The anticonvulsants, also called antiepileptic drugs
(abbreviated "AEDs"), belong to a diverse group of
pharmaceuticals used in prevention of the occurrence of
epileptic
seizures. More and more, anticonvulsants are also finding ways
into the treatment of
bipolar disorder, since many seem to act as
mood stabilizers. The goal of an anticonvulsant is to suppress
the rapid and excessive firing of
eurons
that start a seizure. Failing this, a good anticonvulsant would
prevent the spread of the seizure within the brain and offer
protection against possible
excitotoxic effects that may result in
brain damage. However, anticonvulsants themselves have been
linked to lowered IQ.
The major molecular targets of marketed anticonvulsant drugs are
voltage-gated sodium channels; components of the
GABA system, including GABAA receptors, the GAT-1 GABA
transporter, and
GABA transaminase; and voltage-gated
calcium channels.
Some anticonvulsants have shown antiepileptogenic effects in animal
models of epilepsy. That is, they either prevent the expected development of
epilepsy or can halt or reverse the progression of epilepsy. However, no
drug has shown this effect in human trials.
The usual method of achieving approval for a drug is to show it is effective
when compared against placebo, or that it is more effective than an existing
drug. In monotherapy (where only one drug is taken) it is considered unethical
by most to conduct a trial with placebo on a new drug of uncertain efficacy.
This is because untreated epilepsy leaves the patient at significant risk of
death. Therefore, almost all new epilepsy drugs are initially approved only as
adjunctive (add-on) therapies. Patients whose epilepsy is currently uncontrolled
by their medication (i.e., it is refractory to treatment) are selected to see if
supplementing the medication with the new drug leads to an improvement in
seizure control. Any reduction in the frequency of seizures is compared against
a placebo.
Once there is confidence that a drug is likely to be effective in monotherapy,
trials are conducted where the drug is compared to an existing standard. For
partial-onset seizures, this is typically
carbamazepine. Despite the launch of over ten drugs since 1990, no new drug
has been shown to be more effective than the older set, which includes
carbamazepine, valproate and phenytoin. The lack of superiority over existing
treatment, combined with the lack of placebo-controlled trials, means that few
modern drugs have earned FDA approval as initial monotherapy. In contrast,
Europe only requires equivalence to existing treatments, and has approved many
more. Despite their lack of FDA approval, the
American Academy of Neurology and the American Epilepsy Society still
recommend a number of these new drugs as initial monotherapy.
