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

Psychomotor developmental 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.
S15218
R62401		 Bromley (Lamotrigine) (Epilepsy), 2023 Motor 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 1.17 [0.32;4.22] C 7/73   4/48 11 73
ref
S16614
R69686		 Thomas (Lamotrigine) (Epilepsy), 2022 The motor development quotient (MODQ) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 0.39 [0.18;0.85] -/26   -/110 - 26
ref
S8941
R30227		 Cohen-Israel (Lamotrigine), 2018 Motor delay (a majority between 6-12 years old) 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.20 [0.01;4.13] C 0/83   2/83 2 83
ref
S9947
R35773		 Videman (Lamotrigine), 2016 Griffiths Mental Developmental Scale - Locomotor (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 4.30 [1.10;16.79] -/8   -/59 - 8
ref
S8933
R30195		 Bromley (Lamotrigine) (Controls unexposed, disease free), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 22.47 [0.89;564.98] C
excluded (control group) 		1/30   0/214 1 30
ref
S8936
R30211		 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.68 [0.10;68.88] C 1/30   0/26 1 30
ref
S8952
R30285		 Rihtman (Lamotrigine), 2013 Miller Function and Participation Scales (MFUN) - Fine Motor (Preschool children: mean age 4-5y) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 2.79 [1.31;5.92] -/42   -/52 - 42
ref
Total 6 studies 1.30 [0.47;3.59] 14 262
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 Bromley (Lamotrigine) (Epilepsy), 2023Bromley, 2023 1 1.17[0.32; 4.22]117319%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Thomas (Lamotrigine) (Epilepsy), 2022Thomas, 2022 2 0.39[0.18; 0.85]-2624%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Cohen-Israel (Lamotrigine), 2018Cohen-Israel, 2018 3 0.20[0.01; 4.13]2838%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Videman (Lamotrigine), 2016Videman, 2016 4 4.30[1.10; 16.79]-818%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Bromley (Lamotrigine) (Controls unexposed, sick), 2013Bromley, 2013 5 2.68[0.10; 68.88]1307%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 6 2.79[1.31; 5.92]-4224%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 72% 1.30[0.47; 3.59]142620.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.30[0.47; 3.59]1426272%NABromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Cohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.47[0.88; 6.93]213339%NACohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Rihtman (Lamotrigine), 2013 3 unexposed, sickunexposed, sick 0.66[0.26; 1.70]1212933%NABromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 3 Tags Adjustment   - No  - No 1.30[0.47; 3.59]1426272%NABromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Cohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 6 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.59[0.35; 7.18]-7688%NAThomas (Lamotrigine) (Epilepsy), 2022 Videman (Lamotrigine), 2016 Rihtman (Lamotrigine), 2013 3 MatchedMatched 0.20[0.01; 4.13]283 -NACohen-Israel (Lamotrigine), 2018 1 All studiesAll studies 1.30[0.47; 3.59]1426272%NABromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Cohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 60.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.94.21.9870.000Bromley (Lamotrigine) (Epilepsy), 2023Thomas (Lamotrigine) (Epilepsy), 2022Cohen-Israel (Lamotrigine), 2018Videman (Lamotrigine), 2016Bromley (Lamotrigine) (Controls unexposed, sick), 2013Rihtman (Lamotrigine), 2013

Asymetry test p-value = 0.9569 (by Egger's regression)

slope=0.1623 (1.0844); intercept=0.1090 (1.8937); t=0.0575; p=0.9569

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8933

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.96[1.04; 8.44]316339%NACohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Bromley (Lamotrigine) (Controls unexposed, disease free), 2013 Rihtman (Lamotrigine), 2013 4 unexposed, sick controlsunexposed, sick controls 0.66[0.26; 1.70]1212933%NABromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Psychomotor developmental delay)Veroniki b (NMA) (Psychomotor developmental delay) 1.86[0.72; 4.76]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Peron (Epilepsy) (Psychomotor developmental d ...Peron (Epilepsy) (Psychomotor developmental disorders or delay) 2.68[1.29; 5.56]9%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 1.30[0.47; 3.59]72%262----Bromley (Lamotrigine) (Epilepsy), 2023 Thomas (Lamotrigine) (Epilepsy), 2022 Cohen-Israel (Lamotrigine), 2018 Videman (Lamotrigine), 2016 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 60.510.01.0