|Year : 2012 | Volume
| Issue : 4 | Page : 289-293
Antiepileptic drugs prescription utilization behavior and direct costs of treatment in a national hospital of India
Ahsan Haroon1, Manjari Tripathi2, R Khanam1, Divya Vohora1
1 Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India
2 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||13-Mar-2012|
|Date of Decision||12-Apr-2012|
|Date of Acceptance||10-Jun-2012|
|Date of Web Publication||5-Dec-2012|
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062
| Abstract|| |
Background and Objectives: The present study evaluated the direct costs of active epilepsy and looked at the pattern of drug prescription and utilization in epileptic patients visiting the neuroscience centre of a national hospital of India. Materials and Methods: A total of 134 epileptic patients were studied over a period of 4 months. Patients demography, commonly prescribed antiepileptic drugs (AEDs), socioeconomic status, direct costs, response ratio (RR) for newer drugs, and quality of life (QOLIE-10) was evaluated. Results and Discussion: We found a higher percentage of male patients (67.9%) as compared with females. Most of the patients were in the age group 11-30 years and majority of them (39.6%) belonged to lower middle group. A higher percentage (68.7) of drugs was prescribed as polytherapy. Higher monthly cost was observed for some of the newer AEDs including the lamotrigine, levetiracetam, and lacosamide as compared with older drugs. Among the newer drugs, clobazam had the lowest cost. RR was calculated for 12 patients out of which 8 had a RR < −0.50. The QOL domains, following conventional or newer drugs, were not much affected. Conclusion: The study indicates an increasing trend toward clinical usage of newer AEDs, increasing trend of poly-therapy with significant escalations in the cost of therapy.
Keywords: Antiepileptic drugs, direct cost, prescription pattern, response ratio, quality of life
|How to cite this article:|
Haroon A, Tripathi M, Khanam R, Vohora D. Antiepileptic drugs prescription utilization behavior and direct costs of treatment in a national hospital of India. Ann Indian Acad Neurol 2012;15:289-93
|How to cite this URL:|
Haroon A, Tripathi M, Khanam R, Vohora D. Antiepileptic drugs prescription utilization behavior and direct costs of treatment in a national hospital of India. Ann Indian Acad Neurol [serial online] 2012 [cited 2014 Oct 30];15:289-93. Available from: http://www.annalsofian.org/text.asp?2012/15/4/289/104338
| Introduction|| |
Epilepsy is the second most common chronic neurological condition. It is estimated that there are 55,00,000 persons with epilepsy in India, that is, one-eighth of the total epilepsy patients in the world.  Though monotherapy is usually recommended in epilepsy but polytherapy is often required for patients with multiple seizure types or refractory disease.  Epilepsy can be treated effectively in approximately 60% of patients who become seizure free with the first or second antiepileptic drug (AED) that they are prescribed.  The drawback of polypharmacy is higher incidence of adverse effects, drug interactions and added costs. The latter constitutes an economical burden on the patients in addition to the existing psychological medical and social burden. 
Pharmacoeconomics is a branch of economics that measures and compares the cost, risks, and benefit of programs, services or therapies and determines which alternative produces the best health outcome for the resource invested. Outcome of Pharmacoeconomics are 'humanistic' and 'economic'.  Economic consequences are analyzed as direct or indirect costs and antiepileptic drugs are known to be contributing majority to the direct costs.  Humanistic evaluation is done by analyzing quality of life (QOL). 
