Lamotrigine (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.
S19385
R82314
Honybun (Lamotrigine) (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) 2.39 [0.78;7.32] -/23   -/19 - 23
ref
S19394
R82400
Li (Lamotrigine) (Epilepsy), 2026 Verbal domain - The Differential Ability Scales–2nd Edition (DAS-II) - At 6 years old during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 0.51 [0.30;0.89] -/90   -/79 - 90
ref
S19371
R82154
Straub (Lamotrigine) (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 1.04 [0.86;1.26] 175/3,273   456/8,887 631 3,273
ref
S19332
R82035
Moore (Lamotrigine) (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 1.63 [1.37;1.95] C 172/934   1,134/9,335 1,306 934
ref
S15218
R62400
Bromley (Lamotrigine) (Epilepsy), 2023 Language mean score ≤ 86 (below average performance of the cohort mean) - Bayley Scales of Infant and Toddler Development - At 24 months of age during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.87 [0.19;4.07] C 4/73   3/48 7 73
ref
S8978
R30441
Coste (Lamotrigine) (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 1.20 [1.00;1.40] 149/2,813   71,832/1,707,707 71,981 2,813
ref
S8947
R30244
Husebye (Lamotrigine) (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 1.20 [0.60;2.60]
excluded (control group)
9/41   8,250/42,550 8,259 41
ref
S8949
R30249
Husebye (Lamotrigine) (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 0.92 [0.40;2.12] C 9/41   35/150 44 41
ref
S8941
R30226
Cohen-Israel (Lamotrigine), 2018 Speech delay (a majority between 6-12 years old) 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.35 [0.13;0.96] C 6/83   15/83 21 83
ref
S8950
R30251
Kasradze (Lamotrigine), 2017 Verbal comprehension (VCI) (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Matched 22.98 [2.54;207.85] -/3   -/50 - 3
ref
S9947
R35775
Videman (Lamotrigine), 2016 Griffiths Mental Developmental Scale - Hearing and speech (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 2.39 [0.62;9.19] -/8   -/59 - 8
ref
S8929
R30171
Baker (Lamotrigine) (Controls unexposed, disease free), 2015 Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No extrapolated (cont. endpoint) 1.82 [0.90;3.68]
excluded (control group)
-/29   -/210 - 29
ref
S8930
R30176
Baker (Lamotrigine) (Controls unexposed, sick), 2015 Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.00 [0.38;2.64] -/29   -/25 - 29
ref
S8952
R30278
Rihtman (Lamotrigine), 2013 Stanford Binet Intelligence Scales, Fifth Edition (SB5) - Verbal IQ (VIQ) (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 1.42 [0.67;2.98] -/41   -/52 - 41
ref
Total 12 studies 1.14 [0.87;1.48] 73,990 7,411
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 (Lamotrigine) (Epilepsy), 2026Honybun, 2026 1 2.39[0.78; 7.32]-234%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Li (Lamotrigine) (Epilepsy), 2026Li, 2026 2 0.51[0.30; 0.89]-9011%ROB confusion: criticalROB selection: lowROB classification: unclearROB missing: moderateROB mesure: lowROB reporting: low Straub (Lamotrigine) (Epilepsy), 2026Straub, 2026 3 1.04[0.86; 1.26]6313,27317%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Moore (Lamotrigine) (Indication NOS), 2025Moore, 2025 4 1.63[1.37; 1.95]1,30693418%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Bromley (Lamotrigine) (Epilepsy), 2023Bromley, 2023 5 0.87[0.19; 4.07]7733%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Coste, 2020 6 1.20[1.00; 1.40]71,9812,81318%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Husebye (Lamotrigine) (Controls unexposed, sick), 2020Husebye, 2020 7 0.92[0.40; 2.12]44417%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Cohen-Israel (Lamotrigine), 2018Cohen-Israel, 2018 8 0.35[0.13; 0.96]21835%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Kasradze (Lamotrigine), 2017Kasradze, 2017 9 22.98[2.54; 207.85]-31%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Videman (Lamotrigine), 2016Videman, 2016 10 2.39[0.62; 9.19]-83%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Baker (Lamotrigine) (Controls unexposed, sick), 2015Baker, 2015 11 1.00[0.38; 2.64]-295%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 12 1.42[0.67; 2.98]-418%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (12 studies) I2 = 72% 1.14[0.87; 1.48]73,9907,4110.250.