Lamotrigine (All indications) updated on 04-22-2025

Limb defects

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.
S19361
R82069		 Seo (Lamotrigine) (Epilepsy), 2026 Limb defects 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 2.17 [0.83;5.66] -/-   -/- - -
ref
S17498
R73514		 Wiggs (Epilepsy) (Lamotrigine), 2024 Musculoskeletal system malformations early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 1.05 [0.72;1.52] -/1,412   -/9,364 - 1,412
ref
S8924
R48252		 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Skeletal malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.36 [0.06;28.82] C 0/50   2/340 2 50
ref
S8969
R30375		 Ban (Lamotrigine) (Mixed indications), 2015 Limb anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.50 [0.37;6.02] C 2/273   1,263/257,153 1,265 273
ref
S10292
R37691		 Vajda (Lamotrigine), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.15 [0.01;3.81] C 0/315   1/147 1 315
ref
S8909
R35289		 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 24.04 [0.96;601.51] C
excluded (control group) 		1/37   0/285 1 37
ref
S8910
R35293		 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No Matched 3.42 [0.14;86.71] C 1/37   0/41 1 37
ref
Total 6 studies 1.16 [0.83;1.62] 1,269 2,087
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 Seo (Lamotrigine) (Epilepsy), 2026Seo, 2026 1 2.17[0.83; 5.66]--12%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wiggs (Epilepsy) (Lamotrigine), 2024Wiggs, 2024 2 1.05[0.72; 1.52]-1,41279%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Thomas (Lamotrigine) (Controls unexposed, sick), 2021Thomas, 2021 3 1.36[0.06; 28.82]2501%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Ban (Lamotrigine) (Mixed indications), 2015Ban, 2015 4 1.50[0.37; 6.02]1,2652736%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Lamotrigine), 2013Vajda, 2013 5 0.15[0.01; 3.81]13151%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mawer (Lamotrigine) (Controls unexposed, sick), 2010Mawer, 2010 6 3.42[0.14; 86.71]1371%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 1.16[0.83; 1.62]1,2692,0870.010.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Epilepsy; 2: Epilepsy) (Lamotrigine; 3: Lamotrigine) (Controls unexposed, sick; 4: Lamotrigine) (Mixed indications; 5: Lamotrigine; 6: Lamotrigine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.16[0.83; 1.62]1,2692,0870%NASeo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.50[0.37; 6.02]1,265273 -NABan (Lamotrigine) (Mixed indications), 2015 1 unexposed, sickunexposed, sick 1.15[0.81; 1.61]41,8140%NASeo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 5 Tags Adjustment   - No  - No 1.24[0.41; 3.76]1,2696750%NAThomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 4   - Yes  - Yes 1.31[0.68; 2.53]-1,41248%NASeo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 2 MatchedMatched 3.42[0.14; 86.71]137 -NAMawer (Lamotrigine) (Controls unexposed, sick), 2010 1 All studiesAll studies 1.16[0.83; 1.62]1,2692,0870%NASeo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 60.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.94.01.9790.000Seo (Lamotrigine) (Epilepsy), 2026Wiggs (Epilepsy) (Lamotrigine), 2024Thomas (Lamotrigine) (Controls unexposed, sick), 2021Ban (Lamotrigine) (Mixed indications), 2015Vajda (Lamotrigine), 2013Mawer (Lamotrigine) (Controls unexposed, sick), 2010

Asymetry test p-value = 0.7274 (by Egger's regression)

slope=0.0843 (0.2438); intercept=0.2196 (0.5873); t=0.3739; p=0.7274

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8909

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 4.04[0.30; 54.91]1,26631058%NABan (Lamotrigine) (Mixed indications), 2015 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 2 unexposed, sick controlsunexposed, sick controls 1.15[0.81; 1.61]41,8140%NASeo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Weston (Skeletal / Limb Malformations)Weston (Skeletal / Limb Malformations) 0.72[0.12; 4.12]40-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Weston (Skeletal / Limb Malformations)Weston (Skeletal / Limb Malformations) Out of scale23.12[0.96; 558.25]NA-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT1 Bromley (Lamotrigine) (All indications) (Skel ...Bromley (Lamotrigine) (All indications) (Skeletal / Limb Malformations (Cohort studies)) Out of scale11.29[2.37; 53.91]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT5 Bromley (Lamotrigine) (All indications) (Skel ...Bromley (Lamotrigine) (All indications) (Skeletal / Limb Malformations (Cohort studies)) 0.75[0.20; 2.89]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 1.16[0.83; 1.62]0%2,087----Seo (Lamotrigine) (Epilepsy), 2026 Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 60.510.01.0