Abstract
Background
The prevalence of epilepsy among people with intellectual disabilities is much higher than in the general population. Seizures in this population are often complex and refractory to treatment and antiepileptic medication may have a profound effect upon behaviour (Kerr 1997).
This is an updated version of a Cochrane Review first published in Issue 3, 2007.
Objectives
To assess the data available from randomised controlled trials (RCTs) of the efficacy of antiepileptic drug (AED) interventions in people with epilepsy and intellectual disabilities.
Search methods
For the latest update of this review, we searched the Cochrane Epilepsy Group Specialised Register (2 September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO) (2 September 2014), MEDLINE (Ovid, 1946 to 3 September 2014) and PsycINFO (EBSCOhost, 1887 to 3 September 2014).
Selection criteria
Randomised and quasi-randomised controlled trials (RCTs) of pharmacological interventions for people with epilepsy and a learning disability.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We assessed epilepsy/seizure, behavioural and cognitive outcomes, as well as quality of life and adverse effects.
Main results
We included 14 RCTs (1116 participants) in the present review. Data were heterogenous and a descriptive analysis is presented. In the majority of cases where antiepileptic drugs (AEDs) were trialled in this population, we found moderate reductions in seizure frequency in that there was a significantly higher rate of responders (reduction of 50% or more) in the treatment group compared with the placebo group, with some studies reporting a higher incidence of seizure freedom in the treatment group. In general, AEDs that are proven to be effective in the general epilepsy population are also effective for refractory epilepsy in people with intellectual disability. It is not possible to comment on the relative efficacy of medications, making clinical decisions difficult.
In trial settings patients continued on treatment in the majority of cases. Placebo groups often experienced fewer adverse events. Where adverse events were experienced they appeared similar to those in the general population. The methods by which adverse events were recorded and reported appeared to be inconsistent, resulting in very large variation between studies. This is problematic as clinically relevant interpretation of these findings is limited.
The quality of evidence provided in the present review is low to moderate. Additionally the majority of studies lacked or used non-reliable measures of behavioural exacerbation. However, where measured, little obvious impact on behaviour was seen in terms of behaviour disorder.
Authors’ conclusions
This review broadly supports the use of AEDs to reduce seizure frequency in people with refractory epilepsy and intellectual disability. The evidence suggests that adverse events are similar to those in the general population and that behavioural adverse events leading to discontinuation are rare; however, other adverse effects are under-researched.
Plain language summary
Pharmacological interventions for epilepsy in people with intellectual disability
Background
Epilepsy is a common condition. Approximately 3% of the general population are diagnosed with epilepsy at some point in their life (Rugg-Gunn 2012). However, epilepsy is significantly more common in people with intellectual disabilities where estimates range from 14% to 44% (Bowley 2000). People with intellectual disability and epilepsy often do not respond as well to antiepileptic drugs (AEDs) as the general population and behavioural disturbances are frequent. We review the use of AEDs in this population.
Study characteristics
The evidence is current to 2 September 2014. The included studies assessed the effectiveness of pharmacological interventions in people with epilepsy and intellectual disability. In total we included 14 studies and data from 1116 participants in the present review update. Five studies were funded by pharmaceutical companies, seven studies had insufficient information regarding how the trial was funded and one study was free from other bias.
Key results
This updated review confirms that in the majority of cases where intellectually disabled populations participated in trials of AEDs, moderate reductions in seizure frequency and occasional seizure freedom were obtained. The present update found that participants in the AED groups were more likely to report a 50% or greater reduction in seizure frequency compared with the control groups. The results also suggested that participants in the AED group were more likely to become seizure-free and report a 50% or greater reduction in seizure frequency compared with participants in the placebo group, however these results were not significant. Additionally, the results of the present update suggest that more participants in the AED groups withdrew from treatment and reported adverse effects compared with the placebo group, however these results were also not significant. Where adverse events were reported they appeared to be similar to those seen in people without intellectual disability and thus they were not specific to this population.
In summary, this review broadly supports the use of AEDs to reduce seizure frequency in patients with refractory epilepsy and intellectual disability. Side effects seem to be the same as in people with epilepsy without intellectual disabilities and behavioural adverse events leading to withdrawal from the treatment are rare.
Quality of the evidence
The quality of evidence provided by this review is low to moderate. There is a large amount of variation across the studies in that different studies used different AEDs and reported different outcomes. Due to the inconsistencies between studies, not all studies could be included in the meta-analyses. Therefore the statistical analysis in the present update is limited.
Overall there appear to be very few high quality studies assessing pharmacological interventions for people with epilepsy and intellectual disability. We hope that further research will be conducted in this area to provide a more thorough understanding.