Since there is a paucity of Indian studies who have examined the economic aspects of epileptic patients and the financial impact of newer AEDs prescription, the present study is designed to evaluate the direct costs of active epilepsy in patients visiting the neuroscience center of a reputed national hospital of India. In addition to this, the study also analyzed the pattern of drug prescription and utilization in different types of epilepsies. A better understanding of the economic aspects of epilepsy and utilization behavior would hopefully help identifying the most common cost effective treatment especially in patients with refractory epilepsy.
| Study Methods|| |
The study was carried out between January and April 2011 in the Neurosciences Centre OPD at All India Institute of Medical Sciences (AIIMS), New Delhi. The study aim was prospective analysis of AEDs prescription and utilization behavior as well as analysis of QOL data. For determining direct costs, the cost of investigations (eelectroencephalography (EEG), magnetic resonance imaging (MRI), and AEDs concentration in blood) were taken retrospective from 2010 to 2011. All patients diagnosed with epilepsy (irrespective of age and sex) were included in the study. Patients were classified according to gender, age, sex, seizure type, and socioeconomic status (SEC). For determining the SEC, Kuppuswamy's socioeconomic status scale was used.  Most commonly prescribed conventional and newer AEDs were determined. The direct costs (cost of AEDs + investigations), response ratio (RR), and QOL were also determined. RR was determined for patients prescribed with newer AEDs and was calculated by the difference between seizures at baseline (patient visited OPD last time) and after treatment (till 12 weeks) of add-on or per se therapy divided by the total number of seizures. A negative value for RR indicated reduction in seizures.  A value above −0.5 indicated at least 50% or more reduction in seizures. The patient's Quality of life was assessed by using a 10-item questionnaire QOLIE-10.  The QOLIE-10 covered general and epilepsy-specific domains and an overall quality of life. The statistical correlation between different domains of QOL was performed using Pearson correlation coefficient test. The results were analyzed using statistical program SPSS version 17, internal consistency measure (Cronbach's Alpha), item-item, and item total correlation measure.
| Results|| |
During 4 months study, 134 patients were observed to receive AED therapy at AIIMS. The demographic profile of patients, classification according to seizure type and SEC and the most commonly prescribed AEDs are depicted in [Table 1]. The AEDs were used as either monotherapy (31.34%) or polytherapy (68.66%).
The cost of MRI at AIIMS was divided into three types: MRI (Rs 3000), MRI with film (Rs 3500), MRI with contrast (Rs 7000). Out of 134 patients, 19 patients got free MRI from AIIMS and employees' state insurance (ESI) while 74 patients got free EEG from AIIMS and ESI. The consultant fee of OPD (AIIMS) was nominal (Rs 10). The direct cost to patient increased linearly by adding AED to prescription [Figure 1].
The baseline seizure period was taken from 1st January to 15th January for calculation of RR. Out of 134 prescriptions, only 12 were found to be on the newer AEDs having baseline seizures during that period. The seizures were considered to be controlled if there was 50% reduction in the RR. Of 12 patients, 8 patients had RR < −0.50 while 4 had RR > −0.50 [Table 2].
Quality of life
Out of 134 patients, 19 patients were less than 12 years of age while 9 patients did not respond personally/telephonic calls and were rejected for assessing QOL. The Cronbach's alpha was found to be 0.94. A reliability coefficient of 0.7 or higher is considered acceptable in most social sciences research situations. [Table 3] depicts the Pearson correlation coefficient for the various domains of QOLIE, which was correlated well (P < 0.001). The ratings of QOL were almost comparable for most AEDs on all the parameters of QOLIE-10. Comparing older drugs with newer AEDs did not reveal a significant difference.
|Table 3: Pearson correlation coefficients for the components of QOLIE-10 and quality of life scores of antiepileptic drugs|
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| Discussion|| |
There has been a recent interest to conduct drug utilization studies (DUS) involving economic aspects in epileptic patients. This is mainly due to an increased usage of newer AEDs that have escalated the costs of epilepsy treatment. In spite of a high economic burden of epilepsy in India,  not many studies have looked into the impact of newer AEDs on the cost of epilepsy treatment. The present study aims to look at this aspect on Indian epileptic patients.
