Lamotrigine (Epilepsy) updated on 04-22-2025

ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk

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.
S19477
R83184		 Straub (Lamotrigine) (Epilepsy), 2026 Attention deficit hyperactivity disorder (ADHD) - ICD-10 codes: F90.x - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 1.09 [0.86;1.38] 102/3,273   366/8,887 468 3,273
ref
S17430
R73222		 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Partial overlapping 0.81 [0.66;1.00] 109/2,383   929/10,769 1,038 2,383
ref
S17251
R72260		 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median 6.18 (3.53-9.94) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 1.81 [0.92;3.58] 14/791   38/4,075 52 791
ref
S15870
R65393		 Dreier, 2023 Attention-deficit/hyperactivity disorder (ADHD) - 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 0.83 [0.66;1.04] 95/5,288   528/22,203 623 5,288
ref
S6604
R39734		 Bromley (Controls unexposed, disease free), 2013 Attention deficit hyperactivity disorder (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 7.24 [0.14;371.71] C
excluded (control group) 		0/30   0/214 0 30
ref
S6603
R39736		 Bromley (Controls unexposed, sick), 2013 Attention deficit hyperactivity disorder (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.86 [0.02;45.15] C 0/30   0/26 0 30
ref
S6295
R39719		 Rihtman, 2013 Conners’ Parent - ADHD Index (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 1.21 [0.57;2.56] -/39   -/52 - 39
ref
S6394
R39720		 Veiby (Controls unexposed, disease free) b, 2013 ADHD symptoms ≥ 2SD (at 36 months) (Specific checklist) (Parent-reported) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 1.50 [0.40;4.80]
excluded (control group) 		3/44   1,743/43,571 1,746 44
ref
S6393
R39721		 Veiby (Controls unexposed, sick) b, 2013 ADHD symptoms ≥ 2SD (at 36 months) (Specific checklist) (Parent-reported) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.74 [0.59;12.75] C 3/44   4/154 7 44
ref
Total 7 studies 0.98 [0.80;1.20] 2,188 11,848
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 Straub (Lamotrigine) (Epilepsy), 2026Straub, 2026 1 1.09[0.86; 1.38]4683,27327%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 2 0.81[0.66; 1.00]1,0382,38329%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Madley-Dowd_UK, 2024 3 1.81[0.92; 3.58]527917%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Dreier, 2023Dreier, 2023 0.83[0.66; 1.04]6235,28828%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bromley (Controls unexposed, sick), 2013Bromley, 2013 4 0.86[0.02; 45.15]0300%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman, 2013Rihtman, 2013 1.21[0.57; 2.56]-396%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Veiby (Controls unexposed, sick) b, 2013Veiby, 2013 5 2.74[0.59; 12.75]7442%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 43% 0.98[0.80; 1.20]2,18811,8480.210.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Epilepsy; 2: Lamotrigine) (Controls unexposed, sick; 3: Lamotrigine) (Epilepsy; 4: Controls unexposed, sick; 5: Controls unexposed, sick) ;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.98[0.80; 1.20]2,18811,84843%NAStraub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Veiby (Controls unexposed, sick) b, 2013 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.21[0.57; 2.56]-39 -NARihtman, 2013 1 unexposed, sickunexposed, sick 0.97[0.78; 1.22]2,18811,80950%NAStraub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bromley (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 6 Tags Adjustment   - No  - No 1.40[0.72; 2.72]71130%NABromley (Controls unexposed, sick), 2013 Rihtman, 2013 Veiby (Controls unexposed, sick) b, 2013 3   - Yes  - Yes 0.96[0.76; 1.20]2,18111,73563%NAStraub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.21[0.57; 2.56]-39 -NARihtman, 2013 1 Partial overlappingPartial overlapping 0.81[0.66; 1.00]1,0382,383 -NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 1 All studiesAll studies 0.98[0.80; 1.20]2,18811,84843%NAStraub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Veiby (Controls unexposed, sick) b, 2013 70.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.72.4220.000Straub (Lamotrigine) (Epilepsy), 2026Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Dreier, 2023Bromley (Controls unexposed, sick), 2013Rihtman, 2013Veiby (Controls unexposed, sick) b, 2013

Asymetry test p-value = 0.1474 (by Egger's regression)

slope=-0.2447 (0.1226); intercept=1.2529 (0.7314); t=1.7129; p=0.1474

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6604, 6394

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.34[0.71; 2.53]1,7461130%NABromley (Controls unexposed, disease free), 2013 Rihtman, 2013 Veiby (Controls unexposed, disease free) b, 2013 3 unexposed, sick controlsunexposed, sick controls 0.97[0.78; 1.22]2,18811,80950%NAStraub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bromley (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 60.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Peron (Epilepsy) (Diagnosis or risk of ADHD)Peron (Epilepsy) (Diagnosis or risk of ADHD) 1.14[0.75; 1.72]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 0.98[0.80; 1.20]43%11,848----Straub (Lamotrigine) (Epilepsy), 2026 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Veiby (Controls unexposed, sick) b, 2013 70.510.01.0