Table E-1. List of Aeds Included in Analyses As Time-Varying Covariate

Table e-1. List of AEDs included in analyses as time-varying covariate

Generic Drug Names

Antiepileptic Drugs Acetazolamide, Carbamazepine, Clobazam, Clonazepam, Diazepam, Divalproex Sodium, Eslicarbazepine, Ethosuximide, Ethotoin, Felbamate, Gabapentin, Lacosamide, Lamotrigine, Levetiracetam, Mesuximide, Oxcarbazepine, Perampanel, Phenobarbital, Phenytoin, Pregabalin, Primidone, Rufinamide, Tiagabine, Topiramate,Valproate, Vigabatrin, Zonisamide

Table e-2. Group Comparisons

ADHD Patients vs ADHD Patients Non-ADHD Controls Controls OR (95% CI) Overall N with % with Overall N with % with

N Seizures Seizures N Seizures Seizures

Male 474,742 8,725 1.84 474,742 3,793 0.80 2.33 (2.24, 2.42)

Female 327,089 6,752 2.06 327,089 2,958 0.90 2.31 (2.22, 2.42)

Medicated vs Never Medicated at Least Once Never Medicated Medicated OR (95% CI) Overall N with % with Overall N with % with

N Seizures Seizures N Seizures Seizures

Male 204,448 2,950 1.44 270,294 5,775 2.14 0.63 (0.60, 0.67)

Female 177,253 2,881 1.63 149,836 3,871 2.58 0.61 (0.57, 0.64)

ADHD medicated vs Medicated at Least Non-ADHD

Controls Once Controls OR (95% CI) Overall N with % with Overall N with % with

N Seizures Seizures N Seizures Seizures

Male 204,448 2,950 1.44 204,448 1,755 0.86 1.69 (1.59, 1.80)

Female 177,253 2,881 1.63 177,253 1,798 1.01 1.61 (1.52, 1.71)

Note. Cases were individuals from the included ADHD patient cohort who were at least 5 years old and following a period of 1 year in the data without any treatment. Controls were matched on age in years at first enrollment, sex, calendar year of first enrollment, and months of enrollment with prescription coverage. ORs reflect comparisons made on different seizure events during enrollment. ADHD = attention-deficit hyperactivity disorder. OR = odds ratio. CI = confidence interval.

Table e-3. Adjusted Concurrent Within-Individual Associations between AED Medication and Seizures

Patients Seizures Cohort (Within Only) OR (95% CI) (N) (N)

Any prior seizure 9,739 2,890 1.52 (1.39, 1.67)

Stimulant only 801,838 5,427 1.52 (1.39, 1.67)

1-month extended 801,838 5,427 1.52 (1.39, 1.67)

ER only 801,838 3,539 1.50 (1.34, 1.67)

Men only 474,744 3,105 1.53 (1.35, 1.73)

Women only 327,094 2,322 1.51 (1.31, 1.74)

Age group

5-6 81,089 873 1.97 (0.73, 1.23)

7-12 223,045 1,345 1.43 (1.18, 1.74)

13-17 130,535 1,156 1.66 (1.37, 2.01)

18-25 144,115 910 1.20 (0.97, 1.50)

26-35 78,188 396 1.66 (1.20, 2.31)

36-45 73,491 374 1.45 (1.01, 2.10)

4 6+ 71,375 373 1.31 (0.91, 3.99)

Note. Within-individual models control for time since last seizure event and ADHD prescription. AED = antiepileptic drug. ADHD = attention-deficit hyperactivity disorder. OR = odds ratio. CI = confidence interval.

Table e-4. Adjusted Long-Term Cumulative and Time Interval Within-Individual Associations between AED Medication and Seizures

Patients Seizures Cohort (Within Only) OR (95% CI) (N) (N)

Cumulative Duration

Any prior seizure 3,480 805 1.26 (0.95, 1.66)

3 years 193,612 1,246 1.44 (1.19, 1.74)

Stimulant medication only 305,327 1,981 1.54 (1.32, 1.79)

ER only 305,327 1,403 1.40 (1.74, 1.67)

Men only 184,172 1,154 1.82 (1.49, 2.22)

Women only 121,155 827 1.21 (0.95, 1.53)

Time Interval

3 years 193,612 1,246 1.45 (1.19, 1.74)

2 years 305,327 1,981 1.25 (0.95, 1.65)

Note. Adjusted models adjust for current and long-term ADHD medication status and time since last seizure event. Cumulative associations are the odds of events predicted by the cumulative number of months medicated during the two or three years prior. Interval associations are the odds of events predicted by medication status two or three years prior. AED = antiepileptic drug. ADHD = attention-deficit hyperactivity disorder. OR = odds ratio. CI = confidence interval.