Benzodiazepines (Psy and mixed indications) updated on 02-10-2025

ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk

id	Study   Auto Chan - BZDs, 2023Chen - BZDs (Controls unexposed, NOS), 2022Chen - BZDs (Controls unexposed, sibling), 2022Chen - BZDs (Controls unexposed, sick), 2022Christensen - Clonazepam (Indications NOS), 2019Lupattelli - BZDs, 2019Figueroa - BZDs, 2010Viggedal - BZDs, 1993	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 trimester	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.
S15397 R64483	Chan - BZDs, 2023	Attention-deficit/hyperactivity disorder (ADHD) - ICD-9-CM: 314, or prescription for ADHD medication, namely methylphenidate or atomoxetine - Median follow-up time of 10.91 years	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.03 [0.77;1.37]	-/-   -/-	-	-		ref
S15460 R64484	Chen - BZDs (Controls unexposed, NOS), 2022	Attention-Deficit/Hyperactivity Disorders ADHD (ICD-9 code 314; ICD-10 code F90) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes BZD Coexposure: Not specified	1.06 [1.02;1.10] excluded (control group)	3,430/70,451   55,556/1,440,435	58,986	70,451		ref
S15638 R64543	Chen - BZDs (Controls unexposed, sibling), 2022	Attention-Deficit/Hyperactivity Disorders ADHD (ICD-9 code 314; ICD-10 code F90) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	sibling excluded	Adjustment: Yes BZD Coexposure: Not specified	0.91 [0.83;1.00] excluded (control group)	-/26,652   -/29,233	-	26,652		ref
S17008 R71238	Chen - BZDs (Controls unexposed, sick), 2022	Attention-Deficit/Hyperactivity Disorders ADHD (ICD-9 code 314; ICD-10 code F90) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes BZD Coexposure: Not specified	1.02 [0.93;1.12]	-/8,492   -/30,832	-	8,492		ref
S15625 R64500	Christensen - Clonazepam (Indications NOS), 2019	ADHD Diagnoses with follow up from birth	during pregnancy (anytime or not specified)	population based cohort propective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among antiseizure medications)	1.43 [0.95;2.16]	25/314   27,832/883,311	27,857	314		ref
S15471 R64485	Lupattelli - BZDs, 2019	Attention-deficit/ hyperactivity disorder (ADHD) symptoms - Conners’ Parent Rating Scale–Revised (12 items) - Median age of 5.1 years (interquartile range, 5.0-5.3 years)	late pregnancy	prospective cohort	unexposed, sick	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...)	1.34 [1.02;1.77]	-/23   -/-	-	23		ref
S18371 R77446	Figueroa - BZDs, 2010	Attention-deficit/hyperactivity disorder (ADHD - primary or secondary diagnosis of ADHD and prescription claims for stimulants) - At 4-5 years old	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes BZD Coexposure: Not specified	1.82 [0.86;3.85]	8/311   88/3,532	96	311		ref
S15481 R64486	Viggedal - BZDs, 1993	Short attention span - A neuropsychological 3-point scale - At 18 months	throughout pregnancy	prospective cohort	unexposed, disease free	Adjustment: No BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...)	5.23 [0.87;31.32] C	5/16   2/25	7	16		ref
					Total	6 studies	1.20 [0.99;1.46]		27,960	9,156
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 15460, 15638