Lamotrigine (All indications) 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.
S17412
R73049		 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes Partial overlapping 0.86 [0.75;0.98] 243/5,035   147,608/2,651,210 147,851 5,035
ref
S17413
R73055		 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sibling) (Mixed indications), 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 sibling excluded Adjustment: Yes Partial overlapping 0.76 [0.56;1.03]
excluded (control group) 		-/-   -/- - -
ref
S17266
R72364		 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes 1.64 [0.93;2.89] 14/939   4,794/514,066 4,808 939
ref
S17274
R72365		 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, sibling) (Mixed indications), 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) sibling excluded Adjustment: Yes 5.97 [1.69;21.11]
excluded (control group) 		-/-   -/- - -
ref
S17470
R73447		 Dreier (Lamotrigine) (Epilepsy), 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
S8951
R39716		 Richards (Lamotrigine) (Indications NOS), 2019 The Strengths and Difficulties Questionnaire - parent-completed (SDQP) Hyperactivity ≥7 (at 4 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 2.15 [1.21;3.81] 13/149   11,841/286,966 11,854 149
ref
S8933
R39738		 Bromley (Lamotrigine) (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
S8936
R39741		 Bromley (Lamotrigine) (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
S8952
R39718		 Rihtman (Lamotrigine), 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
S8953
R39722		 Veiby (Lamotrigine) (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
S8954
R39723		 Veiby (Lamotrigine) (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 1.14 [0.86;1.53] 165,143 11,524
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 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_SE, 2024 1 0.86[0.75; 0.98]147,8515,03530%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK, 2024 2 1.64[0.93; 2.89]4,80893914%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Dreier (Lamotrigine) (Epilepsy), 2023Dreier, 2023 3 0.83[0.66; 1.04]6235,28827%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Richards (Lamotrigine) (Indications NOS), 2019Richards, 2019 4 2.15[1.21; 3.81]11,85414914%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Lamotrigine) (Controls unexposed, sick), 2013Bromley, 2013 5 0.86[0.02; 45.15]0301%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 6 1.21[0.57; 2.56]-3910%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013Veiby, 2013 7 2.74[0.59; 12.75]7443%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 64% 1.14[0.86; 1.53]165,14311,5240.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Controls unexposed, general pop) (Mixed indications; 2: Lamotrigine) (Controls unexposed, general pop) (Mixed indications; 3: Lamotrigine) (Epilepsy; 4: Lamotrigine) (Indications NOS; 5: Lamotrigine) (Controls unexposed, sick; 6: Lamotrigine; 7: Lamotrigine) (Controls unexposed, sick) ;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.86; 1.53]165,14311,52464%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Lamotrigine) (Epilepsy), 2023 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (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) 1.33[0.80; 2.20]164,5136,16278%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Richards (Lamotrigine) (Indications NOS), 2019 Rihtman (Lamotrigine), 2013 4 unexposed, sickunexposed, sick 0.95[0.55; 1.64]6305,36212%NADreier (Lamotrigine) (Epilepsy), 2023 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 3 Tags Adjustment   - No  - No 1.40[0.72; 2.72]71130%NABromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 3   - Yes  - Yes 1.11[0.80; 1.54]165,13611,41179%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Lamotrigine) (Epilepsy), 2023 Richards (Lamotrigine) (Indications NOS), 2019 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.21[0.57; 2.56]-39 -NARihtman (Lamotrigine), 2013 1 Partial overlappingPartial overlapping 0.86[0.75; 0.98]147,8515,035 -NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 1 All studiesAll studies 1.14[0.86; 1.53]165,14311,52464%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Lamotrigine) (Epilepsy), 2023 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 70.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.92.4220.000Madley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024Dreier (Lamotrigine) (Epilepsy), 2023Richards (Lamotrigine) (Indications NOS), 2019Bromley (Lamotrigine) (Controls unexposed, sick), 2013Rihtman (Lamotrigine), 2013Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013

Asymetry test p-value = 0.0713 (by Egger's regression)

slope=-0.2611 (0.1038); intercept=1.6057 (0.7034); t=2.2827; p=0.0713

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8933, 8953, 17413, 17274

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.37[0.87; 2.16]166,2596,23668%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, disease free), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013 6 unexposed, sick controlsunexposed, sick controls 0.95[0.55; 1.64]6305,36212%NADreier (Lamotrigine) (Epilepsy), 2023 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 3 siblingssiblings 1.94[0.26; 14.48]--90%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sibling) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, sibling) (Mixed indications), 2024 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Xu (All indications) (ADHD)Xu (All indications) (ADHD) 0.87[0.71; 1.06]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Veroniki b (NMA) (Attention deficit hyperacti ...Veroniki b (NMA) (Attention deficit hyperactivity disorder) 1.63[0.41; 6.06]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 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 1.14[0.86; 1.53]64%11,524----Madley-Dowd_SE (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Lamotrigine) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Lamotrigine) (Epilepsy), 2023 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 70.510.01.0