Medication for attention-deficit hyperactivity disorder (ADHD) does not increase the risk for seizures in people with epilepsy, according to the results of a study published in the February issue of the journal Epilepsia.

The research used data from three Swedish registries, identifying more than 21,000 people with a history of seizures born between 1987 and 2003. From this group, researchers identified 6,774 children who met the criteria for epilepsy; of these, 1,605 were on continuous treatment with anti-epileptic drugs (AEDs) during the 8 years of follow-up.

They also identified people who were on ADHD medication (as indicated by the Swedish prescription registry) at any time during the follow-up period, which lasted from 2006 to 2013, as well as people who first started taking ADHD medication during that time.

No increased risk

Seizures were identified through hospital or specialist visits logged in the Swedish Patient Registry. By analyzing each patient’s data, the researchers showed no increased risk for seizures associated with ADHD medications. In fact, periods in which ADHD medication was prescribed were associated with a 27% reduction in seizures, compared with periods when ADHD medication was not prescribed.

“When you compare risk between individuals, there’s a lot of factors that might explain associations that have nothing to do with the medication itself,” noted Kelsey Wiggs, a PhD candidate at Indiana University, Bloomington and study author. “So it’s a good feature of this study that we were able to compare the same individual on and off the medication – we could rule out a lot of other confounders.”

Subgroup analyses also showed no association between seizure frequency and ADHD medication. In some of the analyses, ADHD medication was associated with a significantly lower risk of seizures, but it was never associated with a higher risk.

“This study provides another piece of evidence that medications for kids with ADHD do not increase the risk for seizures,” said Kimford J. Meador, professor of neurology and neurosciences at Stanford University and clinical director of the Stanford Comprehensive Epilepsy Center, who was not involved in the research. “I think that physicians should feel safe prescribing these medications within standard doses.”

Last year the journal Neurology published a similar study, in which researchers analyzed US data from more than 800,000 people. They found no evidence that taking ADHD medication increased seizure risk in people with and without epilepsy.

Treating ADHD in people with epilepsy

It’s estimated that overall, 11% of children receive an ADHD diagnosis between ages 3 and 17. ADHD is more common in people with epilepsy than in the general population: As many as 50% of children with epilepsy and 20% of adults also carry an ADHD diagnosis. Though medical treatment of ADHD is not without controversy, untreated ADHD is a risk factor for later adult mental health issues, as well as academic impairment throughout childhood.

North American and European package inserts for methylphenidate and amphetamine products warn of the drugs’ potential to lower the seizure threshold. Pre-clinical studies and reports of seizures linked with stimulant abuse or overdose may be partly responsible for the warnings; there are few empirical data on the risk of seizures at therapeutic doses, such as for treating ADHD.

“Prior to this and the Neurology study, most literature has shown a good-faith effort to study the question, but because of the rarity of seizures, it’s been difficult,” said Wiggs, who was first author of the US study.

Reassuring results

The main strength of the study was its size, noted Wiggs. “We had enough power to actually study the association,” she said. “Often when you find null results, people don’t know what to do. In a small study, of course you should temper your conclusions because you don’t know if there really is no association, or you just didn’t detect it.”

Because the Swedish research used data from registries, there were no records to confirm an epilepsy diagnosis or to provide information on epilepsy subtypes. Also, researchers had to equate ADHD medication prescriptions with medication adherence. And because a seizure was only counted if it resulted in a specialist or hospital visit, Wiggs notes that the overall seizure rates may be underestimated.

The authors also noted that because clinical guidelines caution against the use of ADHD medications in people with epilepsy, some prescriptions may have been withheld. However, the prescription rate of ADHD medication in the study (64%) fell between the Swedish rates for adult prescriptions (55%-60%) and those for children (75%).

“People with epilepsy are often denied effective treatment for their psychiatric and neuropsychiatric comorbidities out of fear that such treatment may have a negative impact on seizure control,” said Torbjorn Tomson, professor of neurology and epileptology in the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, who was not affiliated with the study. “The results should be reassuring for people with epilepsy who are in need of treatment for their ADHD.”