Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked, seizures caused by sudden, excessive electrical discharges in brain cells. Symptoms range from blank staring and temporary confusion to uncontrollable jerking (convulsions) and loss of consciousness. While often caused by brain injuries, strokes, tumors, or genetic factors—or sometimes unknown causes—it is managed with medication, surgery, or diet, allowing many to live active lives. The objective of the DUR is to promote rational drug consumption among populations. For individual patients, rational drug utilization refers to the prescription of a comprehensive documented medication in an appropriate dosage for an accurate indication, with the correct information, and at a reasonable cost. In the absence of facts regarding the endorsement and utilization of drugs, initiating a conversation on rational drug usage and suggesting strategies to enhance the inclination to promote drugs to executives becomes challenging. The historical performance of prescribers is crucial for any evaluation system.Drug utilization studies serve as robust investigative instruments for determining the societal impact of medications. They establish a robust socio-medical and health-economic foundation for making decisions on healthcare. It is a highly efficient approach for evaluating the prescribing behavior of doctors^2-3. Drug utilization studies are crucial in guiding sensible drug prescription practices, thereby reducing the likelihood of side effects and enhancing patient adherence and overall quality of life⁴. Epilepsy, the second most common neurological condition after headache, is characterized by recurrent seizures of cerebral origin. Fifty million people in the world and an estimated 6 to 10 million people in India suffer from epilepsy.^5-7 It is of concern that the diagnosis and management of epilepsy is often suboptimal in developing countries and in the European region .However, in underdeveloped countries, the prevalence has been shown to exceed 40 cases per 1000 individuals⁸. Furthermore, the prevalence of epilepsy within the population exhibits heterogeneity across different age cohorts⁹. Neurologists frequently encounter epilepsy as the second most prevalent chronic neurological disorder. The estimated number of individuals with epilepsy in India is 550,000¹⁰. There are three fundamental mechanisms of action that are shared throughout the five available antiepileptic medications (AEDs). The effects of these substances include the reduction of repeated firing caused by interference with sodium currents, the enhancement of β-amino butyric acid (GABA) neurotransmission, or the reduction of transient Ca++ currents¹¹. Population-based studies have revealed that a significant proportion, ranging from 19-24%, of individuals diagnosed with epilepsy employ poly-therapy in conjunction with AEDs¹². Research on individuals with refractory epilepsy, including children and adults, revealed that 64% of participants employed poly-therapy by using two or more AEDs. Additionally, 35% of the adults experienced comorbid disorders connected to the central nervous system, which significantly increased the likelihood of interactions¹³. Inadequate patient compliance with pharmaceutical regimens is a prevalent factor contributing to heightened rates of death. The annual direct expenses incurred by the U.S. health care system due to non-compliance have been estimated to range from $100 billion to $289 billion. Numerous researches have been conducted to investigate the present state of medication adherence, its determinants, its correlation with patient outcomes, and strategies for enhancing it. Hence, the identification of precise and uniform metrics for assessing medication adherence holds significant significance¹⁴. It is imperative to conduct a thorough assessment of the potential risks and benefits associated with the prescription of antiepileptic medication, as well as engage in a comprehensive conversation with the patient regarding the advantages and potential adverse effects of the treatment. The majority of individuals with epilepsy will achieve seizure-free status by the administration of suitable antiepileptic drug (AED) therapy, after which they will undergo evaluation by primary care providers¹⁵. Conducting a study on drug utilization patterns of antiepileptic drugs at a tertiary care hospital in India is essential for several reasons. It facilitates the evaluation of prescribing methodologies, patient characteristics, and treatment results pertaining to antiepileptic medications, so aiding healthcare professionals in enhancing therapeutic approaches, reducing unfavorable occurrences, and enhancing patient well-being.

AIMS AND OBJECTIVE

• To evaluate the prescribing trends of anti-epileptic drugs (AEDs) in patients with epilepsy in a tertiary care hospital.