About 134 epileptic patients were studied during a period of 4 months at the Neuroscience OPD of AIIMS, New Delhi. We found a higher percentage of male epileptics (67.9%) as compared with females (32.1%) [Table 1]. Similar observations (higher male:female ratio) have been reported in India  and Denmark  indicating that epilepsy is slightly more prevalent in the male gender. However, a 1:1 male:female ratio has been reported in Sri Lanka.  While the reasons behind gender differences are not clear, it has been generally observed that men have a higher incidence of focal epilepsy while women are influenced by genetic factors or hormones leading to a higher incidence of generalized epilepsy.  Maximum patients included in the study were between the age groups of 11-20 years (35.9%) followed by 21-30 years (27%). A higher percentage of patients were found to have generalized tonic-clonic seizures (GTCS) (45.5%) followed by focal seizure (33.6%). Absence and reflex seizures constituted only 1.5% of patients. In recent years, the number of drugs approved for epilepsy has been doubled. Newer AEDs provides clinicians with a wider choice to help patients achieve therapeutic efficacy even for those not responding to a conventional AED. The main reason for introducing a newer AED is the persistence in seizure activity.  We found that a higher percentage of patients prescribed more than one AED (68.7%) [Table 1]. A similar higher incidence of polytherapy (79%) has been reported in Italy with over one-third of patients being prescribed more than three AEDs.  The reasons for polytherapy could be due to an increase in prescription of second generation AEDs, most of which are approved only as add-ons. Our observations are in contrast to several other studies where a higher percentage of patients were prescribed monotherapy (70-96%) in India, , Sri Lanka,  and Nigeria.  The wide use of polytherapy is a concern particularly, since there is no evidence from randomized controlled studies that shows polytherapy is superior to monotherapy in achieving seizure control. ,
Valproic acid and/or sodium valproate was found to be the most commonly prescribed conventional AED (37.8%) followed by carbamazepine (31.1%), and phenytoin (20%) [Table 1]. Other studies have reported carbamazepine to be one of the most commonly prescribed drugs. , Although use of phenytoin has declined due to more side effects as compared with either carbamazepine or sodium valproate, we still found phenytoin use in 20% of prescriptions. This is because of higher efficacy of phenytoin in controlling epileptic seizures. In USA, phenytoin continuous to be the most commonly used AED (48%).  Among the newer AEDs, clobazam constituted 51% of prescriptions (even higher than carbamazepine) and was the most commonly prescribed drug. The second and third most commonly prescribed newer drugs were levetiracetam (21%) and lamotrigine (18%), respectively. A higher use of clobazam has been reported earlier both as montherapy and as an add-on.  The reason could be that it is a nonsedating, well tolerated benzodiazepine (BZD) with low cost and higher efficacy in most seizure types.  Unlike our study, clobazam was prescribed to only 14% of patients in Italy while levetiracetam was prescribed to 35% of patients.  Among the AED combinations, most frequently used combination was sodium valproate + clobazam followed by carbamazepine + clobazam. Other studies have reported levetiracetam as one of the components of combination  or carbamazepine + sodium valproate to be the most frequently used combination. 
The SES of the patients was determined with the help of Kuppuswamy's socioeconomic scale which is considered to be an important tool in hospital and community-based research in India.  It was revised in the year 2003 and it takes into consideration the education, occupation, and family income of the subjects. In our study, we found majority of patients (39.6%) belonged to lower middle group [Table 1]. This is a cause of concern, due to an increasing burden on patient for increasing cost of therapy. We compared the monthly costs of each AED prescribed and found a much higher cost for some of the newer AEDs including the lamotrigine (Rs 1009), levetiracetam (Rs 2305), and lacosamide (Rs 3885) as compared with the mean monthly costs of older drugs like carbamazepine (Rs 167), sodium valproate/valproic acid (Rs 366), or phenytoin (Rs 97). Among the newer drugs, clobazam, a BZD, had the lowest cost (Rs 227), one of the reason probably for the most commonly prescribed drug in our study where patients mainly belonged to the lower middle group.
