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Demographic characteristics of epilepsy patients and antiepileptic drug utilization in adult patients: Results of a cross-sectional survey
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.193806
Background: Through this cross-sectional study, we examined the demographic parameters, comorbidities, and antiepileptic drug (AED) utilization in patients with epilepsy. Keywords: Epilepsy; India; management pattern
Epilepsy is the most common chronic neurologic disorder across the world with approximately1% of the population being affected by it.[1] Importantly, approximately 80% of the people suffering from epilepsy are from the developing world.[2] Epilepsy is ranked either as the first or the second most common neurological disease in India. In India, the reported annual incidence of epilepsy is around 40–50 per 100,000 per year.[3] Despite being such a common disease, there is a significant treatment gap, especially in the low income countries.[2],[4] Epilepsy care in the developing countries differs from that in the developed countries because of cultural and economic differences.[1] Secondly, with less number of neurologists in the country, many times, the patient may visit a primary care physician, who may not be well-equipped with sufficient knowledge about the types of epilepsies and their management.[1] It is important to understand the challenges in the diagnosis and treatment of epilepsy, and efforts should be made to reduce the treatment gap in epilepsy.[5] The data from epidemiological and surveillance studies provides information necessary for the early detection, primary prevention, setting up of public health policies, definition of health care priorities and treatment management plan, and in the identification of educational and service needs. With this background, this study was undertaken to understand the demographic profile, treatment modalities and comorbidities associated with patients suffering from epilepsy in India.
Study settings In this cross-sectional, observational, non-interventional, study, a total of 973 patients from 57 centers across all geographical regions (east, west, north, and south) of India were included over a recruitment period from December 2013 until October 2014. The centers were chosen to represent different geographical areas and different demographic populations of India. Study subjects In this study, patients aged 18 to 65 years with either localization related epilepsy (LRE), focal seizures, or generalized seizure/idiopathic generalized epilepsy (IGE), epileptic spasms (ES), juvenile myoclonic epilepsy, Lennox–Gastaut Syndrome (LGS), and mesial temporal lobe epilepsy syndrome (MTLES) were enrolled. Patients with a history of nonepileptic seizures (e.g., metabolic, pseudoseizures, etc.), or those with seizures related to drugs, alcohol, acute medical illness, mental retardation, or situation-related seizures, progressive encephalopathy or findings consistent with progressive central nervous system (CNS) disease or lesion (e.g., infection, demyelination or tumor) were not included. Patients whose clinical and laboratory data did not allow a clear determination of whether or not the patient had epilepsy; or, in whom the diagnosis of LRE, IGE, ES, LGS, or MTLES was suspect, were not included in the study. In addition, patients having a history of pancreatitis, nephrolithiasis, or hypercalciuria, or clinically significant laboratory abnormalities suggestive of metabolic imbalance, and pregnant or lactating women, were not included in the study. Study instruments Healthcare professionals filled information in a web-based case report form. The information collected was based on a questionnaire in English language, containing items on demographic details such as the age and gender of the patient, state of residence, education, occupation, history, type and duration of epilepsy, seizure control and frequency, seizure freedom (seizure-free period in months) with current therapy, current treatment and treatment history, and medical history. The demographic details, presence of significant medical history (especially pertaining to comorbid conditions), or any significant past medical history and current treatment were recorded. The safety was evaluated by recording adverse events (if any). Due to the cross-sectional study design, no new treatment or intervention was administered. Sample size calculation and sampling Based on the World Health Organization recommendation [6] of including a minimum of 600 samples for a cross-sectional survey to investigate the use of medications in health facilities, we selected the sample size. Convenience samples of consecutive patients were used in the study. Statistical analysis All the enrolled patients were considered for analysis. Number and percentage of seizure-free patients was calculated. Data with continuous variables were summarized using mean, standard deviation, and range; whereas, categorical variables were summarized using frequency and percentage. Ethics approvals After approval of the protocol by Ethics Committee, the study was conducted in compliance with the protocol and ethical principles laid down by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use–Good Clinical Practice (ICH-GCP) guidelines that have their origins in the Declaration of Helsinki, Indian regulatory and guidelines [Indian Council of Medical Research (ICMR) and Indian GCP guidelines), and Indian GCP guidelines. Eligible patients were included after obtaining a written consent.
