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  In this Article
 »  Abstract
 » Introduction
 »  Epilepsy Syndrom...
 »  AED Withdrawal a...
 »  AED Withdrawal a...
 »  Seizure Control ...
 »  Other Benefits a...
 »  When and How to ...
 »  Predictors of Se...
 »  AED Withdrawal F...
 » Conclusions
 »  References
 »  Article Tables

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Table of Contents    
REVIEW ARTICLE
Year : 2014  |  Volume : 62  |  Issue : 1  |  Page : 3-8

Stopping antiepileptic drugs in patients with epilepsy in remission: Why, When and How?


1 Department of Neurology, R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India
2 Department of Clinical and Experimental Epilepsy, Queen Square, London, United Kingdom

Date of Submission29-Nov-2013
Date of Decision30-Nov-2013
Date of Acceptance26-Jan-2014
Date of Web Publication7-Mar-2014

Correspondence Address:
Chaturbhuj Rathore
Department of Neurology, R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.128224

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 » Abstract 

Making a decision to withdraw antiepileptic drugs (AEDs) in patients with epilepsy in remission requires a careful assessment of many patient and disease related factors and the associated risks and benefits. Although unnecessary continuation of AEDs exposes the patients to unwarranted side-effects, a premature withdrawal with subsequent seizure recurrence may be distressing for the patient who otherwise considers himself as cured. Although the final decision needs to be individualized, there are certain guidelines which can help us in making evidence based decision. In this article, we intend to review the current evidence on this subject with an aim of providing a framework of the best clinical practice in this field.


Keywords: Antiepileptic drug withdrawal, epilepsy remission, epilepsy surgery, seizure recurrence


How to cite this article:
Rathore C, Paterson R. Stopping antiepileptic drugs in patients with epilepsy in remission: Why, When and How?. Neurol India 2014;62:3-8

How to cite this URL:
Rathore C, Paterson R. Stopping antiepileptic drugs in patients with epilepsy in remission: Why, When and How?. Neurol India [serial online] 2014 [cited 2017 Sep 24];62:3-8. Available from: http://www.neurologyindia.com/text.asp?2014/62/1/3/128224



 » Introduction Top


The question of whether and when to stop antiepileptic drugs (AEDs) in patients with epilepsy in remission remains extremely controversial and clinicians continue to remain sharply divided in their opinions. [1],[2],[3] Practice of AED withdrawal is largely guided by the personal beliefs and experience rather than the existing evidence. In contrast to the patients in western world, majority of the Indian patients want to stop AEDs at the first opportunity due to the associated financial and social concerns like marriage. Stopping AEDs has obvious advantages: It eliminates the cognitive, teratogenic and other side-effects associated with their use; reduces the financial burden; eliminates the risk of potential drug-interactions; and gives a sense of well-being and complete cure to the patients. However, these benefits need to be balanced against the potential medical and social risks such as loss of driving privileges and self-esteem following a seizure recurrence and the risk of precipitating medically refractory epilepsy in a patient who is well-controlled with AED therapy. [4] Hence, identification of ideal candidates for AED withdrawal and deciding the optimal timing and rate of AED withdrawal are crucial to ensure a successful outcome. In this article, we intend to review the current literature on the subject with a special emphasis on the following aspects: (1) What is the risk of seizure recurrence on planned AED withdrawal? (2) What is the long-term outcome of patients who have seizure recurrence on attempted AED withdrawal and is there any risk of precipitating medically refractory epilepsy? (3) What are the predictors of seizure recurrence on AED withdrawal? (4) What is the ideal timing and rate of AED withdrawal? (5) Can AEDs be withdrawn following successful epilepsy surgery?


 » Epilepsy Syndromes and AED Withdrawal Top


The type of epilepsy syndrome greatly influences the decision to withdraw AEDs and the subsequent outcome. Certain epilepsy syndromes in children like benign rolandic epilepsy almost always remit and AEDs can be safely and successfully withdrawn in the majority of these patients. On the other hand, syndromes such as juvenile myoclonic epilepsy and reading epilepsy almost never remit and seizure relapse is almost certain to occur if AEDs are withdrawn. These syndromes, with well-defined prognosis, however, form a small part of overall epilepsy population. Approximately, three quarters of all patients have syndromes with intermediate prognosis and these are the patients in whom it is difficult to predict the precise outcome on an individual basis. The majority of the discussion in the following sections is centered on these patients.


