SIR–Santos et al.[1] convincingly demonstrate that methylphenidate (MPH) is effective in improving attention-deficit–hyperactivity disorder symptoms in children with active seizure disorders.

Among a group of 163 individuals with Dravet syndrome, a difficult-to-treat epilepsy, we recently showed that up to two-thirds of children have inattention/hyperactivity symptoms, highlighting that treatment with MPH might be a valuable contribution in their management.[2]

However, the study design of Santos et al. does not allow a conclusion that MPH improves seizure severity. The study had a 3-month baseline period without MPH followed by a 3-month trial period with MPH. Seizure frequency and severity decreased during the adjustment of antiepileptic drugs (AEDs) measured after 2 months of the baseline period. After this further adjustment of AEDs was undertaken for another month right up to the point when MPH was started. The next measurement of seizure frequency and severity was not done until 1 month into MPH treatment. It is therefore impossible to say whether the improvement in seizure frequency and severity was due to MPH treatment or AED adjustment. Table SI (online supporting information) clearly showed that in six previous studies (including a total of 174 patients) there was no MPH effect on seizures and the present study of 22 patients certainly does not refute these findings.

In addition, it remains debateable whether the individuals examined in the Santos et al. study truly had difficult-to-treat epilepsy. Inclusion criteria state that participants had ‘active epilepsy manifested by at least one seizure in the 3 months preceding inclusion on adequate doses of at least one AED judged appropriate for the epilepsy syndrome’. Table SII (online supporting information) showed that 10 out of 22 participants were on AED monotherapy at study onset and during the AED adjustment period 10 out of 22 individuals achieved complete seizure control. The term active epilepsy might be more appropriate in this context rather than difficult-to-treat epilepsies as mentioned in the title.


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