Characteristics of the study participants We recruited 973 patients with epilepsy from the entire country. The respective contribution of patients from various states was as follows: Telangana 214 (22.0%), Maharashtra 119 (12.2%), Kerala 61 (6.3%), Karanataka 56 (5.8%), Jammu and Kashmir 37 (3.8%), Andhra Pradesh 37 (3.8%), Tamil Nadu 35 (3.6%), Delhi 28 (2.9%), Uttar Pradesh 26 (2.7%), Punjab 20 (2.1%), Haryana 19 (2.0%), Gujarat 18 (1.8%), Rajasthan 3 (0.3%), Uttarakhand 2 (0.2%), Assam 1 (0.1%), and Arunachal Pradesh 1 (0.1%). Data on the place of residence were missing in 296 (30.4%) subjects. The mean age of the study population was 35.6 + 12.6 years. The study population consisted of 61.3% male and 38.7% female patients. The other demographic details and clinical characteristics are presented in [Table 1].
A total of 69.4% patients were either graduates or postgraduates [Table 1] whereas 54.7% patients were unemployed. Only 1.2% patients with epilepsy had a history of brain injury. Epilepsy types and subtypes The overall number and percentages of patients with generalized seizures, partial seizures, and unclassified seizures were 719 (81.1%), 149 (16.8%), and 19 (2.1%), respectively. The corresponding number and percentage in female patients were 282 (82.2%), 47 (13.7%), and 14 (4.1%); whereas, in male patients, the figures were 437 (80.3%), 102 (18.8%), and 5 (0.9%), respectively. The subtypes of partial and generalized seizure in the overall population are shown in [Table 2].
Among the patients with a history of brain injury, tonic–clonic seizures were present in 25% of the patients [Table 3]. The mean frequency of seizures during the previous 6 months was 24.0 ± 49.1 whereas, the mean duration of epilepsy was 5.8 ± 5.8 years. Electroencephalography was the most common (59.7%) investigation modality in patients with epilepsy followed by magnetic resonance imaging [MRI] (33.4%), computed tomography (CT) scan (28.3%), and other neuroradiological investigations (0.82%). A total of 109 (11.2%) patients had a relevant medical or surgical history whereas 95 (9.8%) patients were receiving concomitant medications. Hypertension was seen in 3.3% of the patients with a concomitant medical illness whereas diabetes mellitus was found in 2.4% patients [Figure 1].
A total of 956 (98.3%) patients were receiving treatment for epilepsy with antiepileptic drugs (AEDs). Levetiracetam was used in 583 (59.9%) patients whereas valproate, clobazam, and phenytoin were used in 16.3%, 14.8%, and 13.6% patients, respectively. The use of other AEDs is shown in [Table 4]. Levetiracetam was used in 34.9%, 45.7%, and 61.1% patients and valproate in 15.2%, 10.9%, and 4.6% patients in the age group of 18–30, 31–50, and 51–75 years, respectively. The epilepsy control with respective AEDs in the specific epilepsy type is shown in [Table 5]. Levetiracetam was used in 57.7% and 63.4% male and female patients respectively, whereas the corresponding percentages for valproate usage was 19% and 12.2%, respectively [Table 6].
The two most important reasons for selecting an antiepileptic agent were the effectiveness and safety/tolerability profile of the medicine. Effectiveness followed by safety and tolerability were the main criteria for selecting one medicine over the other, according to 39.6% and 26.7% participants, respectively [Figure 2].
A total of 924 (95.00%) had seizure control with the current therapy during the previous 6 months. The control achieved according to the epilepsy type with the current therapy during previous 6 months is shown in [Figure 3]. The mean seizure-free interval with the current therapy was 7.1 ± 4.1 months. All the patients in the study tolerated medications very well. The reported adverse event rate was only 0.1%.
