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March 27, 2018; 90 (13) Article

Attention-deficit/hyperactivity disorder medication and seizures

Kelsey K. Wiggs, Zheng Chang, Patrick D. Quinn, Kwan Hur, Robert Gibbons, David Dunn, Isabell Brikell, Henrik Larsson, Brian M. D'Onofrio
First published February 23, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005213
Kelsey K. Wiggs
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Zheng Chang
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Patrick D. Quinn
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Kwan Hur
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Robert Gibbons
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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David Dunn
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Isabell Brikell
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Henrik Larsson
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Brian M. D'Onofrio
From the Department of Psychological and Brain Sciences (K.K.W., P.D.Q., B.M.D.), Indiana University, Bloomington; Department of Medical Epidemiology and Biostatistics (Z.C., I.B., H.L.), Karolinska Institutet, Stockholm, Sweden; Center for Health Statistics (Z.C., P.D.Q., K.H., R.G.) and Departments of Medicine (R.G.) and Public Health Sciences (R.G.), University of Chicago, IL; Departments of Psychiatry (D.D.) and Neurology (D.D.), Indiana University School of Medicine, Indianapolis; and School of Medical Sciences (H.L.), Orebro University, Sweden.
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Citation
Attention-deficit/hyperactivity disorder medication and seizures
Kelsey K. Wiggs, Zheng Chang, Patrick D. Quinn, Kwan Hur, Robert Gibbons, David Dunn, Isabell Brikell, Henrik Larsson, Brian M. D'Onofrio
Neurology Mar 2018, 90 (13) e1104-e1110; DOI: 10.1212/WNL.0000000000005213

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Abstract

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.

Glossary

ADHD=
attention-deficit/hyperactivity disorder;
AED=
antiepileptic drug;
CI=
confidence interval;
ICD-9=
International Classification of Diseases, Ninth Revision;
OR=
odds ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • CME Course: NPub.org/cmelist

  • Received July 31, 2017.
  • Accepted in final form December 12, 2017.
  • © 2018 American Academy of Neurology
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