 » AED Withdrawal and Seizure Recurrence: Adults Top


Many studies, mostly retrospective observational studies and other uncontrolled trials have reported variable rates of seizure recurrence following AED withdrawal in patients with epilepsy in remission. Only three studies have reported the risk of seizure recurrence where patients were randomized to AED withdrawal versus continued treatment. The earliest and largest prospective randomized study was by the Medical Research Council (MRC) AED Withdrawal Group in which 1013 patients who had been seizure free for at least 2 years were randomized to continued AEDs versus slow withdrawal over 6 months. [5] At 2 years after randomization, relapse rate was 22% in the continued-treatment group compared to 41% in the withdrawal group. The difference in the recurrence risk between the two groups was highest at 9 months but became equal after 2 years of follow-up. This study represented real life clinical scenario and included unselected patient population where 15% patients had developmental delay and 20% had some form of neurological insult. The major factors associated with a higher risk of seizure recurrence were history of generalized tonic-clonic seizures (relative risk [RR], 3.4; 95% confidence interval [CI], 1.48-7.84), history of myoclonic seizures (RR, 1.85; 95% CI, 1.09-3.12), ≥2 AEDs at randomization (RR, 1.79; 95% CI, 1.34-2.39) and history of seizures after starting the treatment (RR, 1.57; 95% CI, 1.1-2.24). Patients with a seizure freedom of >5 years were less likely to have recurrence when compared with those with a seizure freedom of <2.5 years [RR, 0.47; 95% CI, 0.32-0.69]. In another study by Specchio et al., 330 patients who were seizure free for at least 2 years while on stable monotherapy were offered AED withdrawal. [6] After discussion of risks and benefits, 225 patients opted for AED discontinuation while 105 decided to continue treatment. At a mean follow-up period of 48 months, 29 (28%) patients who continued treatment had a relapse compared with 113 (50%) of those entering the withdrawal program. The risk of seizure relapse was 2.9 times higher in the patients who discontinued AEDs. In a truly randomized study, Lossius et al., randomized patients who were seizure-free for >2 years on monotherapy, to AED withdrawal (n = 79) and non-withdrawal (n = 81) groups. [7] Patients were followed-up in a double blinded manner for 12 months or until seizure relapse when patients in non-withdrawal group entered into an open withdrawal arm with a median follow-up of 47 months. At 12 months, seizure relapse was noted in 15% of the withdrawal group and 7% of the non-withdrawal group (RR, 2.46; 95% CI, 0.85-7.08; P = 0.095). In open follow-up, seizure relapse rate was 27% after a median of 41 months off medication. Lower relapse rates in this study were party related to strict patient selection criteria; patients with a high likelihood of relapse like those with juvenile myoclonic epilepsy, patients of primary generalized epilepsy with abnormal electroencephalogram (EEG), those on polytherapy and those with mental retardation were excluded. This study, although with small numbers when compared with MRC study, indicated that in carefully selected patients relapse rate is as low as 15% at 1 year.

Apart from these individual studies, several meta-analyses, systematic reviews and practice parameters have been published on this subject. The earliest meta-analysis by Berg and Shinnar in 1992 which included 25 studies, reported that the relapse rate at 1 year was 25% (95% CI, 21-30) and at 2 years was 29% (95% CI, 24-34). [8] The factors associated with higher risk of relapse were adult-onset epilepsy, symptomatic cause and abnormal EEG. The American Academy of Neurology practice parameter in 1996 which included 17 studies, reported that the seizure recurrence rates after AED discontinuation were 31.2% for children and 39.4% for adults (pooled, weighted averages). [9] Two other large systematic reviews reported that proportion of patients who have relapse during or after AED withdrawal ranges from 12% to 66% respectively (mean 34%, 95% CI, 27-43). [3],[10]

Overall, it can be concluded that AED withdrawal increases the risk of immediate seizure recurrence by two fold which also can be minimized by the careful selection of patients. However, after 2 years of AED withdrawal, risk of seizure recurrence in patients who have undergone AED withdrawal appears to be same as that of those who continue on AED therapy. [5],[6]


