Discontinuation of AEDs: When and how?

Taoufik Alsaadi, Mustafa Shakra, Lamya Turkawi

Department of Neurology, Sheikh Khalifa Medical City, Abu Dhabi, UAE.

DOI: 10.4236/health.2013.56A1004                

Abstract

Once a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the decision to discontinue AED should be balanced against continuation of AED therapy indefinitely. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs. However, there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period. There are several factors that would increase risk of recurrences which will be reviewed and discussed. As a consequence, the decision to withdraw or withhold treatment must be still individualized. In any patient, the decision to discontinue treatment should also take into effect the social aspects like driving license, job and leisure activities as well as emotional and personal factors and patients with adverse effects or drug interactions. Patients will ultimately have to decide themselves whether they wish to discontinue drug treatment.

Keywords

Epilepsy; Discontinuation of Antiepileptic Drugs (AEDs); Outcome of Recurrences

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hauser, W.A., Annegers, J.F. and Rocca, W.A. (1996) Descriptive epidemiology of epilepsy: Contributions of population-based studies from Rochester, Minnesota. Mayo Clinic Proceedings, 71, 576-586. doi:10.4065/71.6.576
[2]	Sillanpaa, M., Jalava, M., Kaleva, O. and Shinnar, S. (1998) Long-term prognosis of seizures with onset in childhood. The New England Journal of Medicine, 338, 1715-1722. doi:10.1056/NEJM199806113382402
[3]	Cockerell, O.C., Johnson, A.L., Sander, J.W. and Shorvon, S.D. (1997) Prognosis of epilepsy: A review and further analysis of the first nine years of the British National General Practice Study of Epilepsy, a prospective population-based study. Epilepsia, 38, 31-46. doi:10.1111/j.1528-1157.1997.tb01075.x
[4]	Sillanpaa, M. and Schmidt, D. (2006) Natural history of treated childhood onset epilepsy: Prospective, long-term population-based study. Brain, 129, 617-624. doi:10.1093/brain/awh726
[5]	Pitkanen, A. (2002) Efficacy of current antiepileptics to prevent neurodegeneration in epilepsy models. Epilepsy Research, 50, 141-160. doi:10.1016/S0920-1211(02)00076-1
[6]	Temkin, N.R. (2001) Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: Meta-analysis of controlled trials. Epilepsia, 42, 515-524. doi:10.1046/j.1528-1157.2001.28900.x
[7]	Annegers, J.F., Hauser, W.A. and Elveback, L.R. (1979) Remission of seizures and relapse in patients with epilepsy. Epilepsia, 20, 729-737. doi:10.1111/j.1528-1157.1979.tb04857.x
[8]	Nicoletti, A., Sofia, V., Vitale, G., Bonelli, S.I., Bejarano, V., Bartalesi, F., Tran, D.S., Preux, P.M., Zappia, M. and Bartoloni, A. (2009) Natural history and mortality of chronic epilepsy in an untreated population of rural Bolivia: A follow-up after 10 years. Epilepsia, 50, 2199- 2206. doi:10.1111/j.1528-1167.2009.02174.x
[9]	Watts, A.E. (1992) The natural history of untreated epilepsy in a rural community in Africa. Epilepsia, 33, 464- 468. doi:10.1111/j.1528-1157.1992.tb01692.x
[10]	St. Louis, E.K. (2009) Minimizing AED adverse effects: Improving quality of life in the interictal state in epilepsy care. Current Neuropharmacology, 7, 106-114. doi:10.2174/157015909788848857
[11]	Harden, C.L., Meador, K.J., Pennell, P.B., et al. (2009) Management issues for women with epilepsy—Focus on pregnancy (an evidence based review): Part II. Teratogenesis and perinatal outcomes. Epilepsia, 50, 1237- 1246. doi:10.1111/j.1528-1167.2009.02129.x
[12]	Patsalos, P.N. and Perucca, E. (2003) Clinically important drug interactions in epilepsy: Interactions between antiepileptic drugs and other drugs. The Lancet Neurology, 2, 473-481. doi:10.1016/S1474-4422(03)00483-6
[13]	Begley, C.E., Annegers, J.F., Lairson, D.R. and Reynolds, T.F. (1999) Estimating the cost of epilepsy. Epilepsia, 40, 8-13. doi:10.1111/j.1528-1157.1999.tb00941.x