The use of various diagnostic tests like EEG, CT scan, and MRI are also important predictors of total cost. In general, EEG is advocated to most patients. At this hospital, EEG was free of cost and the OPD consultation fee was nominal (Rs 10). The costs of MRI and blood tests, etc., contributed in addition to the cost of AEDs. [Figure 1] shows an increase in direct cost by increasing the number of AEDs in the prescription. A significant increase in cost, as observed from our study, suggests the need to encourage the use of cost effective AED to reduce economic burden of epilepsy. Polypharmacy and frequent use of newer AEDs, which are comparatively expensive than older AEDs like carbamazepine and sodium valproate, have escalated cost of epilepsy treatment in India. Less expensive drugs like phenobarbitone are seldom used now.
The efficacy/response of newer AEDs must be weighed against their costs. We calculated RR, to determine the efficacy of newer AED, wherever added, in the treatment regimen. In our study, RR was calculated for 12 patients as only these were found to have the baseline seizures at the initiation of therapy (January) and were prescribed add-on newer AEDs. A value above −0.5 indicated at least 50% or more reduction in seizures when observed after 12 weeks. We observed a RR > −0.5 in case of combinations: Levetiracetam + Zonisamide + Phenytoin + Lacosamide (−0.76), Valporic acid + Levetiracetam + Lamotrigine (−0.69), Levetiracetam + Clobazam + Sodium valproate (−0.64), and Levetiracetam + Zonisamide + Topiramate (−0.62) [Table 2]. Since the sample size is small, it is difficult to arrive at any conclusion regarding the efficacy of combinations. Nevertheless, > 50% reduction in seizures was observed in 4 out of 12 patients who were prescribed add-on newer AEDs.
QOL constitutes one of the humanistic aspects of pharmacoeconomics evaluations. We used QOLIE-10 which is a self-administered questionnaire designed for completion by patient alone. It comprises of 10 items. We recorded the answers either personally or telephonically after the end of 1 month. We also determined Cronbach's alpha, a marker of reliability to indicate how closely related a set of items as a group. Relative coefficient of 0.7 or higher is considered acceptable in most situations. We found a reliability coefficient of 0.94. Further, all domains of QOL correlated well with each other indicating that these domains were inter-linked. A close look at the QOL mean scores of 6 most commonly prescribed AEDs revealed a low score ranging from 1 to 3 for most of the domains of QOLIE-10 for both older and newer drugs. The energy level, fear of future seizure (anxiety) and other parameters indicating general well being of a person were almost comparable for both older and newer AEDs. The scores on driving ability were slightly worse as compared with other domains. There were no obvious differences even in the memory problem unlike various clinical reports indicating impairment of cognitive functions following AEDs.  Overall, QOL did not appear to be much affected (probably because of short duration of our study) and significant differences between older and newer AEDs were not discernible.
To conclude, our study indicates an increasing trend toward usage of newer AEDs in clinical practice, an increase poly-therapy (pointing toward a higher number of intractable cases) with significant escalations in the cost of therapy. The QOL domains following AED therapy, whether conventional or newer drug, were not much affected except driving ability. Thus, despite introduction of several new AEDs in the treatment armamentarium, a cost-effective therapy, especially for intractable cases where two or more drugs are required, is the need of the hour. However, our study was limited to one hospital with limited number of patients and was designed for limited duration of time. Shorter duration of current study (4 months) can interfere with the outcome of RR/QOLIE since seizure events outside this time frame may have effect on efficacy/QOL. There is definitely a need to conduct long-term multi-centric studies involving direct comparisons of cost with therapy response and QOL.
