Lamotrigine (All indications)

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.
S15229
R63061
Dreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 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
S8956
R39729
Wiggs (Lamotrigine), 2020 Attention-deficit/hyperactivity disorder (after 2 years of age) at least 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 1.00 [0.59;1.69] -/-   -/11,298 - -
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 6 studies 1.21 [0.81;1.81] 12,484 5,550
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 Dreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 1 0.83[0.66; 1.04]6235,28833%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Wiggs (Lamotrigine), 2020Wiggs, 2020 2 1.00[0.59; 1.69]--23%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Richards (Lamotrigine) (Indications NOS), 2019Richards, 2019 3 2.15[1.21; 3.81]11,85414921%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Lamotrigine) (Controls unexposed, sick), 2013Bromley, 2013 4 0.86[0.02; 45.15]0301%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 5 1.21[0.57; 2.56]-3916%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013Veiby, 2013 6 2.74[0.59; 12.75]7446%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 56% 1.21[0.81; 1.81]12,4845,5500.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.21[0.81; 1.81]12,4845,55056%NADreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Lamotrigine), 2020 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.70[0.98; 2.96]11,85418830%NARichards (Lamotrigine) (Indications NOS), 2019 Rihtman (Lamotrigine), 2013 2 unexposed, sickunexposed, sick 0.87[0.71; 1.07]6305,3620%NADreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Lamotrigine), 2020 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 4 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 1.16[0.68; 1.99]12,4775,43778%NADreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Lamotrigine), 2020 Richards (Lamotrigine) (Indications NOS), 2019 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.21[0.57; 2.56]-39 -NARihtman (Lamotrigine), 2013 1 All studiesAll studies 1.21[0.81; 1.81]12,4845,55056%NADreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Lamotrigine), 2020 Richards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.92.4220.000Dreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023Wiggs (Lamotrigine), 2020Richards (Lamotrigine) (Indications NOS), 2019Bromley (Lamotrigine) (Controls unexposed, sick), 2013Rihtman (Lamotrigine), 2013Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013

Asymetry test p-value = 0.1965 (by Egger's regression)

slope=-0.2723 (0.2078); intercept=1.3679 (0.8837); t=1.5480; p=0.1965

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8933, 8953

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.74[1.14; 2.66]13,6002620%NARichards (Lamotrigine) (Indications NOS), 2019 Bromley (Lamotrigine) (Controls unexposed, disease free), 2013 Rihtman (Lamotrigine), 2013 Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013 4 unexposed, sick controlsunexposed, sick controls 0.87[0.71; 1.07]6305,3620%NADreier (Lamotrigine) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Lamotrigine), 2020 Bromley (Lamotrigine) (Controls unexposed, sick), 2013 Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013 40.510.01.0