Topiramate (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.
S15240
R63066		 Dreier (Topiramate) (Epilepsy) (Controls exposed to LTG), 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 exposed to other treatment, sick excluded Adjustment: No 3.19 [1.85;5.50] C
excluded (control group) 		16/290   95/5,288 111 290
ref
S15233
R63067		 Dreier (Topiramate) (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 2.38 [1.40;4.06] 16/290   528/22,203 544 290
ref
S8589
R48828		 Richards (Topiramate) (Controls exposed to Lamotrigine, sick) (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 exposed to other treatment, sick excluded Adjustment: No 0.18 [0.01;3.16] C
excluded (control group) 		0/28   13/149 13 28
ref
S8590
R48829		 Richards (Topiramate) (Controls unexposed, NOS) (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: No 0.42 [0.03;6.93] C 0/28   11,841/286,966 11,841 28
ref
S8582
R48827		 Bromley (Topiramate), 2016 Maladaptive behavior: Attention (BASC) (5-9 years old) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.00 [0.43;2.31] -/27   -/55 - 27
ref
S8615
R48830		 Rihtman (Topiramate) (Mixed indications), 2012 Cognitive problems/inattention (Parent questionnaire) (Conners' rating scale - revised) (mean age around 4 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 4.37 [0.91;21.04] -/8   -/18 - 8
ref
Total 4 studies 1.78 [0.89;3.56] 12,385 353
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 (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 1 2.38[1.40; 4.06]54429046%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Richards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019Richards, 2019 2 0.42[0.03; 6.93]11,841286%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Topiramate), 2016Bromley, 2016 3 1.00[0.43; 2.31]-2733%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rihtman (Topiramate) (Mixed indications), 2012Rihtman, 2012 4 4.37[0.91; 21.04]-815%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 41% 1.78[0.89; 3.56]12,3853530.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Topiramate) (Epilepsy) (Controls unexposed, sick; 2: Topiramate) (Controls unexposed, NOS) (Indications NOS; 3: Topiramate; 4: Topiramate) (Mixed indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.78[0.89; 3.56]12,38535341%NADreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Richards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.83[0.20; 16.76]11,8413651%NARichards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019 Rihtman (Topiramate) (Mixed indications), 2012 2 unexposed, sickunexposed, sick 1.64[0.71; 3.81]54431766%NADreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 2 Tags Adjustment   - No  - No 1.41[0.46; 4.32]11,8416339%NARichards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 3   - Yes  - Yes 2.38[1.40; 4.05]544290 -NADreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.79[0.44; 7.35]-3562%NABromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 2 MatchedMatched 4.37[0.91; 21.01]-8 -NARihtman (Topiramate) (Mixed indications), 2012 1 All studiesAll studies 1.78[0.89; 3.56]12,38535341%NADreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Richards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.43.91.7120.000Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023Richards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019Bromley (Topiramate), 2016Rihtman (Topiramate) (Mixed indications), 2012

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8589, 15240

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.83[0.20; 16.76]11,8413651%NARichards (Topiramate) (Controls unexposed, NOS) (Indications NOS), 2019 Rihtman (Topiramate) (Mixed indications), 2012 2 unexposed, sick controlsunexposed, sick controls 1.64[0.71; 3.81]54431766%NADreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Topiramate), 2016 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.09[0.07; 16.48]12431873%NADreier (Topiramate) (Epilepsy) (Controls exposed to LTG), 2023 Richards (Topiramate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2019 20.510.01.0