Background. Antiepileptic drugs (AEDs) noncompliance is associated with increased risk of seizures and morbidity in seizure disorder patients. Objective. To identify risk factors that correlated to higher levels of morbidity, measured by emergency room (ER) utilization by seizure disorder members taking AED. Methods. Patients with primary or secondary diagnosis of seizures, convulsions, and/or epilepsy and prescribed AEDs during an 11-month period were included in the study. Variables were analyzed using multivariate statistical analysis including logistic regression. Results. The study identified 201 members. No statistical significance (NS) between age, gender, number of tablets, type of drug, or other risk factors was associated with increased mortality. Statistical significance resulted with medication compliance review of 0–14 days, 15–60 days, and 61+ days between refills. 68% of patients with ER visit had noncompliance refill between 0 and 14 days compared to 52% of patients in non-ER group ( ). Contrastingly, 15% of ER group had refills within 15–60 days compared with 33% of non-ER group ( ). There was NS difference between two groups when noncompliance was greater than 60 days ( ). Conclusions. The study suggests that careful monitoring of pharmaceutical refill information could be used to identify AED noncompliance in epileptic patients. 1. Introduction Seizures are the most common pediatric neurological disorder. Of the roughly 150,000 children who experience a first-time seizure, it has been estimated that 30,000 will suffer from epilepsy [1, 2]. The terms seizure and convulsion are commonly used interchangeably, but for the purposes of this report we will simply use the term seizure [3]. Furthermore, the terminology of epilepsy and convulsive and/or seizure disorder used in this study is meant to be as inclusive as possible due to the fact that the accuracy of distinguishing an epilepsy diagnosis in the presence of seizures has been reported to range from 5% to 23% [4]. Regardless of the specific diagnosis, antiepileptic drug (AED) therapy is a hallmark therapeutic approach and the importance of adherence to AED regimes has largely been demonstrated to affect a patient’s risk of future seizures [5]. Several studies have explored various risk factors and their association with AED noncompliance. Clearly, it has been shown that AED noncompliance increases a patient’s risk for further seizure activity [5–9]. Furthermore poor seizure control has been linked to an increase in morbidity and mortality for patients [10, 11]. Several of these
References
[1]
M. J. Friedman and G. Q. Sharieff, “Seizures in children,” Pediatric Clinics of North America, vol. 53, no. 2, pp. 257–277, 2006.
[2]
S. Shinnar and J. M. Pellock, “Update on the epidemiology and prognosis of pediatric epilepsy,” Journal of Child Neurology, vol. 17, supplement 1, pp. S4–S17, 2002.
[3]
C. G. Goetz and E. J. Pappert, Textbook of Clinical Neurology, Saunders, Philadelphia, Pa, USA, 2nd edition, 2003.
[4]
C. A. Van Donselaar, H. Stroink, and W.-F. Arts, “How confident are we of the diagnosis of epilepsy?” Epilepsia, vol. 47, s1, pp. 9–13, 2006.
[5]
D. Buck, A. Jacoby, G. A. Baker, and D. W. Chadwick, “Factors influencing compliance with antiepileptic drug regimes,” Seizure, vol. 6, no. 2, pp. 87–93, 1997.
[6]
P. Loiseau and C. Marchal, “Determinants of compliance in epileptic patients,” Epilepsy Research. Supplement, vol. 1, pp. 135–140, 1988.
[7]
E. Santiago-Rodríguez, V. Sales-Carmona, and R. Ramos-Ramírez, “Risk factors for therapeutic non-compliance in patients with epilepsies,” Gaceta Medica de Mexico, vol. 138, no. 3, pp. 241–246, 2002.
[8]
S. S. R. Snodgrass, V. V. Vedanarayanan, C. C. Parker, and B. R. Parks, “Pediatric patients with undetectable anticonvulsant blood levels: comparison with compliant patients,” Journal of Child Neurology, vol. 16, no. 3, pp. 164–168, 2001.
[9]
I. Lusic, M. Titlic, and D. Eterovic, “Epileptic patient compliance with prescribed medical treatment,” Acta Medica Croatica, vol. 59, pp. 13–18, 2005.
