The document discusses the complexities and considerations surrounding the discontinuation of antiepileptic drugs (AEDs) in patients with well-controlled adult-onset focal epilepsy. Despite the potential risks of relapse after cessation, the overall long-term outcomes suggest that many patients can safely withdraw from treatment without significant negative consequences. It emphasizes the need for individualized assessment based on seizure history, brain lesions, and other factors influencing the risk of recurrence.

1. “Is it advisable to taper medication in well-
controlled patients with symptomatic adult-
onset focal epilepsy” ?
Dr Pramod Krishnan, M.D, D.M
Consultant Neurologist and Epileptologist
Head of the Department of Neurology,
Manipal Hospital, Bengaluru.

2. “The ideal objective of treating a person with epilepsy is to induce
remission by usage of antiepileptic drugs (AEDs) and ultimately stop
the AEDs without causing seizure recurrence”.
Schmidt D, et al. Drug treatment of epilepsy in adults. BMJ 2014;348:g254.

3. However,…
• We do not fully understand epileptogenesis.
• We do not fully understand the natural history of epilepsy.
• Therefore, predicting seizure control or relapse in an individual
patient is based more on probability than any accurate estimate.

4. Behavioural issues
Memory and Cognitive issues
Sedation and Insomnia
Learning issues
Cost of medications, hospital visits
Bone health
Other organ system adverse effects
Teratogenicity
Weight gain and cosmetic issues
Problems with comedications
Sense of being ‘unwell’, ‘still a patient’
Social stigma of being on AEDs
Fear of being on unnecessary treatment
Problems with continued use of AEDs

5. Pitfalls of stopping AEDs
• Sense of anxiety, fear, insecurity regarding relapse.
• Relapse of epilepsy, and the distress and dejection that follows.
• Effect of seizure relapse on employment, marriage, driving.
• Risk of injury, accidents, SUDEP.
• Medicolegal issues if the patient was not counselled adequately,
poor appreciation of the risks by the patient.
• Risk of refractoriness, or longer time for remission.

6. Approach to AED discontinuation
• AEDs are often withdrawn in a patients entering prolonged
remission, especially in India.
• Surprisingly, class I evidence on the consequences of doing so on
seizure outcome and general health are rather limited.
Braun KP, et al. Curr Opin Neurol 2014; 27(2):219–26.
• The decision to continue or to stop AED treatment is a difficult
one and requires a full assessment of the risk- benefit balance of
AED discontinuation for the individual patient.
Rathore C, Paterson R. Neurology India 2014. Vol 62.

7. Populations Recurrence rate Year
Adults and children.
25 studies, n= 5354
25% at 1 yr. (95%CI 21–30)
29% at 2 yrs. (95%CI 24–34)
range 12–67%
1994
Adults and children
9 studies, n= 1813
45%
range 23–66%
2004
Adults and children
13 studies, n= 2336
34% (95%CI 27–43)
range 12–66%
2005
Meta-analyses or systematic reviews on seizure relapse following AED
reduction in medically treated cohorts

8. Would this approach be different in
symptomatic epilepsy?
• The general impression would be that patients with symptomatic
epilepsy would fare worse than others.
• However, ‘symptomatic epilepsy’ is heterogenous, encompassing
various etiologies of differing epileptogenicity.
• Long term seizure freedom would be unlikely in patients with
lesions like MTS, FCD, major cortical malformations, TSC
complex etc.
• AED withdrawal would therefore be relevant to lesions where
prolonged seizure freedom with AED is feasible.

9. Caveats to remember….
• Most large studies focused on epilepsy patients in general (adults
and children), not only the symptomatic epilepsy group.
• The very nature of the inclusion criteria in many studies,
essentially ruled out patients with severe brain disease or highly
epileptogenic lesions.
• Therefore, the evidence presented would probably be relevant only
to patients with symptomatic epilepsy of a milder degree, due to
lesions with low epileptogenicity.

