Kelsey K. Wiggs, Zheng Chang, Patrick D. Quinn, Kwan Hur, Robert Gibbons, David Dunn, Isabell Brikell, Henrik Larsson and Brian M. D'Onofrio. Attention-deficit/hyperactivity disorder medication and seizures. Neurology. In press.
Objective Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures.
Methods We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication.
Results Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24–2.42 males; OR = 2.31, 95% CI = 2.22–2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60–0.85) and without (OR = 0.71, 95% CI = 0.62–0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59–1.30) and without (OR = 1.01, 95% CI = 0.80–1.28) a seizure history.
Conclusions Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.
"There have been concerns about whether doctors could prescribe ADHD medications, which are primarily stimulants, to patients with a history of seizures," D'Onofrio told MedPage Today. "We found that those medications are not associated with increased risk of seizures, especially when looking at individuals when they are on and off their ADHD medication.
"Our findings suggest that doctors may want to consider prescribing stimulant medications for patients who have a seizure history and are struggling with impulsivity and inattention."
The concern about methylphenidate and epilepsy "arises from the Food and Drug Administration-approved methylphenidate package insert describing a risk of provoking seizures, although a literature review only yields support from an animal study, case reports, and a study of seizures after methylphenidate overdose," noted John W. Miller, MD, of the University of Washington in Seattle, writing in an accompanying published comment.
Long-term within-individual comparisons also suggested no association between medication use and seizures among individuals with (OR 0.87, 95% CI 0.59–1.30) and without (OR 1.01, 95% CI 0.80–1.28) prior seizures.
There are several possible explanations for these finding, the researchers speculated. For example, ADHD medication may treat symptoms of a shared mechanism that puts individuals at risk of both ADHD and seizures. ADHD drugs also may help patients better comply with taking anti-epileptic drugs or might reduce stress….
"While overall evidence does not support an increased risk of seizures with ADHD medication, a randomized controlled study is the best way to address this issue," wrote Miller.
He added that a previous randomized controlled study of methylphenidate showed improved attention without seizures: "While this was a single-dose study only designed to study cognition, it illustrates the path to a definitive study of ADHD medication and seizures."