 » AED Withdrawal and Seizure Recurrence: Children Top


Except in some of the benign childhood epilepsy syndromes, risk of relapse following AED withdrawal in children remains same as that in adults. In a truly randomized prospective trial of AED withdrawal in children by Peters et al., 161 children with newly diagnosed epilepsy who had become seizure free within 2 months of starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). [11] At 2 years after randomization, the early withdrawal cohort had a relapse rate of 49%, compared with 48% for the late withdrawal cohort. At the end of median follow-up of 42 months, 81% had a terminal remission of at least 1 year with no difference between the groups. These results are similar to other prospective withdrawal trials in the pediatric population and indicate a twofold risk of immediate seizure relapse on AED withdrawal with no difference after 2 years. [12],[13]


 » Seizure Control after Relapse Top


The most important question relating to AED withdrawal is not the risk of seizure relapse but seizure control subsequent to the relapse. In case of a recurrence, patients are anxious to know whether the seizures will be as well-controlled as before or whether they risk the development of medically refractory epilepsy. In a long-term prospective follow-up study in children, 30% of 260 children developed seizures on AED withdrawal. [14] Of these only 03 (1%) children developed medically refractory epilepsy. Similarly, in the long-term follow-up of the MRC study cohort (409 patients) who developed recurrence, terminal 1-year remission was achieved in 95% of patients and terminal 2-year remission was achieved in 90% of patients. [15] Importantly, there was no difference in the outcome of patients who had undergone early AED withdrawal versus those who had late withdrawal of AEDs. In this study, the factors associated with poor seizure control after recurrence were short seizure-free interval before withdrawal, partial seizures at recurrence and history of previous seizures while receiving treatment. Authors suggested that AED withdrawal does not influence the natural history of epilepsy. Contrary to these results, in a systematic review involving 14 studies, Schmidt and Löscher reported that 19% (95% CI, 15-24%) of patients who had seizure recurrence on AED withdrawal did not achieve the same seizure control as before. [10] Factors associated with poor outcome following recurrence were symptomatic etiology, partial epilepsy and cognitive deficits. However, all the studies in this review were small non-population based case series and none were systematic or randomized studies. [10] In the absence of a long-term control group, it is difficult to decide whether the development of medically refractory epilepsy occurs as a part of natural history of disease or is precipitated by AED withdrawal. However, overall results indicate that the risk of precipitating refractory epilepsy is very small but caution should be exercised in certain predisposed groups.


 » Other Benefits and Risks of AED Withdrawal Top


One of the potential benefits of successful AED withdrawal is improved psycho-social profile and quality of life. However, this has not been definitively proven. In the randomized trial by Hessen et al., patients who had undergone AED withdrawal had improved in certain neuropsychological functions. [16] Similar improved feeling of well-being on AED withdrawal was reported in the MRC study group. [4] This potential benefit needs to be balanced with the adverse neuropsychological effects associated with a seizure recurrence. Overall there is evidence that the cognitive functions requiring concentration and rapid motor coordination may improve following AED withdrawal.

There is limited data on the risk of status epilepticus and mortality following AED withdrawal. In the MRC trial, there were two seizure related deaths, both in the group with continued treatment. In three large populations based studies which involved 1777 patients followed-up for 5-20 years, 70% of patients discontinued AED. [17],[18],[19] There were only four deaths (two related to status epileptics and two were sudden unexplained death in epilepsy) in this whole cohort and none of them discontinued AED. Based upon present evidence, overall risk of status epilepticus and death related to AED withdrawal is negligible.


 » When and How to Withdraw AEDs Top


There are no definite guidelines concerning the optimal timing of AED withdrawal and the evidence is lacking especially in adults. A Cochrane systematic review, which included seven studies, evaluated the effect of early versus late (<2 years vs. >2 years of seizure freedom) AED withdrawal on seizure recurrence in children. [20] In 924 randomized children, the pooled RR for the seizure relapse in early withdrawal group was 1.32 (95% CI, 1.02-1.70). Similarly, in the randomized trial by Peters et al., AED withdrawal after 6 months of seizure freedom was associated with a relatively higher risk of seizure relapse, indicating that 6 months is probably too early to consider AED withdrawal. [11] Overall, a 2 year of seizure freedom appears to be reasonable time period before considering AED withdrawal in children.