Study design: Hospital based cross-sectional, observational study. Study duration: 12 months . Study place: Dept. of Pharmacology in association with the Department of Neurology, S.P.Medical College and P.B.M Hospital, Bikaner Study population: Epilepsy patients attending the Neurology OPD and Medicine IPD within the study period were recruited in the study after taking written informed consent. Sample size:. A random sample of 200 patients who met the inclusion criteria was recruited. Sampling Method: Random sampling Inclusion Criteria: All patients with seizures of either sex , age >18 years who are prescribed anti-epileptic drugs were included in the study. Willing to participate in the study Exclusion Criteria: Patients who were unable to co-operate. Patients with inability to give consent. Patients treated with traditional medicines alone. Drug over-dose (deliberate or unintentional). Cases of relapse due to non-compliance. Patients with status epilepticus and seizures associated with acute conditions like stroke or other illnesses like hypertension, diabetes, chronic pulmonary obstructive disease, etc. Data Collection: After reading the basic demographic profile, following information will be collect from them (patients or their guardians); duration of illness, number of previous hospitalizations, type of epilepsy, severity of illness, current anti-epileptic treatment, number of drugs, drugs names, dose at the time of the visit, duration of present treatment and the reason for initiating current treatment (first episode, drug substitution

The mean age of patients was 33.67±11.33 Yrs. 117 patients were male .148 patients were married. 178 patients were literate. 58 patients were doing private jobs, 57 patients were house wives, 51 patients were doing government jobs and 37 patients were illiterate.

Most frequently prescribed drugs as monotherapy were phenytoin (33.00%), valproate (29.50%) and carbamazepine (18.00%).The other drugs prescribed to the study population included clobazam (4.00%), oxcarbazepine (4.00%), phenobarbitone (1.00%), topiramate (1.50%) and gabapentin (1.50%).  The drugs prescribed in combinations to the study population included phenytoin plus lamotrigine (3.5%), carbamazepine plus leviteracetam (2.00%) and phenytoin plus gabapentin(2.00%). Most common adverse drug reaction was drowsiness (63.50%), headache (52.50%), headache (52.50%), blurred vision (15.50%), dizziness(10.50%), slurred speech (7.50%),fatigue(6.50%) and  vertigo (4.50%).

Most common adverse drug reaction was drowsiness (63.50%), headache (52.50%) , blurred vision (15.50%), dizziness(10.50%), slurred speech (7.50%),fatigue(6.50%) and  vertigo (4.50%). These results of adverse effects are reflective of multiple adverse effects present in individual study subjects

The pie chart below represents an isolated adverse effect amongst the studied  individuals.

Epilepsy has a considerate impact in the quality of life with extensive and life long consequences. In the present study the mean age of the patients were 33.67+-11.33 years. Out of 200 patients 117 were male and 83 patients were females.

Similar to our result, a study conducted by sonali A et al16 on patients of epilepsy (irrespective of the type of epilepsy) showed that out of 60 patients , 35 were men and 25 were women. The mean age of respondents was 30.17 years. The range of seizure frequency in the past 1 year was 1-4 with a mean of 2.367 and mean duration of epilepsy was 6.9 years.

Ahangar JA et al17 in his study found that the mean age of the study population was 36.6years and 64.9% of them were males and the rest 35.1% of them were females.

Anne M Nabukenya et al18 found that 50% of the patients were aged below 25 years; 51% had attained primary school education level at most and the majority of the patients (77%) were never married. The average age was 26.6 years(SD =11.1).

Norsa’adah B et al19 found that the mean age was 31.8 years old( standard deviation 11.0) and 56.6% were females.

In the present study most frequently prescribed drugs to the study population were phenytoin (33.0%), valproate (29.50%) and carbamazepine (18%). The other drugs prescribed to the study population include clobazam (4.0%), oxcarbazepine (4.0%), phenobarbitone (1.0%), topiramate (1.5%) and gabapentin (1.5%).

It was observed that tonic clonic seizures had the highest prevalence rate at 20.1%, followed by complex partial seizures at 18.1% and simple partial seizures at 14.5%. Myoclonic seizures (13.7%), atonic seizures (13.3%), and absence seizures (12.9%) exhibit lower prevalence rates, with tonic seizures being the least frequent (7.6%). The presented data illustrates a wide array of seizure types, with tonic clonic seizures being the most prevalent.

The findings presented in this study align with previous research conducted by Akinsulore et al20and Murthy et al21 who similarly identified tonic clonic seizures as a prominent diagnostic category.

Our healthcare facility employed a limited selection of six unique antiepileptic drugs. The findings of the study indicate that VALPROATE emerged as the most frequently prescribed antiepileptic medicine. Tonic clonic seizure was the commonest diagnosis. The majority of the study population was under polytherapy for epilepsy management. A detailed analysis indicated a relatively lower frequency of prescriptions for medications like midazolam and levetiracetam.

