Does treatment with methylphenidate increase the risk for seizures?/nTreatment with methylphenidate

Fråga: Does treatment with methylphenidate increase the risk for seizures? Treatment with methylphenidate is being considered in a child with epilepsy and Tourette´s syndrome.

Sammanfattning: Prospective and retrospective studies provide evidence that methylphenidate is safe in patients with epilepsy or other seizure activity when good seizure control has been achieved with anticonvulsive drugs. However, this may not be true in patients with poor seizure control.

Svar: Central stimulants, such as methylphenidate, are currently the best documented drugs to treat childhood attention deficient hyperactivity disorder (ADHD) (1). We have found three studies that address the effect of methylphenidate on seizure control in patients with epilepsy. The first study included 30 children with dual diagnosis of epilepsy and attention deficient hyperactivity disorder in a 4-month follow-up study (2). The children received antiepileptic treatment only during the first 2 months, after which methylphenidate 0.3 mg/kg was added. None of the 25 children who were seizure free had attacks while taking methylphenidate. Of the five children with seizures, three had increased and two no change or reduction in seizure frequency during methylphenidate. The authors conclude that methylphenidate is safe in children who are seizure free, but caution is warranted in children with poor seizure control.

A retrospective analysis of 30 patients with traumatic head injury and subsequent active seizure disorder as well as various behavioral problems compared the seizure frequency in three months before and after introduction of methylphenidate treatment (3). Overall findings indicated a lower incidence of seizures during methylphenidate treatment. Four patients had increased seizure frequency, of which three received tricyclic antidepressants. The authors conclude that methylphenidate may be safely used in patients with traumatic head injury with active seizure disorder. The lower seizure frequency discovered during the periods of methylphenidate treatment may also be a result of spontaneous healing of the head injury after the trauma.

The last study assessed the safety of methylphenidate in children with seizures and attention deficient hyperactivity disorder (4). Ten children without seizures while receiving antiepileptic therapy were evaluated in a double-blind placebo-controlled cross-over trial for the effect of methylphenidate treatment on the seizure activity. No child had seizures during the antiepileptic-placebo phase or the antiepileptic-methylphenidate phase. Also, no changes were noted in the epileptiform features or background activity on electroencephalograms and no alternations in antiepileptic drug levels. The authors conclude that methylphenidate may be safe in the treatment of children with concurrent attention deficient hyperactivity disorder and seizures.

The Swedish national pharmacovigilance unit has not received any reports on seizures associated with methylphenidate (5). The WHO global pharmacovigilance unit has received 45 reports on convulsions associated with methylphenidate, but the causality in these cases is unclear (6). The fact that methylphenidate is used widely in epilepsy patients may alone explain this association. In fact, results from one study suggest that epilepsy may predispose children attention problems (7).