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

ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk

id	Study   Auto Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Madley-Dowd_SE (Levetiracetam) (Controls exposed to LTG) (Mixed indications), 2024Madley-Dowd_SE (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_SE (Levetiracetam) (Controls unexposed, sibling) (Mixed indications), 2024Madley-Dowd_UK (Levetiracetam) (Controls exposed to LTG) (Mixed indications), 2024Madley-Dowd_UK (Levetiracetam) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK (Levetiracetam) (Controls unexposed, sibling) (Mixed indications), 2024Dreier (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Huber-Mollema (Levetiracetam), 2019Bromley (Levetiracetam), 2016	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S19378 R82481	Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026	Attention deficit hyperactivity disorder (ADHD) - ICD-10 codes: F90.x - Mean follow up (full cohort): 3.4 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	0.56 [0.41;0.76] C excluded (control group)	69/3,929   102/3,273	171	3,929		ref
S19369 R82488	Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026	Attention deficit hyperactivity disorder (ADHD) - ICD-10 codes: F90.x - Mean follow up (full cohort): 3.4 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes	0.89 [0.68;1.17]	69/3,929   366/8,887	435	3,929		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	6 studies	1.04 [0.79;1.37]		148,604	5,868
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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 15238, 17414, 17416, 17282, 17275, 19378