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Epilepsy; 2: Lamotrigine) (Epilepsy; 3: Lamotrigine) (Epilepsy; 4: Lamotrigine) (Indication NOS; 5: Lamotrigine) (Epilepsy; 6: Lamotrigine) (Controls unexposed NOS) (Mixed indications; 7: Lamotrigine) (Controls unexposed, sick; 8: Lamotrigine; 9: Lamotrigine; 10: Lamotrigine; 11: Lamotrigine) (Controls unexposed, sick; 12: Lamotrigine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.87; 1.48]73,9907,41172%NAHonybun (Lamotrigine) (Epilepsy), 2026 Li (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Bromley (Lamotrigine) (Epilepsy), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 12 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.15[0.77; 1.72]73,3083,97282%NALi (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Rihtman (Lamotrigine), 2013 7 unexposed, sickunexposed, sick 1.05[0.88; 1.26]6823,4390%NAHonybun (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Bromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Baker (Lamotrigine) (Controls unexposed, sick), 2015 5 Tags Adjustment   - No  - No 1.34[0.86; 2.08]1,3781,23556%NAHonybun (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Bromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 9   - Yes  - Yes 0.96[0.71; 1.31]72,6126,17678%NALi (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.57[0.72; 3.40]-19473%NAHonybun (Lamotrigine) (Epilepsy), 2026 Li (Lamotrigine) (Epilepsy), 2026 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 6 MatchedMatched 1.70[0.38; 7.63]1,3271,02086%NAMoore (Lamotrigine) (Indication NOS), 2025 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 3 All studiesAll studies 1.14[0.87; 1.48]73,9907,41172%NAHonybun (Lamotrigine) (Epilepsy), 2026 Li (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Bromley (Lamotrigine) (Epilepsy), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 120.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.81.3480.000Honybun (Lamotrigine) (Epilepsy), 2026Li (Lamotrigine) (Epilepsy), 2026Straub (Lamotrigine) (Epilepsy), 2026Moore (Lamotrigine) (Indication NOS), 2025Bromley (Lamotrigine) (Epilepsy), 2023Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Husebye (Lamotrigine) (Controls unexposed, sick), 2020Cohen-Israel (Lamotrigine), 2018Kasradze (Lamotrigine), 2017Videman (Lamotrigine), 2016Baker (Lamotrigine) (Controls unexposed, sick), 2015Rihtman (Lamotrigine), 2013

Asymetry test p-value = 0.8222 (by Egger's regression)

slope=0.2344 (0.1433); intercept=-0.1921 (0.8325); t=0.2307; p=0.8222

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8929, 8947

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.22[0.87; 1.70]81,5674,04276%NALi (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, disease free), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, disease free), 2015 Rihtman (Lamotrigine), 2013 9 unexposed, sick controlsunexposed, sick controls 1.05[0.88; 1.26]6823,4390%NAHonybun (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Bromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Baker (Lamotrigine) (Controls unexposed, sick), 2015 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Language delay)Veroniki b (NMA) (Language delay) 4.36[0.68; 25.41]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Peron (Epilepsy) (Language disorders or delay)Peron (Epilepsy) (Language disorders or delay) 1.16[0.67; 2.00]58%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT7 metaPregmetaPreg 1.14[0.87; 1.48]72%7,411----Honybun (Lamotrigine) (Epilepsy), 2026 Li (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 Moore (Lamotrigine) (Indication NOS), 2025 Bromley (Lamotrigine) (Epilepsy), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 120.510.01.0