Topiramate (Epilepsy) updated on 04-22-2025

Language disorders/delay

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
R82832		 Honybun (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Verbal Comprehension Index - 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) 2.43 [0.65;9.11]
excluded (control group) 		-/11   -/23 - 11
ref
S19440
R82872		 Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Verbal Comprehension Index - 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) 7.49 [2.15;26.10] -/19   -/19 - 19
ref
S19464
R82988		 Straub (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.10 [0.80;1.49] C
excluded (control group) 		56/961   175/3,273 231 961
ref
S19474
R83121		 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.89 [0.66;1.19] 56/961   456/8,887 512 961
ref
S12808
R48231		 Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: Yes extrapolated (cont. endpoint) 2.58 [0.50;13.27]
excluded (control group) 		-/5   -/93 - 5
ref
S12809
R48232		 Meador (Topiramate) (Controls unexposed, disease free), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 2.49 [0.48;12.82] -/5   -/87 - 5
ref
S7714
R22905		 Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 1.19 [0.11;12.82] C
excluded (control group) 		1/4   9/41 10 4
ref
S7703
R22883		 Husebye (Topiramate) (Controls unexposed, disease free), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: Yes 1.10 [0.10;10.90]
excluded (control group) 		1/4   8,250/42,550 8,251 4
ref
S7708
R22893		 Husebye (Topiramate) (Controls unexposed, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 1.10 [0.11;10.87] C 1/4   35/150 36 4
ref
S7307
R21178		 Bromley (Topiramate), 2016 Verbal abilities <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 1.59 [0.33;7.69] C 3/27   4/55 7 27
ref
Total 5 studies 1.90 [0.73;4.94] 555 1,016
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 7.49[2.15; 26.10]-1921%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Straub, 2026 2 0.89[0.66; 1.19]51296133%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Meador (Topiramate) (Controls unexposed, disease free), 2021Meador, 2021 3 2.49[0.48; 12.82]-517%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: low Husebye (Topiramate) (Controls unexposed, sick), 2020Husebye, 2020 4 1.10[0.11; 10.87]36411%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Topiramate), 2016Bromley, 2016 5 1.59[0.33; 7.69]72718%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 67% 1.90[0.73; 4.94]5551,0160.220.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Topiramate) (Epilepsy; 2: Controls unexposed, sick) (Topiramate) (Epilepsy; 3: Topiramate) (Controls unexposed, disease free; 4: Topiramate) (Controls unexposed, sick; 5: Topiramate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.90[0.73; 4.94]5551,01667%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.49[0.48; 12.87]-5 -NAMeador (Topiramate) (Controls unexposed, disease free), 2021 1 unexposed, sickunexposed, sick 1.82[0.58; 5.70]5551,01173%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 4 Tags Adjustment   - No  - No 2.92[0.86; 9.92]435041%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 3   - Yes  - Yes 1.07[0.49; 2.32]51296632%NAStraub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 4.94[1.74; 14.07]-249%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 2 All studiesAll studies 1.90[0.73; 4.94]5551,01667%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 50.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.83.41.4050.000Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Meador (Topiramate) (Controls unexposed, disease free), 2021Husebye (Topiramate) (Controls unexposed, sick), 2020Bromley (Topiramate), 2016

Asymetry test p-value = 0.1952 (by Egger's regression)

slope=-0.3190 (0.2960); intercept=1.5613 (0.9397); t=1.6615; p=0.1952

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7714, 7703, 12808, 19436, 19464

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.90[0.50; 7.31]8,25190%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Husebye (Topiramate) (Controls unexposed, disease free), 2020 2 unexposed, sick controlsunexposed, sick controls 1.82[0.58; 5.70]5551,01173%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.17[0.87; 1.57]2419810%NAHonybun (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Straub (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021 Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020 40.510.01.0