Topiramate (Epilepsy) updated on 04-22-2025

Cognitive developmental disorders/delay (> 6 years old)

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S19436
R82831		 Honybun (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Full-Scale (Continuous _ Mean SD) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 3.69 [0.96;14.14]
excluded (control group) 		-/11   -/23 - 11
ref
S19440
R82871		 Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Full-Scale (Continuous _ Mean SD) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 8.75 [2.01;38.04] -/11   -/19 - 11
ref
S17437
R73277		 Madley-Dowd_SE (Topiramate) (Controls exposed to LTG), 2024 Intellectual disability (intelligence quotient below 70) - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 5.23 [1.98;13.81] C
excluded (control group) 		5/71   34/2,383 39 71
ref
S17438
R73272		 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Intellectual disability (intelligence quotient below 70) - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Partial overlapping 5.73 [2.31;14.21] 5/71   194/10,769 199 71
ref
S15875
R65449		 Dreier (Topiramate) (Epilepsy) (Controls exposed to LTG), 2023 Intellectual disability - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 2.71 [1.05;6.98] C
excluded (control group) 		5/290   34/5,288 39 290
ref
S15876
R65458		 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Intellectual disability - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: Yes 2.23 [0.90;5.50] 5/290   184/22,203 189 290
ref
S7307
R53763		 Bromley (Topiramate), 2016 Full-scale IQ <85 (Wechsler Preschool and Primary Scale of Intelligence (WPPSI) / Wechsler Intelligence Scale for Children (WISC)) (5-9 years old) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No 2.17 [0.41;11.53] C 3/27   3/55 6 27
ref
Total 4 studies 3.87 [2.04;7.37] 394 399
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Honybun, 2026 1 8.75[2.01; 38.04]-1116%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 2 5.73[2.31; 14.21]1997135%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 3 2.23[0.90; 5.50]18929035%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bromley (Topiramate), 2016Bromley, 2016 4 2.17[0.41; 11.53]62713%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 21% 3.87[2.04; 7.37]3943990.920.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Topiramate) (Epilepsy; 2: Topiramate) (Controls unexposed, sick; 3: Topiramate) (Epilepsy) (Controls unexposed, sick; 4: Topiramate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.87[2.04; 7.37]39439921%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 4 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 3.87[2.04; 7.37]39439921%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 4 Tags Adjustment   - No  - No 4.62[1.18; 18.05]63834%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Bromley (Topiramate), 2016 2   - Yes  - Yes 3.57[1.42; 9.01]38836152%NAMadley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 8.75[2.01; 38.07]-11 -NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 1 Partial overlappingPartial overlapping 5.73[2.31; 14.21]19971 -NAMadley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 1 All studiesAll studies 3.87[2.04; 7.37]39439921%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 40.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.63.41.0240.000Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023Bromley (Topiramate), 2016

Asymetry test p-value = NaN (by Egger's regression)

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 15875, 17437, 19436

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 3.87[2.04; 7.37]39439921%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.73[2.04; 6.82]783720%NAHonybun (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls exposed to LTG), 2024 Dreier (Topiramate) (Epilepsy) (Controls exposed to LTG), 2023 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Cognitive developmental delay)Veroniki b (NMA) (Cognitive developmental delay) 3.06[0.42; 17.51]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 3.87[2.04; 7.37]21%399----Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024 Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 40.510.01.0