[10]
M. R. Sperling, H. Feldman, J. Kinman, J. D. Liporace, and M. J. O'Connor, “Seizure control and mortality in epilepsy,” Annals of Neurology, vol. 46, pp. 45–50, 1999.
[11]
G. M. Peterson, S. McLean, and K. S. Millingen, “Determinants of patient compliance with anticonvulsant therapy,” Epilepsia, vol. 23, no. 6, pp. 607–613, 1982.
[12]
J. Wilby, A. Kainth, N. Hawkins et al., “Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation,” Health Technology Assessment, vol. 9, no. 15, 2005.
[13]
S. Nadkarni, J. LaJoie, and O. Devinsky, “Current treatments of epilepsy,” Neurology, vol. 64, no. 12, supplement 3, pp. S2–S11, 2005.
[14]
P. Camfield and C. Camfield, “Epileptic syndromes in childhood: clinical features, outcomes, and treatment,” Epilepsia, vol. 43, supplement 3, pp. 27–32, 2002.
[15]
J. A. French, A. M. Kanner, J. Bautista et al., “Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society,” Neurology, vol. 62, no. 8, pp. 1252–1260, 2004.
[16]
J. A. French, A. M. Kanner, J. Bautista et al., “Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the therapeutics and technology assessment subcommittee and quality standards subcommittee of the American Academy of Neurology and the American Epilepsy Society,” Neurology, vol. 62, no. 8, pp. 1261–1273, 2004.
[17]
S. M. Hadjiloizou and B. F. D. Bourgeois, “Antiepileptic drug treatment in children,” Expert Review of Neurotherapeutics, vol. 7, no. 2, pp. 179–193, 2007.
[18]
M. Goodwin, D. Wade, B. Luke, and P. Davies, “A survey of a novel epilepsy clinic,” Seizure, vol. 11, no. 8, pp. 519–522, 2002.
[19]
E. D. Marsh, A. R. Brooks-Kayal, and B. E. Porter, “Seizures and antiepileptic drugs: does exposure alter normal brain development?” Epilepsia, vol. 47, no. 12, pp. 1999–2010, 2006.
[20]
D. Polsky, J. Weiner, J. F. Bale Jr., S. Ashwal, and M. J. Painter, “Specialty care by child neurologists: a workforce analysis,” Neurology, vol. 64, no. 6, pp. 942–948, 2005.
[21]
F. Buchthal and O. Svensmark, “Aspects of the pharmacology of phenytoin (dilantin) and phenobarbital relevant to their dosage in the treatment of epilepsy,” Epilepsia, vol. 1, pp. 373–384, 1960.
[22]
F. Buchthal, O. Svensmark, and P. J. Schiller, “Clinical and electroencephalographic correlations with serum levels of diphenylhydanotin,” Archives of Neurology, vol. 2, pp. 624–630, 1960.
[23]
W. Froscher, G. Kramer, D. Schmidt, and H. Stefan, “Serum concentration of anticonvulsants: practical guidelines for measuring and useful interpretation. Therapy Committee of the German Section of the International Epilepsy League,” Nervenarzt, vol. 70, pp. 172–177, 1999.
[24]
W. Froscher, “Clinical relevance of the determination of antiepileptic drugs in serum,” Wiener Klinische Wochenschrift, Supplement, vol. 104, no. 191, pp. 15–18, 1992.
[25]
G. E. Schumacher and J. T. Barr, “Total Testing Process applied to therapeutic drug monitoring: impact on patients' outcomes and economics,” Clinical Chemistry, vol. 44, no. 2, pp. 370–374, 1998.
[26]
S. R. Snodgrass and B. R. Parks, “Anticonvulsant blood levels: historical review with a pediatric focus,” Journal of Child Neurology, vol. 15, no. 11, pp. 734–746, 2000.
[27]
C. F. Nhachi and G. M. Mwaluko, “Therapeutic drug monitoring (TDM): an aid to anti-epileptic drug (AED) therapy in Zimbabwe: a review,” East African Medical Journal, vol. 67, no. 5, pp. 311–318, 1990.
