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3. Is the wrong AED for the seizure type being prescribed?
4. Has a progressive underlying condition, e.g. glioma, been missed?
5. Is there undeclared use of alcohol or drugs?

If these can be excluded the dose of the first AED needs to be increased to the level that
individual can tolerate and, if the seizures continue, the dose is then usually reduced a little
before a second AED is introduced and the dose titrated up. If the second AED is effective
then the original AED can gradually be withdrawn. It is good practice to change only one
AED at a time so that, if for example seizures increase or worsen, the cause is clearer. Which
AED should be added if the first fails is difficult to proscribe, but it would seem reasonable
to choose an AED with a different mechanism of action from the first. Theories of ‘rational
polytherapy’ are not supported by extensive evidence18, but it is recognised that the use of
drugs with similar mechanisms of action, e.g. sodium channel blockers, can be associated
with more side effects if used in high dose together.

Prognosis

The outcome for many patients starting AEDs is good, with 70% entering a prolonged
remission. Structural abnormalities, frequency of seizures and learning difficulties are
associated with poorer outcomes19. Whether treatment alters the long-term outcome is
uncertain, but studies from developing countries where the treatment gap is very wide (up to
85% not receiving medication)20 suggest that the underlying nature of the epilepsy is more
important and AEDs prevent seizures but do not alter outcome.

References

1. CHADWICK, D., REYNOLDS, E.H. When do epileptic patients need treatment? Starting and stopping
medication. Br Med J (Clin Res Ed) 1985; 290(6485): 18858.

2. FISHER, R.S., ACEVEDO, C., ARZIMANOGLOU, A. et al. A practical clinical definition of epilepsy.
Epilepsia 2014; 55(4): 475–482.

3. MARSON, A., JACOBY, A., JOHNSON, A., KIM, L. GAMBLE, C., CHADWICK, D. Immediate versus
deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial.
Lancet 2005; 365(9476): 200713.

4. HART, Y.M., SANDER, J.W., JOHNSON, A.L., SHORVON, S.D. National General Practice Study of
Epilepsy: recurrence after a first seizure. Lancet 1990; 336(8726): 12714.

5. KIM, L.G., JOHNSON, T.L., MARSON, A.G., CHADWICK, D.W. Prediction of risk of seizure recurrence
after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol 2006; 5(4):
31722.

6. SCHIERHOUT, G., ROBERTS, I. Anti-epileptic drugs for preventing seizures following acute traumatic
brain injury. Cochrane Database Syst Rev 2000(2): CD000173.

7. KWAN, P., BRODIE, M.J. Early identification of refractory epilepsy. N Engl J Med 2000; 342(5): 3149.
8. MARSON, A.G., AL-KHARUS, A.M., ALWAIDH, M. et al. The SANAD study of effectiveness of

carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an
unblinded randomised controlled trial. Lancet 2007; 369(9566): 100015.
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valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised
controlled trial. Lancet 2007; 369(9566): 101626.
10. PERSSON, L.I., BEN-MENACHEM, E., BENGTSSON, E., HEINONEN, E. Differences in side effects
between a conventional carbamazepine preparation and a slow-release preparation of carbamazepine.
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11. SABERS, A., BUCHHOLT, J.M., ULDALL, P., HANSEN, E.L. Lamotrigine plasma levels reduced by oral
contraceptives. Epilepsy Res 2001; 47(1-2): 1514.
12. PENNELL, P.B., NEWPORT, D.J., STOWE, Z.N., HELMERS, S.L., MONTGOMERY, J.Q., HENRY, T.R.
The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology 2004; 62(2): 2925.
13. MORROW, J.I., RUSSELL, A., GUTHRIE, E. et al. Malformation risks of anti-epileptic drugs in pregnancy:
A prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 2006;
77(2): 1938.
14. VAJDA, F.J., O'BRIEN, T.J., HITCHCOCK, A. et al. Critical relationship between sodium valproate dose
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15. BERKOVIC, S.F., KNOWLTON, R.C., LEROY, R.F., SCHIEMANN, J., FALTER, U. Placebo-controlled
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