Page 425 - ILAE_Lectures_2015

Which AED?

Phenytoin is the AED still used by many geriatricians as first-line treatment. Its advantages
include once-daily dosing, low cost and ready availability in parenteral form. Disadvantages,
however, outweigh advantages and these include non-linear kinetics, such that small
alterations of dosage may produce plasma concentrations associated with toxicity or
inefficacy. Increased free concentration of phenytoin with neurotoxicity may occur when
plasma albumin falls, particularly during acute illness. As in younger people, seizure control
is frequently achieved in people with plasma concentrations below the quoted range.
Concentration-dependent neurotoxicity may be experienced more frequently and at more
modest plasma concentrations in older people. Phenytoin may cause metabolic bone disease
and folate deficiency that may be particularly problematic in this age group.

Carbamazepine, an enzyme inducer is an option in the treatment of epilepsy in the older
person particularly if there is no associated co-morbidity. Sedative effects may limit
tolerability but can be minimised by starting with a very low dose and slow upward titration.
Intra-dosage variation in concentrations of carbamazepine, which are related to the extent of
autoinduction of metabolism2123, appears to be rather less in the frail elderly. Once or twice-
daily dosing with conventional carbamazepine tablets is sufficient for most. While the overall
risk of bone marrow suppression and hepatitis is small the incidence may be increased by
age. Carbamazepine has an antidiuretic hormone-like effect, and this may produce fluid
retention and precipitate cardiac failure. Mild hyponatraemia is usually asymptomatic but
profound reductions in serum sodium may occur during intercurrent illness or during
concomitant treatment with thiazide diuretics. Carbamazepine may precipitate problems with
cardiac conduction in elderly people with pre-existent cardiac disease. There are also
concerns about its potential effects on bone health. Oxcarbazepine, a carbamazepine like pro-
drug that avoids epoxidation would be an alternative but there is no definitive data regarding
its use in this age group and there are concerns particularly with its propensity to cause
hyponatraemia.

Sodium valproate is usually very well-tolerated and effective in older people. Unlike
phenytoin and carbamazepine it is not an enzyme-inducing drug and is less susceptible to
involvement in drug interactions. Sedation, cognitive slowing, tremor and gastrointestinal
disturbances are the most frequent limiting adverse effects. Cognitive slowing usually
improves on dose reduction but it can be so severe in some older people that the drug may
have to be withdrawn.

Lamotrigine is a first-line drug in this age group particularly in view of its overall good
tolerability. It does not exhibit auto-induction, is not an enzyme inducer and has little
cognitive effect. It does, however, have the potential to cause idiosyncratic skin reactions
and, very occasionally, more severe reactions. Another problem in this age group is its
propensity to cause insomnia and tremor. If insomnia becomes a problem switching drug
intake to an earlier time may be helpful.

Levetiracetam is also a first-line drug in this age group, particularly in view of its overall
good tolerability and clean pharmacokinetic profile. It has, however, the potential to cause
lethargy and irritability which may be more pronounced in some older people.

Overall, the current treatment choice for chronic treatment of older people with epilepsy
probably rests with low-dose monotherapy with lamotrigine, levetiracetam or sodium
valproate. Phenytoin is cheap and can be given once a day in standard formulation, it is
difficult to use because of non-linear kinetics. Adverse effects of unsteadiness and dizziness
can occur even at low serum concentrations. In addition, there are concerns about its chronic