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

Cognitive developmental disorders/delay (3-6 years old)

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.
S12727
R53704		 Bjørk (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - Median follow up lamotrigine 5.1 (2.4-8.5) years old during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes 1.34 [0.92;1.95]
excluded (control group) 		27/7,950   16,384/4,463,879 16,411 7,950
ref
S12728
R53705		 Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - Median follow up lamotrigine 5.1 (2.4-8.5) years old during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 0.53 [0.35;0.80] C 27/7,950   139/21,634 166 7,950
ref
S8978
R40018		 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Diagnosis Mental retardation (F70–F79) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 2.40 [1.40;4.00] 15/2,813   3,385/1,707,707 3,400 2,813
ref
S8950
R40020		 Kasradze (Lamotrigine), 2017 Full scale IQ (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 30.10 [3.28;276.62] -/3   -/50 - 3
ref
S8952
R40021		 Rihtman (Lamotrigine), 2013 Stanford Binet Intelligence Scales, Fifth Edition (SB5) - GIQ (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 1.65 [0.78;3.49] -/41   -/52 - 41
ref
S8942
R40022		 Cummings (Lamotrigine), 2011 Mild or significant delay (score ≥1, <2 SD or ≥2 SD below the mean) (Bayley Scales of Infant Development or the Griffiths Scale) (mean age in years: m1=2.7 and m0=4.3) throughout pregnancy retrospective cohort (registry) unexposed, disease free Adjustment: Yes 1.10 [0.10;13.70] 1/35   2/44 3 35
ref
Total 5 studies 1.81 [0.66;4.98] 3,569 10,842
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 Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022Bjørk, 2022 1 0.53[0.35; 0.80]1667,95027%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Coste, 2020 2 2.40[1.40; 4.00]3,4002,81326%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Kasradze (Lamotrigine), 2017Kasradze, 2017 3 30.10[3.28; 276.62]-312%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 4 1.65[0.78; 3.49]-4124%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cummings (Lamotrigine), 2011Cummings, 2011 5 1.10[0.10; 13.70]33511%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Total (5 studies) I2 = 87% 1.81[0.66; 4.98]3,56910,8420.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.81[0.66; 4.98]3,56910,84287%NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 Cummings (Lamotrigine), 2011 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.53[1.15; 5.56]3,4032,89252%NACoste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 Cummings (Lamotrigine), 2011 4 unexposed, sickunexposed, sick 0.53[0.35; 0.80]1667,950 -NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 1 Tags Adjustment   - No  - No 1.93[0.45; 8.41]1667,99489%NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 3   - Yes  - Yes 2.32[1.39; 3.88]3,4032,8480%NACoste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Cummings (Lamotrigine), 2011 2 Controls   - epilepsy indication  - epilepsy indication 0.53[0.35; 0.80]1667,950 -NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 5.80[0.35; 97.25]-4483%NAKasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 2 MatchedMatched 30.10[3.28; 276.42]-3 -NAKasradze (Lamotrigine), 2017 1 All studiesAll studies 1.81[0.66; 4.98]3,56910,84287%NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 Cummings (Lamotrigine), 2011 50.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.14.11.5060.000Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Kasradze (Lamotrigine), 2017Rihtman (Lamotrigine), 2013Cummings (Lamotrigine), 2011

Asymetry test p-value = 0.3400 (by Egger's regression)

slope=-0.6532 (0.7663); intercept=2.5941 (2.2919); t=1.1319; p=0.3400

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 12727

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.98[1.13; 3.47]19,81410,84259%NABjørk (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2022 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 Cummings (Lamotrigine), 2011 5 unexposed, sick controlsunexposed, sick controls 0.53[0.35; 0.80]1667,950 -NABjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Peron (Epilepsy) (Cognitive developmental del ...Peron (Epilepsy) (Cognitive developmental delay (3-6 years old)) 3.39[0.56; 20.57]68%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.81[0.66; 4.98]87%10,842----Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Kasradze (Lamotrigine), 2017 Rihtman (Lamotrigine), 2013 Cummings (Lamotrigine), 2011 50.510.01.0