[28]
R. J. L. Walters, A. D. Hutchings, D. F. Smith, and P. E. M. Smith, “Inappropriate requests for serum anti-epileptic drug levels in hospital practice,” Monthly Journal of the Association of Physicians, vol. 97, no. 6, pp. 337–341, 2004.
[29]
R. G. Feldman and C. E. Pippenger, “The relation of anticonvulsant drug levels to complete seizure control,” Journal of Clinical Pharmacology, vol. 16, no. 1, pp. 51–59, 1976.
[30]
M. Da Mota Gomes, H. De Souza Maia Filho, and R. A. M. Noé, “Anti-epileptic drug intake adherence: the value of the blood drug level measurement and the clinical approach,” Arquivos de Neuro-Psiquiatria, vol. 56, no. 4, pp. 708–713, 1998.
[31]
Scottish Intercollegiate Guidelines Network no. 70, “Diagnosis and management of epilepsy in adults,” 2007, http://www.sign.ac.uk/pdf/sign70.pdf.
[32]
R. M. Werner and D. Polsky, “Comparing the supply of pediatric subspecialists and child neurologists,” Journal of Pediatrics, vol. 146, no. 1, pp. 20–25, 2005.
[33]
M. Weinstock, “Chronic Care: an acute problem,” Hospitals & Health Networks, vol. 78, pp. 40–42, 44–48, 2004.
[34]
P. Rudd, “In search of the gold standard for compliance measurement,” Archives of Internal Medicine, vol. 139, no. 6, pp. 627–628, 1979.
[35]
J. F. Steiner, T. D. Koepsell, S. D. Fihn, and T. S. Inui, “A general method of compliance assessment using centralized pharmacy records. Description and validation,” Medical Care, vol. 26, no. 8, pp. 814–823, 1988.
[36]
R. Sikka, F. Xia, and R. E. Aubert, “Estimating medication persistency using administrative claims data,” American Journal of Managed Care, vol. 11, no. 7, pp. 449–457, 2005.
[37]
C. L. Bryson, D. H. Au, B. Young, M. B. McDonell, and S. D. Fihn, “A refill adherence algorithm for multiple short intervals to estimate refill compliance (ReComp),” Medical Care, vol. 45, no. 6, pp. 497–504, 2007.
[38]
R. A. Hamilton and L. L. Briceland, “Use of prescription-refill records to assess patient compliance,” American Journal of Hospital Pharmacy, vol. 49, no. 7, pp. 1691–1696, 1992.
[39]
C. A. W. Rijcken, H. Tobi, A. C. M. Vergouwen, and L. T. W. de Jong-van den Berg, “Refill rate of antipsychotic drugs: an easy and inexpensive method to monitor patients' compliance by using computerised pharmacy data,” Pharmacoepidemiology and Drug Safety, vol. 13, no. 6, pp. 365–370, 2004.
[40]
J. F. Steiner and A. V. Prochazka, “The assessment of refill compliance using pharmacy records: methods, validity, and applications,” Journal of Clinical Epidemiology, vol. 50, no. 1, pp. 105–116, 1997.
[41]
L. M. Hess, M. A. Raebel, D. A. Conner, and D. C. Malone, “Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures,” Annals of Pharmacotherapy, vol. 40, no. 7-8, pp. 1280–1288, 2006.
[42]
L. N. Ranganathan and S. Ramaratnam, “Rapid versus slow withdrawal of antiepileptic drugs,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD005003, 2006.
[43]
R. S. Greenwood and M. B. Tennison, “When to start and stop anticonvulsant therapy in children,” Archives of Neurology, vol. 56, no. 9, pp. 1073–1077, 1999.
[44]
R. Thorbecke, “Patients with epilepsy who discontinue treatment,” Epilepsy Research. Supplement, vol. 1, pp. 119–124, 1988.
[45]
L. M. Specchio and E. Beghi, “Should antiepileptic drugs be withdrawn in seizure-free patients?” CNS Drugs, vol. 18, no. 4, pp. 201–212, 2004.