10. A prospective, multi-centre, randomized, unblinded study of slow AED
withdrawal Vs AED continuation in 1013 patients with seizure freedom of atleast
2 years and without any other progressive medical illness.

11. Results
• AED discontinuation doubles the risk of seizures for up to 2 years
after stopping AED compared to continued treatment.
• By 2 years after randomization, 78% of patients in whom treatment
was continued and 59% of those in whom it was withdrawn
remained seizure free.
• Thereafter the differences between the two groups diminished.
• This suggests that the long-term seizure outcome is not affected
by drug discontinuation.

13. Factors predicting relapse of epilepsy
• Polytherapy (2 or more AEDs).
• Shorter prior seizure-free periods
• Primary or secondary generalised seizures.
• Myoclonic seizures
• History of neonatal seizures.
• Seizures while on AED therapy.
• Duration of AED therapy.
‘Symptomatic epilepsy was not identified as a predictive factor’

14. BMJ 1993; 306: 1374-8
• The following factors are were used to calculate seizure recurrence:
1. AED withdrawal or not.
2. Seizure free period.
3. AED polytherapy (2 or more AEDs).
4. Seizures after starting AEDs
5. Age 16 or older at the time of withdrawal
6. Myoclonic seizures
7. Primary or secondary generalised seizures.
8. Abnormal EEG.
‘Symptomatic epilepsy was not identified as a predictive factor’

16. Prospective, randomized controlled, double-blind design. Patients came for five
visits over a 12-month period, or until seizure relapse

17. Inclusion criteria Exclusion criteria
Epilepsy (2 or more unprovoked seizures) JME
Age 18-67 years Polytherapy
AED Monotherapy Pregnant or planning pregnancy
2 years seizure freedom or longer. 67% of
patients were seizure free for 5 years.
Two prior withdrawal attempts
If prior withdrawal attempted and
unsuccessful, five years seizure freedom or
longer.
Paroxysmal epileptiform discharges in primary
generalised epilepsy
Mental retardation
Progressive neurological disease
Other serious disease which may influence the
health status of the patient in the study period
Comedication (except postmenopausal hormone
substitution, hormonal contraceptives, acetylic
acid, antihypertensives and thyroxin)
150 patients were included in the intervention part of the study:
78 in the non-withdrawal and 72 in the withdrawal group.

18. Results
• 15% of patients randomized to treatment withdrawal and 7% of
those randomized to remain on treatment had a recurrence at 12
months (nonsignificant).
• Recurrence rates were 27% after a median of 41 months off
medication (open follow up).
• Those who stopped AEDs improved significantly in their
neuropsychological performance.
• Withdrawal did however not affect general health measured as
quality of life and the EEG findings.

19. Results
• Neither patient age, gender, age of epilepsy onset, partial versus
generalized epilepsy, MRI-findings, nor duration of seizure
freedom predicted seizure freedom after AED withdrawal.
• At a median of 41 months, patients on CBZ had a 3-fold chance of
remaining seizure-free after withdrawal, compared to other AEDS.
• A normal neurological examination was also a significant predictor
(multivariate analysis) for seizure freedom at 12 months.
• Well selected, low risk patients may have a 1 year recurrence rate of
only 15%.

21. Risk factors for seizure recurrence
1. History of status epilepticus
2. Poor seizure control during treatment
3. Neuroimaging evidence of perilesional gliosis
4. Hippocampal sclerosis
5. Calcified lesions.
6. Persistence of paroxysmal activity in the EEG.
Bustos JA, et al. Expert Rev Neurother 2016; 16: 1079-85.

22. • 71 patients: 46 patients (65%) decided to withdraw AEDs and 25 patients (35%)
continued AEDs.
• 12/46 (26%) who withdrew AED had seizure recurrence in 2.2 years follow up.
• 7 of these patients had tumor recurrence.