[14]	Kwan, P. and Brodie, M.J. (2001) Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet, 357, 216-222. doi:10.1016/S0140-6736(00)03600-X
[15]	Fischbacher, E. (1982) Effect of reduction of anticonvulsants on wellbeing. British Medical Journal, 285, 423- 424.
[16]	Theodore, W.H. and Porter, R.J. (1983) Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy. Annals of Neurology, 13, 320-324. doi:10.1002/ana.410130316
[17]	Mula, M. and Monaco, F. (2009) Antiepileptic drugs and psychopathology: An update. Epileptic Disorders, 11, 1- 9.
[18]	Ortinski, P. and Meador, K.J. (2004) Cognitive side effects of antiepileptic drugs. Epilepsy & Behavior, 5, S60- S65. doi:10.1016/j.yebeh.2003.11.008
[19]	Lossius, M.I., Hessen, E., Mowinckel, P., Stavem, K., Erikssen, J., Gulbrandsen, P. and Gjerstad, L. (2008) Consequences of antiepileptic drug withdrawal: A doubleblind, randomized study (Akershus Study). Epilepsia, 49, 455-463. doi:10.1111/j.1528-1167.2007.01323.x
[20]	Collaborative Group for Epidemiology of Epilepsy (1986) Adverse reactions to antiepileptic drugs: A multicenter survey of clinical practice. Epilepsia, 27, 323-330. doi:10.1111/j.1528-1157.1986.tb03549.x
[21]	Specchio, L.M. and Beghi, E. (2004) Should antiepileptic drugs be withdrawn in seizure-free patients? CNS Drugs, 18, 201-212. doi:10.2165/00023210-200418040-00001
[22]	MRC Antiepileptic Drug Withdrawal Group (1991) Randomized study of antiepileptic drug withdrawal in patients in remission. Lancet, 337, 1175-1180.
[23]	Overweg, J., Binnie, C.D., Oosting, J. and Rowan, A.J. (1987) Clinical and EEG prediction of seizure recurrence following antiepileptic drug withdrawal. Epilepsy Research, 1, 272-283. doi:10.1016/0920-1211(87)90002-7
[24]	Matricardi, A., Bertamino, F. and Risso, D. (1995) Discontinuation of antiepileptic therapy: A retrospective study of 86 children and adolescents. The Italian Journal of Neurological Sciences, 16, 613-622. doi:10.1007/BF02230911
[25]	Callaghan, N., Garrett, A. and Goggin, T. (1988) Withdrawal of anticonvulsant drugs in patients free of seizures for two years: A prospective study. The New England Journal of Medicine, 318, 942-946. doi:10.1056/NEJM198804143181502
[26]	Berg, A.T. and Shinnar, S. (1994) Relapse following discontinuation of antiepileptic drugs: A meta-analysis. Neurology, 44, 601-608. doi:10.1212/WNL.44.4.601
[27]	Shinnar, S., Berg, A.T., Moshe, S.L., et al. (1994) Discontinuing antiepileptic drugs in children with epilepsy: A prospective study. Annals of Neurology, 35, 534-545. doi:10.1002/ana.410350506
[28]	Todt, H. (1984) The late prognosis of epilepsy in childhood: results of a prospective follow-up study. Epilepsia, 25, 137-144. doi:10.1111/j.1528-1157.1984.tb04169.x
[29]	Thurston, J.H., Thurston, D.L., Hixon, B.B. and Keller, A.J. (1982) Prognosis in childhood epilepsy: Additional follow-up of 148 children 15 to 23 years after withdrawal of anticonvulsant therapy. The New England Journal of Medicine, 306, 831-836. doi:10.1056/NEJM198204083061403
[30]	Sillanpaa, M. and Schmidt, D. (2006) Prognosis of seizure recurrence after stopping antiepileptic drugs in seizure-free patients: A long-term population-based study of childhood-onset epilepsy. Epilepsy & Behavior, 8, 713- 719. doi:10.1016/j.yebeh.2006.02.014
[31]	Sirven, J.I., Sperling, M. and Wingerchuk, D.M. (2011) Early versus late antiepileptic drug withdrawal for people with epilepsy in remission. Cochrane Database of Systematic Reviews, CD001902.
[32]	Sillanpaa, M., Jalava, M., Kaleva, O. and Shinnar, S. (1998) Long-term prognosis of seizures with onset in childhood. The New England Journal of Medicine, 338, 1715-1722. doi:10.1056/NEJM199806113382402
[33]	Chadwick, D., Taylor, J. and Johnson, T. (1996) Outcomes after seizure recurrence in people with well-controlled epilepsy and the factors that influence it. Epilepsia, 37, 1043-1050.
