitute therapy for TN patients (Beydoun

SS: Comparative groups

et al., 2002).
A review of clinical trials and open trials showed that CBZ was an
effective drug in TN patients' rehabilitation; nevertheless, its adverse
effects were high (Campbell et al., 1966; Di Stefano et al., 2014, 2021;
Gomez‐Arguelles et al., 2008; Lechin et al., 1989; Lemos et al., 2010;
Puri et al., 2018; Shaikh et al., 2011). In a study comparing CBZ and
OXB, the initial recovery rate was 98% for CBZ and 94% for OXB,
and in an average period of 8.6 months, side effects resulted in
discontinuation of treatment or dose reduction to undesirable levels
10

28
SS
(Continued)

in 27% of CBZ respondents. In an average of

13 months, the identical thing occurred to 18% of OXC respondents
(Di Stefano et al., 2014). Additional studies also suggested that
28: 23 = f, 5 = m
10: 2 = m, 8 = f

Gabapentin can be more effective (Baykal & Kaplan, 2010; Lemos

SS: BTX.A
TABLE 6

et al., 2010; Puri et al., 2018). Other investigations showed that CBZ
was more effective compared with pimozide (Lechin et al., 1989),
Lamotrigine (Shaikh et al., 2011), and tizanidine (Vilming et al., 1986),
NADERI ET AL.
while duloxetine and topiramate were comparable to CBZ in recovery
with fewer side effects (Tariq et al., 2021; Verma et al., 2014).
BTX A is currently known as a harmless and efficient medication
in TN management and has no major side effects. The effect of BTX A
has been evaluated in a number of clinical trials and open‐label
studies (Crespi et al., 2019; Gazerani et al., 2009; Jorns et al., 2019;
Li et al., 2014; Liu et al., 2018; Shehata et al., 2013; Türk Börü
et al., 2017; Wu et al., 2012; Zhang et al., 2014, 2017; Zuniga
et al., 2008), showing that it is a minimally invasive treatment that can
be used as a first‐line option and before other invasive treatments,
such as radiation therapy and surgery, in the treatment of TN.
Additionally, Piovesan et al. showed that BTX A can also reduce
preventive medication (including CBZ and OBX) by more than 50%,
stop them completely, or convert multiple medications to mono-
therapy (Piovesan et al., 2005).
Some studies have compared single‐dose with repeated injec-
tions and, in general, showed that regarding pain relief, there was no
noticeable distinction between the two groups (Zhang
et al., 2014, 2017). Conversely, Zhang et al. showed that additional
injections did not cause further BTX A side effects. On the other
hand, patients who received moderate or high doses of BTX A had a
higher complete treatment response than the low‐dose group,
indicating that the injection dose was efficient in terms of treatment
quality (Zhang et al., 2019).
Zhang and colleagues also discovered that there was no variance in
the incidence of BTX A injection adverse effects based on gender, age,
or injection dose. Nevertheless, the data demonstrated that the
incidence of adverse reactions is influenced by the number of branches
involved in the disease and its course; that is, individuals with moderate
disease length (1–10 months) and more branches involved are more
likely to have side effects (Zhang et al., 2019). Jorns and collaborators
demonstrated that the usage of BTX A injection in addition to CBZ or
OXB in patients with TN has the ability to lessen both the intensity and
the frequency of pain attacks ( Jorns et al., 2019).
In the current study, research reviews indicated that the adverse
effects of CBZ are great, and although OXB has fewer side effects
than CBZ, it can still cause major side effects and may lead to
discontinuation of treatment (Di Stefano et al., 2014, 2021; Gomez‐
Arguelles et al., 2008). The side effects of these two medications
remain a significant issue, in particular for those with idiopathic and
secondary TN. It is essential to develop better‐tolerated drugs (Di
Stefano et al., 2021).
Conversely, the adverse reactions to BTX‐A are mild and
temporary. However, in the present study, the heterogeneity of
studies performed in both groups in terms of factors such as the
type of study, follow‐up period, injection dose, and, most
importantly, the indicators that were evaluated for disease
recovery made it impossible to perform meta‐analysis, but in
general, BTX A seems to be an efficient medication with fewer
adverse effects than OXB and CBZ. Sampling methods, as well as
the improvement measures, were different in studies, and in
some articles, they were not mentioned. Therefore, one of the
limitations is that all of the articles included as part of this study
| 13 of 16
lack a single definition. The inability to access the full text, and in
some cases even the abstracts of related articles, is another
limitation of this research.
5 | CONCLUSION
As compared to CBZ and OXB, the study's findings suggested that
BTX A is an effective medication and has fewer adverse effects,
which can be recommended as a valuable substitute therapeutic
option for TN management. Currently, no clinical trial has been
conducted to compare the effectiveness of BTX A with CBZ and
OXB. There is also no standard protocol for the administration of BTX
A in TN. Thus, further clinical trials are required in the future to
confirm this conclusion.
6 | C L I N I C A L I M P L IC A T I O N S
Considering that the clinical treatment of TN with CBZ and OXB has
always been challenging, BTX A can help physicians manage TN as an
alternative with fewer side effects.
A UT H O R C O N T R I B U TI O NS
Yeganeh Naderi contributed to the study design, data collection, data
interpretation, and drafting of the manuscript. Maryam Rad con-
tributed to data collection, data analysis, and manuscript drafting. Ali
Sadatmoosavi, Elham Khaleghi, and Zahra Khorrami contributed to
data analysis, data interpretation, and drafting of the manuscript. Goli
Chamani and Mohammad Shabani contributed to the study concep-
tion, design, data collection, data interpretation, and manuscript
drafting.
ACKNOWLEDGME NT S
The authors have no funding to report.
CONFLIC T OF INTEREST STATEM ENT
The authors declare no conflicts of interest.
DATA AVAILABILITY STATEMENT
Upon request, the corresponding author will provide the data sets
used or analyzed in this study.
ETHIC S S TATEM ENT
All procedures were carried out in accordance with the ethical
guidelines established by the Kerman University of Medical Sciences
ethics committee.
C O D E A V A I L A B I L I TY S T A T E M E N T
This article includes all software applications that were used.
ORC I D
Mohammad Shabani http://orcid.org/0000-0002-2082-5849
14 of 16 | NADERI
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How to cite this article: Naderi, Y., Rad, M., Sadatmoosavi, A.,
Khaleghi, E., Khorrami, Z., Chamani, G., & Shabani, M. (2024).
Compared to oxcarbazepine and carbamazepine, botulinum
toxin type A is a useful therapeutic option for trigeminal
neuralgia symptoms: A systematic review. Clinical and
Experimental Dental Research, 10, e882.
https://doi.org/10.1002/cre2.882