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Pharmacological interventions
The majority of data on pharmacological studies, with some notable exceptions to be
discussed later, concern add-on, open, non-randomised design, usually with the novel AEDs.
Such studies are reasonably numerous but, of course, are open to methodological criticism
and hence interpretation is difficult.

Trials using open non-controlled methodology in populations with learning disability and
refractory epilepsy have shown a 50% reduction in seizures in 33% of patients at three-month
follow up on vigabatrin29, with a reduction in this response by one-third at five-year follow-
up30.

A similar methodology using lamotrigine in a childhood population31 showed a 50%
improvement in seizure control in 74% of children, with an associated improvement in quality
of life using clinical judgement.

In addition to these studies, which have tended to investigate cohorts of individuals with
learning disability, a further fruitful area of pharmacological research has been in epilepsy
syndromes strongly associated with learning disability  West syndrome, infantile spasms,
and the Lennox-Gastaut syndrome. The former, being a developmental age-defined
syndrome, is somewhat less useful in the population we are studying, however. Chiron and
colleagues32 have shown in both open and a limited placebo-controlled run-in an impressive
efficacy for vigabatrin in this population, with 43% of children showing complete cessation
of seizures and 46 out of 70 children showing a greater than 50% reduction in seizures. In a
recent report, in abstract form, of a double-blind, placebo-controlled study of vigabatrin in
infantile spasms Appleton and Thornton33 showed a complete cessation of seizures in 45% of
the active versus 15% of the control group.

The clinical effectiveness data in Lennox-Gastaut syndrome is of particular interest to
clinicians dealing with both children and adults with learning disability. Two good quality
randomised controlled trials have been performed.

Lamotrigine has been subject to the most rigorous quality of life evaluation in the Lennox-
Gastaut population. The compound has been investigated through a randomised, placebo-
controlled, add-on design34. Importantly, however, this study used a specifically designed
quality of life scale and parental global health evaluation in addition to the usual seizure
frequency measures. In terms of seizure efficacy the study was successful with a significant
reduction in atonic seizures and in total seizures. The impact on quality of life measures was
interesting. Parent/carer assessment showed an improvement in global health. Outcome on
the ELDQOL showed significant improvement in mood and reduced seizure severity, but no
difference in side effect profile was seen when compared with placebo.

Topiramate. This study recruited 98 patients aged 242 years. Primary successful outcome
points were deemed to be either a combination of a significant reduction in atonic (drop)
attacks and parental global evaluation of seizure severity or a percent reduction of all seizure
types. It can be seen that some attempt was made to evaluate the impact on quality of life
through these parental evaluations.

The methodology applied was a randomised, placebo-controlled, add-on design. The
population had quite severe seizures with all having at least 60 seizures per month.

Results showed a statistically significant median reduction in drop attacks (placebo increased
by 5%, topiramate decreased by 15%; P = 0.04) and in parent evaluation of seizure severity
(placebo 28% improvement, topiramate 52%). There was no statistically significant decrease