In addition to the above evidence, clinical stud-ies on polytherapy are informative when considering
using a combination of AEDs. One study on 47 patients
with cognitive impairment showed that seizures were
controlled more effectively by a combination of Phe-nobarbital and Phenytoin or Phenobarbital and Car-bamazepine, than by Phenytoin and Carbamazepine
combination.
34
This suggested that a combination of
two sodium-channel blocking AEDs does not improve
seizure control significantly. Other studies indicate
that a combination of Carbamazepine and Valproate
or Carbamazepine and Vigabatrin is more effective in
seizure control than a combination of Carbamazepine
and Phenytoin, although these studies were not con-trolled for drug concentration.
35,36
The AED combina-tion for which there is the most convincing evidence
is Lamotrigine and Valproate. A large study aiming to
assess the efficacy of Lamotrigine monotherapy also
evaluated the effect on seizure control whilst taking
Lamotrigine as add-on to the first AED (Carbam-azepine, Phenytoin or Valproate). This study showed
that patients who were taking Lamotrigine and Val-proate experienced an 83% reduction in seizures,
whilst those taking the Lamotrigine and Carbam-azepine or Lamotrigine and Phenytoin combinations
experienced only a 43% and 34% reduction in sei-zures, respectively.
37
These findings should be inter-preted with some caution, however, as different doses
of Lamotrigine were used in each combination