The findings of our current study indicate that a significant proportion (62.4%) of the study group is undergoing multiple medication therapy, whilst 37.6% are receiving monotherapy. These findings indicate that combination therapy is more frequently employed compared to monodrug treatment. Additionally, a separate study revealed that 35.83% of the participants were receiving monotherapy, while 64.16% were undergoing multi-drug therapy, which involved the use of two or more antiepileptic medications.

Monotherapy is favored in epilepsy management for its reduced risk of adverse reactions and drug interactions. It simplifies treatment, improves adherence, and allows for better assessment of medication effectiveness, ultimately enhancing seizure control and patient quality of life22.

Since the 1990s, second-generation AEDs like lamotrigine and levetiracetam have been common, with new third-generation AEDs such as lacosamide recently introduced. These newer AEDs have better safety profiles and fewer side effects. Monotherapy with these AEDs is often preferred due to their effectiveness and improved tolerability23.

Since the early 1980s, polytherapy has been used for refractory epilepsy to achieve synergistic effects or reduce toxicity by combining smaller doses of multiple drugs instead of higher doses of a single medication24. Further trials resulted in a modification of this approach by confirming monotherapy as the primary treatment modality25. In the case of these individuals, polytherapy is not only deemed appropriate, but also considered normative treatment26.

In a study conducted by Deckers et al.27, compared that CBZ and VPA combination therapy had better outcomes than CBZ monotherapy, though not statistically significant, and faced criticism for pharmacokinetic interactions without proven synergy.

A trial by Kwan and Brodieet al28 found that after two failed monotherapy attempts, combination therapy showed better seizure control in drug-resistant epilepsy.A 20-year follow-up study showed that while monotherapy maintained a steady 60% seizure freedom rate, polytherapy nearly tripled its effectiveness, with seizure freedom increasing from 3% to 8.4%29.

The present survey revealed that PHENYTOIN was the most often given antiepileptic medication. Currently, there are more than 20 antiepileptic medicines that are readily accessible for therapeutic application. Our hospital utilized only six distinct antiepileptic medications.

A study conducted in India by Thomas SV et al (2001)30 found that Carbamazepine was the most prescribed medication, while other studies show sodium valproate as the most common, followed by phenytoin31.                                                         

In 1966, Meunier and colleagues conducted the first human trial of valproic acid (VPA) showed it significantly reduced seizures with minimal side effects in 12 patients with refractory epilepsy. By 1978, the FDA approved VPA for treating absence seizures32.           

Our tertiary healthcare facility had a limited selection of antiepileptic drugs. The findings of my study indicate that phenytoin emerged as the most frequently prescribed antiepileptic drug followed by sodium valproate and carbamazepine. Tonic clonic seizure was the commonest diagnosis. The majority of the study population was under monotherapy for epilepsy management. The study also indicated a relatively lower frequency of prescriptions for medications like lamotrigine , topiramate and levetiracetam. The most common adverse drug reaction was drowsiness followed by headache.

1.Sutharson L, Hariharan RS, Vamsadhara C. Drug utilization study in diabetology outpatient setting of a tertiary hospital. Indian J Pharmacol 2003; 35:237.

