Trigeminal neuralgia (TN) is a disease entity defined as “recurrent unilateral brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve and triggered by innocuous stimuli.” [1]. TN has been reported as one of the most painful disorder in the orofacial region, which has pain lasting from a second to few minutes [2]. Vascular compression of the trigeminal nerve has been known to be a major cause of TN, but TN can be also caused by either idiopathic conditions or lesions including cysts, tumors, and multiple sclerosis [3]. The diagnosis of TN is commonly established by clinically characterized feature, such as sudden severe facial pain rather than objective imaging studies, except only for the TN cases related to vascular compression [4]. Many cases of TN have thus frequently been misdiagnosed as other types of orofacial pain, which leads to unnecessary treatments for the patients [5].

For managing TN, most patients are commonly prescribed medications, and surgical interventions are also required in some cases [6]. However, paroxysmal attack and intractable pain are still challenging conditions for both physicians and patients. TN often presents with symptoms such as depression, anxiety, or sleep disorders resulting from chronic severe pain [7]. The daily activities of the patient are also affected, which degrades the quality of not only the patient’s life, but also that of their families. The frequent use of health care resources for the management of this disease also increases its socio-economic burden [8].

In clinical practice, the management of TN surpassed US $94 million in the United States between 2003 and 2013 [9]. TN is a rare disease and scant high-quality epidemiological data exist regarding this disease. There has yet to be consensus in the literature regarding the prevalence of TN, with only a few studies on a limited study group [10,11]. Thus, fundamental epidemiologic data are essential to establish the effective management of TN. The aim of this study was to identify the epidemiological features of TN, including incidence, regional distribution, and healthcare resource utilization based on the population data in Korea.

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This study was approved by the Institutional Review Board of Wonkwang University Hospital (IRB ID No. WKUH 2020-03-021) and was designed as a population-based cross-sectional study.

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As TN is an unusual chronic pain due to its episodic, variable, and unpredictable nature, its prevalence is relatively rarer than other neurogenic disorders. Up to now some retrospective studies have reported the epidemiology, incidence, and prevalence of TN, but most of them focused on a restricted area [10] or Western countries [13-15]. A study in the US reported that the annual incidence of TN was 5.9 per 100,000 person-years in female and 3.4 per 100,000 person-years in male. The incidence increased with age, and female’s incidence was slightly higher in all ages [14]. A retrospective cohort study in United Kingdom primary care reported the incidence of TN as 26.8 per 100,000 person-years [15]. A community-based study in Germany reported a lifetime prevalence of 0.3%, and in Netherlands the incidence rate of TN was 21.7 per 100,000 person-years [11,16]. These studies were mostly based on limited populations centered on local hospitals. However, our study was the first national wide study using electronic population data with a larger study group, differentiating it from other studies. In the present study, the prevalence of TN was 100.25 per 100,000 person-years in 2018, with the highest prevalence rate in both sexes in the age group of 51-59 years. The male to female ratio in the prevalence of TN was previously reported as being 1:1.9 [17] or 1:2.0 [18]. In the present study with larger study population, the ratio was 1:2.14. The differences in pain perception between the sexes have, as of yet, been poorly understood. In the previous study, the ways the brain responds to the pain were suggested as having sex differences in the pain stimulation [19]. In addition, there is a report on the existence of a significant association with gene polymorphism affecting serotonin release in the group of female suffering from TN [20].

In Korea, one study previously mentioned that the prevalence of TN was 81.8 per 100,000 person-years [21]. However, there was no consideration of the various epidemiological characteristics of TN in that study. In the present study, we used the most up-to-date data available data between 2014 and 2018 in Korea, with other various parameters such as regional distribution, medical cost, healthcare resource utilization, and prescription patterns by medical specialty. In view of the regional distribution, TN was more prevalent in the metropolitan areas, such as Seoul and Gyeonggi. Regarding the medical resource utilization, PHCFs were most commonly visited, followed by hospitals and general hospitals. Nobody knows the exact reason for the difference. This means that the primary physicians should have accurate knowledge of TN in the management of orofacial pain. Patients with TN were mostly managed by the department of neurology, followed by otorhinolaryngology, neurosurgery, anesthesia and pain medicine, and internal medicine. The medical cost for the treatment of TN in Korea has increased rapidly from 3,910,766 USD at the end of 2014 to 6,248,592 USD in 2018, with an increase of 159.77%. Interventional treatment is recommended in clinical practice for the management of cases that are refractory to conventional pharmacological treatment [22]. The medical costs were highest in the department of neurosurgery and anesthesia and pain medicine, where interventional treatments (nerve blocks or surgery) are the major modes of management, which differs from the other departments. For effective management of TN, guidelines on primary care and referral to specialists will be helpful. In addition, various recognized clinically effective interventional treatments should be known as other treatment options.

Management of TN should initially begin with a pharmacologic approach, in the form of monotherapy. In refractory cases, combination therapy, using different kinds of drugs, could be also used. Anticonvulsants, including carbamazepine and oxycarbazepine, have been known to be first line medications [23]. To the best of our knowledge, to date, there has been no study on the prescription patterns for the management of TN. Based on our results, the most commonly prescribed drug in Korea was an anticonvulsant drug, followed by NSAIDs and opioids. Anticonvulsants, such as carbamazepine and oxcarbazepine, are the drugs of choice for the pharmacologic management of TN [24]. They inhibit the function of voltage-sensitive sodium channels in hyperexcited neuronal membranes, thus raising the threshold of excitability inhibiting the high frequency repetitive neuronal firing characteristic of TN [25]. In contrast, there is no evidence to support the use of NSAIDs for the treatment of neuropathic pain [26]. Moreover, NSAIDs are not recommended for long-term administration to treat patients with neuropathic pain syndrome because of side effects such as adverse cardiovascular events [27]. Nevertheless, our study found that NSAIDs were the second most prescribed drugs for TN. More research on the risks and benefits of NSAIDs in drug treatment of TN may be needed. Opioids can reduce pain during short-term use for the management of chronic neuropathic pain; however, the review of clinical evidence found insufficient evidence to determine whether pain relief continues and long-term opioid therapy improves function or quality of life [28]. Further, this study showed that the use of opioids as an adjunct to antiepileptic drugs is prevalent in patients with TN, despite the lack of evidence regarding the efficacy of neuropathic pain management and the risk of abuse, addiction, and diversion [29].

This study had some limitations. First, this study does not include personal data because they are based on HIRA. In other words, individual patients are not traceable, and the disease characteristics of individuals are unknown. The prevalence could have been undervalued or overstated because the number of patients was counted only by the diagnostic code. Second, although many patients with TN may initially visit a dentist and receive medication or surgical treatment, dental claims are not included in the database. And a detailed analysis on the medical cost related to the managements of TN was also not performed. Third, we only evaluated specific medications of interest; however, as these were selected based on expert clinical judgment, we were confident that they were generally representative of the treatments utilized by patients with TN. However, the reasons for medication switches, discontinuation, and treatment outcomes cannot be fully explained with observational studies, and future studies should explore alternative designs to address these questions.

In conclusion, this is the first epidemiological study of TN in Korea based on the electronic population data from HIRA. The results of this study will not only help to understand the characteristics of TN in Korea, but also serve as an important basis for patients to receive an accurate diagnosis and effective treatment with less cost. Based on our study results, further study, focused on the individual characteristics of TN with large population data, is needed, which would be useful for both patients and physicians.

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