Epilepsy is one of the most common problems in neurology clinical practice. However, there are not many studies showing the drug utilization pattern and other epidemiological profiles of the patients. Few studies have reported findings from an individual tertiary care centre.[7],[8],[9],[10],[11] Studies conducted by Mistry et al.,[7] and Bhatt et al.,[8] are in the pediatric population where as Silet al.,[9] reported the findings on antiepileptic drug utilization in epilepsy due to neurocysticercosis. According to the best of our knowledge, there is no multicentric study from India that has examined the drug utilization pattern in epilepsy. In this nationwide study, we analyzed the demographic profile and treatment modalities and co-morbidities in patients with epilepsy in India. Out of 973 patients, in this study, 61.3% were male patients. This finding is in accordance with a study that analyzed AEDs prescription and utilization behavior from a reputed national hospital of India with 67.9% male patients.[11] Epilepsy is associated with multiple challenges including a high unemployment rate [12] and lower intelligence.[13] In our study, 69.3% patients were either graduates or postgraduates, but only 45.3% were employed, indicating that epilepsy affects the employment status of a person. Traumatic brain injury is an important cause of epilepsy;[14],[15] however, in our study, only 1.2% patients had a history of brain injury. Patients with epilepsy often have other medical illnesses, of which hypertension and diabetes are commonly observed comorbidities in these patients.[16] In our study population, 11.2% had comorbidities. The most common medical illnesses in patients with epilepsy included hypertension and diabetes. The most important and first step in selecting an antiepileptic medicine is the proper identification and classification of seizure type and epilepsy syndrome in the patient.[17] Martin Brodie, in 1999, cited that because dosing is not very high, cost should not be a major factor while selecting an antiepileptic agent for patients with newly diagnosed epilepsy in the developed world.[18] This seems to be true in real life practice in India, even though cost is often considered as a barrier for the use of medicines in developing countries; in this study, 'effectiveness of the anticonvulsant medication' was considered as the main criteria by approximately 40% of the participants. This is possibly because an effective long-term control of seizure might indirectly save the cost of the medication over the long term. A single center study from Hyderabad reported clobazam and phenytoin as the most commonly used AEDs in febrile convulsions and in idiopathic generalized epilepsy, respectively.[10] Most of the patients in our study were on AEDs. Our findings are different from those reported by Mathur et al.[10] Even in generalized epilepsy, we observed more usage of levetiracetam. Overall, levetiracetam was most the commonly used AED in generalized epilepsy in our study. Consistent with the finding from another study,[11] we observed an increasing trend toward the usage of newer AEDs, with levetiracetam being used more commonly compared to the older AEDs such as valproate and phenytoin. Levetiracetam is a well-established second-generation AED with minimal metabolism, no CYP450 isoenzyme-inducing potential and clinically insignificant drug interactions. Levetiracetam does not cause weight gain.[19] Special populations, such as elderly patients, require different considerations while selecting an AED compared to the general adult population because of the commonly associated adverse drug effects.[20] In elderly patients with liver diseases, drugs not metabolized in the liver are preferred. Similarly, the potential of drug interactions with other concomitantly administered medications also becomes an important criteria for selection of an AED for an elderly person.[21] Carbamazepine and phenytoin are hepatic enzyme-inducing AEDs whereas valproic acid is an enzyme inhibitor.[22] In this regard, levetiracetam is a suitable AED.[21] Levetiracetam has a favourable safety profile for use in the elderly and in patients with liver dysfunction.[23] In our study, levetiracetam was used more commonly than other AEDs in all three (18–30, 31–50, and 51–75 years) studied age groups. We did not include children, which is one of the limitations of our study. In the pediatric population, the most commonly prescribed drug is sodium valproate, according to a single center study conducted by Bhatt et al.[9] Another study in children reported the treatment of focal seizures mainly with carbamazepine.[8] 'Women of childbearing age' constitutes another group that requires special consideration as women with epilepsy have more reproductive and endocrinal problems compared to the general female population.[22] Similarly, other factors such as interactions with hormonal contraceptive medications,[24] the teratogenic effects of drugs, the language, and motor development problems in children with an in utero exposure to AEDs [25] also makes selection of AED more challenging. With these considerations, changing trends in the use of AED in women of childbearing age have been seen over the last few years.[26] Levetiracetam exposure in utero is found to be superior in terms of language and motor development of children compared to valproate.[25] In our study, levetiracetam was used more commonly that other AEDs in female patients. Strengths and limitations The major strength of this study was to be able to recruit a large number of patients with epilepsy. We feel that these findings possibly reflect a real life presentation and treatment pattern of epilepsy in India. The study has some limitations. Convenience sampling was the limitation of the present study. Being a cross-sectional study without follow-up, there is a chance that adverse events are under-reported. This study does not give insights into drug utilization in children with epilepsy. There were also no objective parameters to evaluate the efficacy and safety of the antiepileptic agents; hence, the findings regarding safety and efficacy should be interpreted carefully. In some of the categories, sample size was very small, and hence, the percentages might not be the true representations of the evaluated parameters. Nonetheless, the study provides a good insight regarding the demographic parameters, comorbidities, and antiepileptic drug utilization pattern in adult patients with epilepsy in India.
Epilepsy is a common neurological problem in Indian patients. Hypertension and diabetes are two most common comorbidities in patients suffering from epilepsy. Efficacy and safety are considered more often than cost while selecting an anti-epileptic drug (AED). Levetiracetam is the most commonly used AED across all the studied age groups and in both genders. Control of epilepsy with AED is satisfactory with no major adverse events reported in this cross-sectional study. Acknowledgement Authors of this study wish to acknowledge the contribution of Dr. Anant D Patil in writing the manuscript. Financial support and sponsorship Both authors are employees of Abbott Healthcare Pvt Ltd. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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