2. Baksaas I, Lunde PK. National drug policies: The need for drug utilization studies. Trends Pharmacol Sci 1986; 7:331-4.
3. Yuen YH, Chang S, Chong CK, Lee SC, Critchley JA, Chan JC. Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs. J Clin Pharm Ther 1998; 23:287-94.                             
4. Huwer C. Are colloid solutions essential for the treatment of pediatric trauma or burn patients. Review for the Expert Committee on the Selection and Use of Essential Medicines, Violence and Injury Prevention and Disability, Geneva, Switzerland, 2012.
5. World Health Organization. Epilepsy: Epidemiology, Aetiology and Prognosis. WHO Factsheet. 2001. Available from http://www.who.int/ mediacentre/factsheets/fs165/en/. [Accessed October 1, 2014].
6. Banerjee PN, Filippi D, Allen HW. The descriptive epidemiology of epilepsy—a review. Epilepsy Res 2009;85:31–45.
7. Gourie-Devi M, Satishchandra P, Gururaj G. Epilepsy control program in India: a district model. Epilepsia 2003;44(Suppl. 1):58–62.
8. Hauser WA. Recent developments in the epidemiology of epilepsy. Acta Neurologica Scandinavica. 1995; 162 (suppl.): 17- 21.
9. Sander JW, Hart YM, Johnson AL, Shorvon SD. () National general practice study of epilepsy: newly diagnosed epileptic seizures in a general population. Lancet. 1990; 336: 1267-1271.
10. Sridharan R. Epidemiology of epilepsy. Current Science. 2002; 82: 664-670.
11. Heinemann U, Draguhn A and Ficker E. Strategies for the development of drugs for pharmacoresistant epilepsies. Epilepsia. 1994; 35(5): 10-21
12. Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010;8(3):254-67.
13. Sunwoo JS, Jo H, Kang KW, Kim KT, Kim D, Kim DW, Kim MJ, Kim S, Kim W, Moon HJ, Park HR, Byun JI, Seo JG, Lim SC, Chu MK, Han SH, Hwang KJ, Seo DW. Survey on Antiepileptic Drug Therapy in Patients with Drug Resistant Epilepsy. J Epilepsy Res. 2021;11(1):72-82.
14. Zhao BMS, Eric C, Wong MS and Palaniappan L. Estimating patient adherence to medication with electronic health records data and pharmacy claims combined. Sas Global Formula 2013: 1-7.
15. Chadwick D and Reynolds EH. When do epileptic patients need treatment starting and stopping medication. Br Med J (Clin Res Ed). 1985; 290: 1885-88.

16 .Sonali A Pimpalkhute, chaitali S Bajait, Ganesh N dakhale. Assessment of quality of life in epilepsy patients receiving anti epileptic drugs in a tertiary care teaching hospital. Indian journal of pharmacology 2015;47(4):551-554.

17.Ahangar JA, Farhat S, Wani RT. Assessment of quality of life in patients on antiepileptic drugs: a hospital based cross sectional study. Int J Basic Clin Pharmacol 2019;8

18.Anne M Nabukenya. Health related quality of life in epilepsy patients receiving antiepileptic drugs at national referral hospitals in Uganda : a cross sectional study. Health Qual life outcomes 2014;12:49

19.Norsa’adah B, Zainab J, Knight A. The quality of life of people with epilepsy at a tertiary referral centre in Malaysia. Health and quality of life outcomes. 2013;11(1):143

20. Akinsulore A and Adewuya A. Psychosocial aspects of epilepsy in Nigeria. African J of Psychiatry 2010; 13: 351-56
21. Murthy VN, Anusha B and Perumal P. A Study on trends in prescribing pattern of antiepileptic drugs in tertiary care teaching hospital. Int J of Chemical & Pharma Sci 2012; 3(2): 25-32.
22. Nevitt SJ, Sudell M, Cividini S, Marson AG, Tudur Smith C. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2022 Apr 1;4(4):CD011412.
23. Reynolds, E.H., Shorvon, S.D. (1981) Monotherapy or polytherapy for epilepsy? Epilepsia, 22, 1-10.
24. Shorvon, S.D.; Chadwick, D.; Galbraith, A.W.; Reynolds, E.H. One drug for epilepsy. Br. Med. J. 1978, 1, 474–476.
25. Kwan, P.; Brodie, M.J. Early identification of refractory epilepsy. N. Engl. J. Med. 2000, 342, 314–319.
26. Kwan, P.; Brodie, M.J. Combination therapy in epilepsy: when and what to use. Drugs 2006, 66, 1817–1829.
27. Deckers CL, Hekster YA, Keyser A, van Lier HJ, Meinardi H, Renier WO. Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia 2001;42:1387-94.

28.Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314-9.

29. Brodie MJ, Barry SJE, Bamagous G, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012;78:1548-54.
30. Thomas SV, Sarma PS, Alexander M. et al. Economic burden of epilepsy in India. Epilepsia 2001; 42: 1052-60.
31. Malerba A, Ciampa C, De Fazio S, Fattore C, Frassine B, La Neve A, et al. Patterns of prescription of antiepileptic drugs in patients with refractory epilepsy at tertiary referral centres in Italy. Epilepsy Res. 2010 Oct;91(2-3):273-82.
32. Koch-Weser J, Browne TR. Drug therapy: Valproic acid. N Engl J Med. 1980;302(12):661-6.