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Pregabalin
Pregabalin has been licensed for the adjunctive treatment of refractory focal epilepsy. People
with comorbid generalised anxiety seem to particularly benefit from it. Pregabalin is closely
related to gabapentin, it is also a structural analogue of the neurotransmitter GABA that does
not seem to affect transmitter response. It modulates calcium channels by binding to a subunit
of Ca+ and this action is thought to be the basis of its antiepileptic mechanism.

The recommended dosages are between 150 and 600 mg divided into two doses, although
some people may respond to doses outside this range. Pregabalin would normally be started
at 50 or 75 mg bid and increased in incremental steps of 50 mg every two weeks up to 600
mg according to clinical need. Pregabalin is available in 25, 50, 75, 100, 150, 200 and 300
mg tablets.

Overall pregabalin is well tolerated and so far no idiosyncratic side effects have been
described. Dizziness, drowsiness, ataxia, tremor and diplopia are the most common side
effects. Weight gain, particularly with higher doses can be a major issue for some people. No
pharmacokinetic interactions have yet been identified. In addition to its use in epilepsy,
pregabalin has also been indicated for neuropathic pain and in generalised anxiety disorders.

Stiripentol
Stiripentol is licensed as an orphan drug for Dravet’s syndrome when used in conjunction
with sodium valproate and clobazam. It is an aromatic alcohol and is unrelated to any other
AED. Its mode of action is unknown.

Retigabine
Retigabine has just been licensed as add-on for focal epilepsy. It is the first drug licensed
which acts as a modulator of potassium channels. Effective dose is likely to be somewhere
between 600 and 1200 mg a day. The commonest emerging treatment side effects are CNS-
related and drowsiness, dizziness, slurred speech, ataxia, tremor and diplopia. It also causes
urinary tract symptoms in some people. No clinically significant pharmacokinetic interaction
has yet been seen. An unexpected side effect has recently been associated with the chronic
use of retigabine and this consists of a blue skin discoloration and pigmentary changes in the
retina. The mechanism of this is unknown. It is likely that this will limit the use of the drug.

Rufinamide
Rufinamide is licensed as an orphan drug for the Lennox-Gastaut spectrum when used as an
adjunctive. It is a triazole derivative and is unrelated to any other AED. Its mode of action is
unknown.

Zonisamide
Zonisamide, a sulphonamide analogue which inhibits carbonic anhydrase, is a potent blocker
of the spread of epileptic discharges. This is believed to be mediated through action at
voltage-sensitive sodium channels. It is currently indicated for people with focal seizures with
or without secondary generalisation but it is likely to be a broad-spectrum drug. It can be
effective in generalised seizures particularly myoclonic seizures. Recommended doses are
between 200 and 500 mg/day, although some people may derive benefit from doses outside
this range. The recommended starting dose for most people is 50 mg once daily, titrating
upwards every two weeks in 50 mg/day increments until seizure control is achieved or side
effects develop. Its long elimination half-life allows once-daily dosing.

Zonisamide may increase phenytoin levels by about 1015%. Zonisamide metabolism is
induced by carbamazepine, barbiturates and phenytoin and higher doses may be necessary
during co-administration with these AEDs.