Evidence is more inconsistent in adults. The majority of studies have used a variable period of 2-5 years of seizure freedom before considering AED withdrawal. In the MRC study as well as in other systematic reviews, a shorter duration of seizure freedom of <2.5 years before attempted AED withdrawal was associated with a higher risk of seizure relapse. Camfield, in a review published in 2008, suggested a seizure free period of at least 4 years before attempting AED withdrawal. [21]

Once a decision for AED withdrawal has been made, the next question is how to withdraw. The various studies have used different protocols for the same and there is no apparent consensus between the experts. In the only randomized controlled trial, 149 children were randomized to either rapid withdrawal over 6 weeks (n = 81) or slow withdrawal over 9 months (n = 68). [22] In patients on polytherapy, the drugs were tapered sequentially. Risk of seizure recurrence was similar in both groups at every year up to 5 years. A trend toward higher recurrence rate was noted during the first 2 years in patients in rapid withdrawal group and during 4 th and 5 th year in patients in slow withdrawal group. In another study, there was no difference between relapse rates in 57 children who were randomized to AED withdrawal over 1 month versus over 6 months. [23] However, this study included only a small number of patients. There have been no studies in adults evaluating this aspect of AED withdrawal. Based upon these small number of studies, the Cochrane systematic review could not provide any reliable conclusions. [24] In the absence of definitive data, the decision needs to be individualized and a middle path approach of withdrawal over 3-6 months is justified.

There is a lack of data regarding withdrawal of specific drugs and partial withdrawal of drugs. Few studies have reported that the withdrawal of carbamazepine was associated with lower risk of relapse. [7],[25] However, this may be spurious as patients with milder epilepsy might have been on carbamazepine which is often the first drug used in partial epilepsy and this requires further study.


 » Predictors of Seizure Recurrence on AED Withdrawal Top


As mentioned in the previous discussion, many factors have been found to be associated with a higher risk of seizure relapse following AED withdrawal [Table 1]. [5],[6],[7],[8],[9],[26],[27],[28],[29] Several studies have suggested predictive models based upon combination of various prognostic factors. In one study of 97 children who discontinued AEDs after 1 year of seizure-freedom, relapse occurred in 39% of patients at 2 years. On multivariate analysis the following factors were found to be predictive of seizure recurrence: female sex, abnormal neurologic examination, age of onset <120 months and focal seizures. The recurrence risk was 0 for those with no risk factors while it was 95% with all the risk factors. [30] The MRC study group also developed a prognostic index for calculating the risk of seizure recurrence over 1-2 years by combining the following factors: Age 16 or more; use of more than one AED; seizure occurrence after start of drug treatment; history of primarily or secondarily generalized tonic-clonic seizures; history of myoclonic seizures; an abnormal EEG. [31] In spite of all the studies suggesting various prognostic factors, no factor or model can exactly predict the risk of seizure recurrence in an individual patient and hence each patient needs to be counseled on an individual basis.
Table 1: Factors associated with a higher risk of seizure relapse

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 » AED Withdrawal Following Epilepsy Surgery Top


Freedom from AEDs is one of the major aims of the epilepsy surgery. [32],[33] There have been no published randomized controlled trials or guidelines of AED withdrawal in the post-operative period and the practice of AED withdrawal varies widely across the centers. In a systematic review, Schmidt et al., identified six studies that had addressed AED withdrawal following epilepsy surgery. [34] These studies included 611 (range: 57-210) heterogeneous groups of patients who underwent different epilepsy surgery procedures for various pathological substrates. Whereas only fewer than 50% seizure-free adult patients underwent elective AED withdrawal, nearly 70% of seizure-free children discontinued AEDs. During follow-up periods ranging from 1 to 5 years, seizures recurred in 16-36% of patients. The retrospective nature of the studies precluded reliable analysis of risk factors for recurrence. [34],[35]

