Topiramate (All indications) 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.
S19392
R82384
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
S19388
R82344
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
S19379
R82266
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
S19372
R82170
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
S19337
R82023
Moore (Controls exposed to LTG) (Topiramate) (Indication NOS), 2025 Speech, language and communication disorders - Assessment offered to all children - At the 27–30 months during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.65 [0.40;1.05] C
excluded (control group)
22/172   172/934 194 172
ref
S19330
R82044
Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Speech, language and communication disorders - Assessment offered to all children - At the 27–30 months during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: No Matched 1.22 [0.76;1.95] C 22/172   185/1,720 207 172
ref
S12810
R48233
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
S12811
R48234
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
S10103
R36820
Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Visits to a speech therapist (mean age of 3.7 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.20 [0.80;1.80]
excluded (control group)
33/477   157/2,916 190 477
ref
S8613
R28742
Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Health care utilization: Speech therapy (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.40 [1.00;2.00] 33/477   72,012/1,710,441 72,045 477
ref
S8583
R28561
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
S8584
R28563
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
S8585
R28565
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
S8582
R28544
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
S8615
R28766
Rihtman (Topiramate) (Mixed indications), 2012 Verbal IQ (Stanford Binet) (mean age around 4 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 5.71 [1.23;26.53] -/9   -/18 - 9
ref
Total 8 studies 1.56 [1.02;2.37] 72,807 1,674
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]-198%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]51296126%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025Moore, 2025 3 1.22[0.76; 1.95]20717221%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: low Meador (Topiramate) (Controls unexposed, disease free), 2021Meador, 2021 4 2.49[0.48; 12.82]-55%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: low Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 5 1.40[1.00; 2.00]72,04547724%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Husebye (Topiramate) (Controls unexposed, sick), 2020Husebye, 2020 6 1.10[0.11; 10.87]3643%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Topiramate), 2016Bromley, 2016 7 1.59[0.33; 7.69]7276%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rihtman (Topiramate) (Mixed indications), 2012Rihtman, 2012 8 5.71[1.23; 26.53]-96%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 61% 1.56[1.02; 2.37]72,8071,6740.220.01.0ROB: 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: Controls unexposed, general pop) (Topiramate) (Indication NOS; 4: Topiramate) (Controls unexposed, disease free; 5: Topiramate) (Controls unexposed, NOS) (Mixed indications; 6: Topiramate) (Controls unexposed, sick; 7: Topiramate; 8: Topiramate) (Mixed indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.56[1.02; 2.37]72,8071,67461%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Meador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.48[1.02; 2.14]72,25266325%NAMoore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Meador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Rihtman (Topiramate) (Mixed indications), 2012 4 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 2.44[1.00; 5.92]25023159%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 5   - Yes  - Yes 1.16[0.76; 1.77]72,5571,44358%NAStraub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 5.20[2.26; 11.98]-330%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Meador (Topiramate) (Controls unexposed, disease free), 2021 Rihtman (Topiramate) (Mixed indications), 2012 3 MatchedMatched 2.20[0.50; 9.61]20718172%NAMoore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Rihtman (Topiramate) (Mixed indications), 2012 2 All studiesAll studies 1.56[1.02; 2.37]72,8071,67461%NAHonybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026 Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Meador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 80.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.83.21.4050.000Honybun (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Straub (Controls unexposed, sick) (Topiramate) (Epilepsy), 2026Moore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025Meador (Topiramate) (Controls unexposed, disease free), 2021Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Husebye (Topiramate) (Controls unexposed, sick), 2020Bromley (Topiramate), 2016Rihtman (Topiramate) (Mixed indications), 2012

Asymetry test p-value = 0.0694 (by Egger's regression)

slope=-0.1805 (0.2094); intercept=1.6439 (0.7449); t=2.2071; p=0.0694

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10103, 8583, 8584, 12810, 19337, 19392, 19379

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.42[1.07; 1.87]80,5036672%NAMoore (Controls unexposed, general pop) (Topiramate) (Indication NOS), 2025 Meador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, disease free), 2020 Rihtman (Topiramate) (Mixed indications), 2012 5 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 1.06[0.79; 1.43]6251,63030%NAHonybun (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Straub (Controls exposed to LTG) (Topiramate) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Topiramate) (Indication NOS), 2025 Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021 Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020 60.510.01.0