[34]	Panayiotopoulos, C.P. (1998) Absence epilepsies. In: Engel Jr., J. and Pedley, T.A., Eds., Epilepsy: A Comprehensive Textbook. Lippincott-Raven Publishers, Philadelphia, 2327-2346.
[35]	Plouin, P. (1998) Benign familial neonatal convulsions and benign idiopathic neonatal convulsions. In: Engel Jr., J. and Pedley, T.A., Eds., Epilepsy: A Comprehensive Textbook, Lippincott-Raven Publishers, Philadelphia, 2247- 2255.
[36]	Loiseau, P., Pestre, M., Dartigues, J.F., Commenges, D., Barberger-Gateau, C. and Cohadon, S. (1983) Long-term prognosis in two forms of childhood epilepsy: Typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci. Annals of Neurology, 13, 642-648. doi:10.1002/ana.410130610
[37]	Delgado-Escueta, A.V. and Enrile-Bacsal, F. (1984) Juvenile myoclonic epilepsy of Janz. Neurology, 34, 285-294. doi:10.1212/WNL.34.3.285
[38]	Camfield, C.S. and Camfield, P.R. (2009) Juvenile myoclonic epilepsy 25 years after seizure onset: A population-based study. Neurology, 73, 1041-1045. doi:10.1212/WNL.0b013e3181b9c86f
[39]	Matricardi, M., Brinciotti, M. and Benedetti, P. (1989) Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy. Epilepsia, 30, 582-589. doi:10.1111/j.1528-1157.1989.tb05476.x
[40]	Marson, A.G., Kadir, Z.A., Hutton, J.L. and Chadwick, D.W. (1997) The new antiepileptic drugs: A systematic review of their efficacy and tolerability. Epilepsia, 38, 859-880. doi:10.1111/j.1528-1157.1997.tb01251.x
[41]	Kimura, M., Yoshino, K. and Suzuki, N. (2000) Seizure recurrence after reduction of an antiepileptic drug in patients with unprovoked seizures and severe neurological abnormalities. Psychiatry and Clinical Neurosciences, 54, 41-44. doi:10.1046/j.1440-1819.2000.00635.x
[42]	Arts, W.F., Visser, L.H., Loonen, M.C., et al. (1988) Follow-up of 146 children with epilepsy after withdrawal of antiepileptic therapy. Epilepsia, 29, 244-250. doi:10.1111/j.1528-1157.1988.tb03713.x
[43]	American Academy of Pediatrics (1985) Behavioral and cognitive effects of anticonvulsant therapy. Pediatrics, 76, 644-647.
[44]	Theodore, W.H. and Porter, R.J. (1983) Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy. Annals Neurology, 13, 320-324. doi:10.1002/ana.410130316
[45]	Andersson, T., Braathen, G., Persson, A. and Theorell, K. (1997) A comparison between one and three years of treatment in uncomplicated childhood epilepsy: A prospective study, II: The EEG as predictor of outcome after withdrawal of treatment. Epilepsia, 38, 225-232. doi:10.1111/j.1528-1157.1997.tb01101.x
[46]	Tinuper, P., Avoni, P., Riva, R., Provini, F., Lugaresi, E. and Baruzzi, A. (1996) The prognostic value of the electroencephalogram in antiepileptic drug withdrawal in partial epilepsies. Neurology, 47, 76-78. doi:10.1212/WNL.47.1.76
[47]	Uesugi, H., Kojima, T., Miyasaka, M., et al. (1994) Discontinuation of antiepileptic drug treatment in controlled seizure patients. The Japanese journal of psychiatry and neurology, 48, 255-258.
[48]	Salinsky, M., Kanter, R. and Dasheiff, R.M. (1987) Effectiveness of multiple EEGs in supporting the diagnosis of epilepsy: An operational curve. Epilepsia, 28, 331-334. doi:10.1111/j.1528-1157.1987.tb03652.x
[49]	Marsan, C.A. and Zivin, L.S. (1970) Factors related to the occurrence of typical paroxysmal abnormalities in the EEG records of epileptic patients. Epilepsia, 11, 361-381. doi:10.1111/j.1528-1157.1970.tb03903.x
[50]	Ranganathan, L.N. and Ramaratnam, S. (2006) Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database of Systematic Reviews, CD005003. doi:10.1002/14651858.CD005003.pub2
[51]	Tennison, M., Greenwood, R., Lewis, D. and Thorn, M. (1994) Discontinuing antiepileptic drugs in children with epilepsy: A comparison of a six-week and a nine-month taper period. The New England Journal of Medicine, 330, 1407-1410. doi:10.1056/NEJM199405193302002
[52]	Schmidt, D. and Lo¨scher, W. (2005) Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: A review of current clinical experience. Acta Neurological Scandmavica, 111, 291-300. doi:10.1111/j.1600-0404.2005.00408.x