We analyzed the feasibility and safety of AED withdrawal in 310 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who had undergone anterior temporal lobectormy and were prospectively followed-up. [36] AED withdrawal was attempted in 258 patients starting at 3 months following surgery in those on duo therapy and at 1 year in those who were on monotherapy. All patients underwent a slow withdrawal over 2 years in a pre-defined protocol. At the mean follow-up period of 8.0 ± 2.0 years, AED were stopped in 52% of patients. Seizures recurred in 64 patients during or after AED withdrawal, 90% of them again became seizure free after reinstitution of AED. Longer duration of epilepsy, absence of HS on pathology and abnormal EEG at 1 st post-operative year predicted seizure recurrence. [36],[37] This data indicated that AEDs can be safely stopped in approximately half of carefully selected patients of MTLE-HS following temporal lobectomy. Results are less optimistic following extra-temporal surgeries where AED could be stopped in only 25-27% of patients. [38],[39] Seizure recur in 40-52% of patients following AED withdrawal in extra temporal surgeries and AED withdrawal needs to be more cautiously approached in these patients. In this group, patients with longer duration of epilepsy, abnormal post-operative EEG and those with diffuse pathologies such as dysplasia and gliosis are at a higher risk of recurrence. [38],[39]


 » Conclusions Top


Given that Epilepsy is a constellation of various syndromes and sub-syndromes, each with a markedly different prognosis, a "one shoe for all" approach is not feasible while contemplating AED withdrawal in patients with epilepsy in remission[Table 2]. Barring a few well-defined syndromes, prognosis following AED withdrawal is uncertain in the majority of patients which makes it necessary to carefully consider many factors before deciding to withdraw AEDs. The available literature has its own limitations with the majority of studies being small observational studies with short follow-up periods. In view of this a blanket all or none approach cannot be reliably employed and an individual decision should be made for each patient in accordance with their wishes.
Table 2: Salient points for AED withdrawal in patients with epilepsy in remission

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 » References Top

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4.Jacoby A, Johnson A, Chadwick D. Psychosocial outcomes of antiepileptic drug discontinuation. The Medical Research Council Antiepileptic Drug Withdrawal Study Group. Epilepsia 1992;33:1123-31.  Back to cited text no. 4
    
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7.Lossius MI, Hessen E, Mowinckel P, Stavem K, Erikssen J, Gulbrandsen P, et al. Consequences of antiepileptic drug withdrawal: A randomized, double-blind study (Akershus Study). Epilepsia 2008;49:455-63.  Back to cited text no. 7
    
8.Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: A meta-analysis. Neurology 1994;44:601-8.  Back to cited text no. 8
    
9.Practice parameter: A guideline for discontinuing antiepileptic drugs in seizure-free patients - Summary statement. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1996;47:600-2.  Back to cited text no. 9
    
10.Schmidt D, Löscher W. Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: A review of current clinical experience. Acta Neurol Scand 2005;111:291-300.  Back to cited text no. 10
    
11.Peters AC, Brouwer OF, Geerts AT, Arts WF, Stroink H, van Donselaar CA. Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Neurology 1998;50:724-30.  Back to cited text no. 11
    
12.Verrotti A, Morresi S, Basciani F, Cutarella R, Morgese G, Chiarelli F. Discontinuation of anticonvulsant therapy in children with partial epilepsy. Neurology 2000;55:1393-5.  Back to cited text no. 12
    
13.Geerts AT, Niermeijer JM, Peters AC, Arts WF, Brouwer OF, Stroink H, et al. Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy. Neurology 2005;64:2136-8.  Back to cited text no. 13
    
14.Camfield P, Camfield C. The frequency of intractable seizures after stopping AEDs in seizure-free children with epilepsy. Neurology 2005;64:973-5.  Back to cited text no. 14
    
15.Chadwick D, Taylor J, Johnson T. Outcomes after seizure recurrence in people with well-controlled epilepsy and the factors that influence it. The MRC Antiepileptic Drug Withdrawal Group. Epilepsia 1996;37:1043-50.  Back to cited text no. 15
    
16.Hessen E, Lossius MI, Reinvang I, Gjerstad L. Slight improvement in mood and irritability after antiepileptic drug withdrawal: A controlled study in patients on monotherapy. Epilepsy Behav 2007;10:449-55.  Back to cited text no. 16
    
17.Callenbach PM, Westendorp RG, Geerts AT, Arts WF, Peeters EA, van Donselaar CA, et al. Mortality risk in children with epilepsy: The Dutch study of epilepsy in childhood. Pediatrics 2001;107:1259-63.  Back to cited text no. 17
    
18.Camfield CS, Camfield PR, Veugelers PJ. Death in children with epilepsy: A population-based study. Lancet 2002;359:1891-5.  Back to cited text no. 18
    