| References|| |
|1.||Sridharan R. Epidemiology of epilepsy. Curr Sci 2002; 82:664-70. |
|2.||Mathur S, Sen S, Ramesh L, M-Kumar S. Utilization pattern of antiepileptic drugs and their adverse effects in a teaching hospital. Asian J Pharm Clin Res 2010;3:55-9. |
|3.||Dhillon S, Sander JW. Epilepsy. In: Walker R, Whittlesia C.Clinical pharmacy and therapeutics. China: Churchill Livingstone; 2007. p. 447-60. |
|4.||Levy P. Economic evaluation of antiepileptic drug therapy: A methodological review. Epilepsia 2002;43:550-8. |
|5.||Townsend RJ, Ostechaus JT, Boyer JG. Pharmacoeconomics: Economic and humanistic outcomes. In: Fletcher AJ, Edwards LD, Fox AW, Stonier P, editors. Principles and practice of pharmaceutical medicine. Ch 19. Chichester, UK: John Wiley and Sons; 2002. |
|6.||Dhanaraj M, Kannan SR, Jayavelu A, Amalraj E, Dutta M. Cost of epilepsy treatment in a state government hospital: A preliminary study. Annals of Indian Academy of Neurology 2003; 6: 6-10. |
|7.||Hills MD. The psychological and social impact of epilepsy. Neurol Asia 2007;12:10-2. |
|8.||Mishra D, Singh HP. Kuppuswamy's socioeconomic status scale: A Revision. Indian J Pediatr 2003;70:273-4. |
|9.||Sethi A, Chandra D, Puri V, Mallika V. Gabapentin and Lamotrigine in Indian patients of partial epilepsy refractory to Carbamazepine. Neurol India 2002;50:359-63. |
|10.||Cramer JA, Perrine K, Devinsky O, Meador KA. Brief questionnaire to screen for quality of life in epilepsy: The QOLIE-10. Epilepsia 1996;37:577-82. |
|11.||Kuruvilla A. The burden and pharmacoeconomics of epilepsy in India. Epilepsia 1999;8:436-7. |
|12.||Sigamani A, Roy AK, Yeagani VK, Kulkarni C. Profile of Pharmacotherapy and Pharmacoeconomics of Epilepsy treatment at a Tertiary care hospital. Ann Neurosci 2006;13:1-16. |
|13.||Christensen J, Vestergaard M, Pederson MG, Pederson CB, Olsen J, Sidenius P. Incidence and prevalence of epilepsy in Denmark. Epilepsy Res 2007; 76: 60-65. |
|14.||Kariyaswami SH, Bandara N, Koralagama A, Senanayake S. Challenging epilepsy with antiepileptic pharmacotherapy in a tertiary teaching hospital in Sri Lanka. Neurol India 2004; 52:233-7. |
|15.||Malerba A, Ciampa C, Fazio SD, Flattore C, Frassine B, Neve AL, et al. Patterns of prescription of antiepileptic drugs in patients with refractory epilepsy at tertiary referral centers in Italy. Epilepsy Res 2010;91:273-82. |
|16.||Adikaibe-Ezela BA, Onwuekwe IO, Ekenze SO, Achor JU, Onwukwe JU. Estimated Direct cost of treating epilepsy per month in Southeast Nigeria. The Internet Journal of Neurology 2010;13:1-7. |
|17.||Banfi R, Borselli G, Marinai C, Borgheresi A, Cavalieri A. Epidemiological study of epilepsy by monitoring prescriptions of antiepileptic drugs. Pharm World Sci 1995;17:138-40. |
|18.||Pellock JM. Standard approach to antiepileptic drug treatment in the United States. Epilepsia 1994;35:11-8. |
|19.||Feely M. Drug treatment of epilepsy. Br Med J 1999;318:106-9. |
|20.||Perucca E. Current trends in antiepileptic drug therapy. Epilepsia 2003;44:41-7. |
|21.||Devi MG, Satishchandra P, Gururaj G. Epilepsy control program in India: A district model. Epilepsia 2003;44:58-62. |
|22.||Aldenkamp AP, Bodde N. Behaviour, cognition and epilepsy. Acta Neurol Scand Suppl 2005;182:19-25. |
[Table 1], [Table 2], [Table 3]
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