23. Inclusion criteria
• The inclusion criteria were as follows;
• Adults > 18 years of age
• Histologically confirmed WHO grade II–III glioma
• Clinically and radiologically stable disease for at least 12 months.
• Seizure freedom for at least 12 months from the date of last
surgery, irradiation or chemotherapy cycle, or
• Seizure freedom for at least 24 months from the last seizure when
a seizure occurred after the last antitumor treatment.
2/25 (8%) patients who continued AEDs had seizure recurrence during follow
up of 1.7 years. One of them had tumor progression.

26. Should we consider withholding treatment in patients with an
abnormal EEG at time of discontinuation?
• A patient with abnormal EEG (with or without epileptiform
activity, specific EEG patterns) at the time of treatment
discontinuation should be informed of an increased risk of
relapse.
• Need not continue AEDs if this is the only negative prognostic
predictor.
• The decision to stop treatment should be considered in the light of
social and personal complications of a seizure relapse [Strength of
recommendation: B].

27. Should we consider withholding treatment in patients with a
documented etiology of epilepsy (including mental retardation and
perinatal insults)?
• Such patients should be informed of an increased risk of relapse
but need not continue treatment if this is the only negative
prognostic predictor.
• This also applies to the presence of mental retardation and/or
abnormal neurologic or imaging findings.
• The decision to stop treatment should be considered in the light of
the social and personal complications of a seizure relapse.
• However, a patient with an abnormal EEG and a documented
etiology should be advised not to discontinue AEDs. (strength of
recommendation B)

28. Should we consider withholding treatment in
patients with partial seizures?
• The presence of partial seizures should not be considered per se a
reason for continuing treatment in a patient who is seizure free and
does not have other relevant predictors of relapse.
Should we consider treatment withdrawal only in patients with lower
seizure frequency before entering remission and/ or shorter
duration of active epilepsy and/or less difficult seizure control?
• Prolonged duration of active disease before and during treatment
and high seizure frequency should not be a contraindication to
treatment discontinuation [Strength of recommendation: C].

29. Prognosis of seizures after
recurrence
Likelihood of remission
Risk of refractoriness

30. • 245 of the 510 patients randomized to slow discontinuation (48%) experienced
seizures during 5 year follow-up, as compared with 164 of 503 of those allocated to
continue treatment (33%).
• Total of 409 patients post randomization seizures were studied.

31. Results
• By 3 years after a seizure, 95% of patients experienced a further 1-year
remission.
• By 5 years 90% of patients have experienced a further 2-year remission.
• The most important factors contributing to the risk of further seizures after a
first seizure after randomization were:
1. Previous seizure-free interval,
2. Having partial seizures at recurrence,
3. Having previously experienced seizures while on AEDs.

32. Study of 148 children with incident epilepsy followed up for upto 37 years.

33. 24 of 25 patients who received no AEDs after relapse with one or several seizures
regained 5-year terminal remission (5YTR), but after an average of 8.2 years.

34. Results
• 33/90 (37%) patients who stopped AEDs relapsed.
• Average follow-up after AED withdrawal was 32 ± 8.7 years.
• Relapse occurred within the first year in 36%, within the first 2
years in 46%, and within the first 3 years in 67%.
• Treatment duration prior to withdrawal was shorter in patients who
relapsed than in those who did not (5.1 ± 6.2, vs 9.2 ± 9.0,
P=0.0284).

35. Conclusion
• AED withdrawal exposes patients who were seizure-free to a transient
two-fold risk of seizures for the first 2 years after stopping AEDs.
• Seizures do not recur in most (70%) of individuals on stopping AEDs.
• Majority who relapse have no complications and will eventually become
seizure-free again.
• Symptomatic epilepsy patients with low risk have similar relapse and
subsequent remission rates as compared to other epilepsy patients.
• Cautious AED withdrawal can be offered to patients with symptomatic
epilepsy with low risk of relapse (no mental retardation, or abnormal
EEG).

36. THANK YOU