19.Shinnar S, O′Dell C, Berg AT. Mortality following a first unprovoked seizure in children: A prospective study. Neurology 2005;64:880-2.  Back to cited text no. 19
    
20.Sirven JI, Sperling M, Wingerchuk DM. Early versus late antiepileptic drug withdrawal for people with epilepsy in remission. Cochrane Database Syst Rev 2001;3:CD001902.  Back to cited text no. 20
    
21.Camfield P, Camfield C. When is it safe to discontinue AED treatment? Epilepsia 2008;49 Suppl 9:25-8.  Back to cited text no. 21
    
22.Tennison M, Greenwood R, Lewis D, Thorn M. Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period. N Engl J Med 1994;330:1407-10.  Back to cited text no. 22
    
23.Serra JG, Montenegro MA, Guerreiro MM. Antiepileptic drug withdrawal in childhood: Does the duration of tapering off matter for seizure recurrence? J Child Neurol 2005;20:624-6.  Back to cited text no. 23
    
24.Ranganathan LN, Ramaratnam S. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database Syst Rev 2006 ;2:CD005003.  Back to cited text no. 24
    
25.Chadwick D. Does withdrawal of different antiepileptic drugs have different effects on seizure recurrence? Further results from the MRC Antiepileptic Drug Withdrawal Study. Brain 1999;122 (Pt 3):441-8.  Back to cited text no. 25
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26.Shinnar S, Berg AT, Moshé SL, Kang H, O′Dell C, Alemany M, et al. Discontinuing antiepileptic drugs in children with epilepsy: A prospective study. Ann Neurol 1994;35:534-45.  Back to cited text no. 26
    
27.Andersson T, Braathen G, Persson A, Theorell K. 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 1997;38:225-32.  Back to cited text no. 27
    
28.Cardoso TA, Coan AC, Kobayashi E, Guerreiro CA, Li LM, Cendes F. Hippocampal abnormalities and seizure recurrence after antiepileptic drug withdrawal. Neurology 2006;67:134-6.  Back to cited text no. 28
    
29.Brodie MJ, Kwan P. Epilepsy in elderly people. BMJ 2005;331:1317-22.  Back to cited text no. 29
    
30.Dooley J, Gordon K, Camfield P, Camfield C, Smith E. Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: A prospective study. Neurology 1996;46:969-74.  Back to cited text no. 30
    
31.Prognostic index for recurrence of seizures after remission of epilepsy. Medical Research Council Antiepileptic Drug Withdrawal Study Group. BMJ 1993;306:1374-8.  Back to cited text no. 31
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32.Taylor DC, McMacKin D, Staunton H, Delanty N, Phillips J. Patients′ aims for epilepsy surgery: Desires beyond seizure freedom. Epilepsia 2001;42:629-33.  Back to cited text no. 32
    
33.Wilson SJ, Saling MM, Kincade P, Bladin PF. Patient expectations of temporal lobe surgery. Epilepsia 1998;39:167-74.  Back to cited text no. 33
    
34.Schmidt D, Baumgartner C, Löscher W. Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: A review of current clinical experience. Epilepsia 2004;45:179-86.  Back to cited text no. 34
    
35.Berg AT. Stopping antiepileptic drugs after successful surgery: What do we know? And what do we still need to learn? Epilepsia 2004;45:101-2.  Back to cited text no. 35
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36.Rathore C, Panda S, Sarma PS, Radhakrishnan K. How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy? Epilepsia 2011;52:627-35.  Back to cited text no. 36
    
37.Rathore C, Sarma SP, Radhakrishnan K. Prognostic importance of serial postoperative EEGs after anterior temporal lobectomy. Neurology 2011;76:1925-31.  Back to cited text no. 37
    
38.Park KI, Lee SK, Chu K, Jung KH, Bae EK, Kim JS, et al. Withdrawal of antiepileptic drugs after neocortical epilepsy surgery. Ann Neurol 2010;67:230-8.  Back to cited text no. 38
    
39.Menon R, Rathore C, Sarma SP, Radhakrishnan K. Feasibility of antiepileptic drug withdrawal following extratemporal resective epilepsy surgery. Neurology 2012;79:770-6.  Back to cited text no. 39
    



 
 
    Tables

  [Table 1], [Table 2]

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