Levetiracetam (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.
S17414
R73067		 Madley-Dowd_SE (Levetiracetam) (Controls exposed to LTG) (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 exposed to other treatment, sick excluded Adjustment: Yes Partial overlapping 1.18 [0.69;2.02]
excluded (control group) 		14/613   243/5,035 257 613
ref
S17415
R73071		 Madley-Dowd_SE (Levetiracetam) (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 1.02 [0.60;1.72] 14/613   147,608/2,651,210 147,622 613
ref
S17416
R73075		 Madley-Dowd_SE (Levetiracetam) (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 1.06 [0.30;3.77]
excluded (control group) 		-/-   -/- - -
ref
S17282
R72366		 Madley-Dowd_UK (Levetiracetam) (Controls exposed to LTG) (Mixed indications), 2024 Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median 4.19 (2.56-6.79) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 0.90 [0.16;5.10]
excluded (control group) 		-/193   14/939 - 193
ref
S17267
R72367		 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median 4.19 (2.56-6.79) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.48 [0.28;7.83] -/193   4,794/514,066 - 193
ref
S17275
R72368		 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, sibling) (Mixed indications), 2024 Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median 4.19 (2.56-6.79) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) sibling excluded Adjustment: Yes 4.06 [0.52;31.68]
excluded (control group) 		-/-   -/- - -
ref
S15238
R63062		 Dreier (Levetiracetam) (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 0.73 [0.42;1.29] C
excluded (control group) 		14/1,061   95/5,288 109 1,061
ref
S15230
R63063		 Dreier (Levetiracetam) (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 1.78 [1.03;3.07] 14/1,061   528/22,203 542 1,061
ref
S9022
R46401		 Huber-Mollema (Levetiracetam), 2019 Diagnosis of ADHD throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 0.25 [0.01;4.74] C 0/30   5/88 5 30
ref
S9018
R46402		 Bromley (Levetiracetam), 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) 0.86 [0.41;1.78] -/42   -/55 - 42
ref
Total 5 studies 1.19 [0.84;1.70] 148,169 1,939
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 (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_SE, 2024 1 1.02[0.60; 1.72]147,62261338%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK, 2024 2 1.48[0.28; 7.83]-1934%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 3 1.78[1.03; 3.07]5421,06135%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Huber-Mollema (Levetiracetam), 2019Huber-Mollema, 2019 4 0.25[0.01; 4.74]5301%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Levetiracetam), 2016Bromley, 2016 5 0.86[0.41; 1.78]-4221%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 7% 1.19[0.84; 1.70]148,1691,9390.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam) (Controls unexposed, general pop) (Mixed indications; 2: Levetiracetam) (Controls unexposed, general pop) (Mixed indications; 3: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 4: Levetiracetam; 5: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.19[0.84; 1.70]148,1691,9397%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Huber-Mollema (Levetiracetam), 2019 Bromley (Levetiracetam), 2016 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.06[0.64; 1.74]147,6228060%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 2 unexposed, sickunexposed, sick 1.29[0.64; 2.62]5421,10359%NADreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Levetiracetam), 2016 2 exposed to other treatment, sickexposed to other treatment, sick 0.25[0.01; 4.74]530 -NAHuber-Mollema (Levetiracetam), 2019 1 Tags Adjustment   - No  - No 0.80[0.39; 1.63]5720%NAHuber-Mollema (Levetiracetam), 2019 Bromley (Levetiracetam), 2016 2   - Yes  - Yes 1.34[0.92; 1.97]148,1641,8674%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 0.86[0.41; 1.79]-42 -NABromley (Levetiracetam), 2016 1 Partial overlappingPartial overlapping 1.02[0.60; 1.73]147,622613 -NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 1 All studiesAll studies 1.19[0.84; 1.70]148,1691,9397%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Huber-Mollema (Levetiracetam), 2019 Bromley (Levetiracetam), 2016 50.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.71.7910.000Madley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Huber-Mollema (Levetiracetam), 2019Bromley (Levetiracetam), 2016

Asymetry test p-value = 0.4911 (by Egger's regression)

slope=0.4557 (0.3928); intercept=-0.8211 (1.0496); t=0.7823; p=0.4911

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 15238, 17414, 17416, 17282, 17275

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.06[0.64; 1.74]152,4078060%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024 2 unexposed, sick controlsunexposed, sick controls 1.29[0.64; 2.62]5421,10359%NADreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Levetiracetam), 2016 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.92[0.63; 1.34]3761,8970%NAMadley-Dowd_SE (Levetiracetam) (Controls exposed to LTG) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls exposed to LTG) (Mixed indications), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Huber-Mollema (Levetiracetam), 2019 4 siblingssiblings 1.61[0.48; 5.44]--16%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sibling) (Mixed indications), 2024 Madley-Dowd_UK (Levetiracetam) (Controls unexposed, sibling) (Mixed indications), 2024 20.510.01.0