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

ADHD (Attention deficit hyperactivity disorder): Diagnosis

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.
S15397
R63469
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
R63566
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
R64537
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
R71232
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
R64498
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   28,752/899,941 28,777 314
ref
S18371
R77442
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
Total 4 studies 1.11 [0.93;1.32] 28,873 9,117
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 Chan - BZDs, 2023Chan - BZDs, 2023 1.03[0.77; 1.37]--24%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Chen - BZDs (Controls unexposed, sick), 2022Chen - BZDs, 2022 1 1.02[0.93; 1.12]-8,49257%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Christensen - Clonazepam (Indications NOS), 2019Christensen - Clonazepam, 2019 2 1.43[0.95; 2.16]28,77731414%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Figueroa - BZDs, 2010Figueroa - BZDs, 2010 1.82[0.86; 3.85]963115%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 35% 1.11[0.93; 1.32]28,8739,1170.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Indications NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.11[0.93; 1.32]28,8739,11735%NAChan - BZDs, 2023 Chen - BZDs (Controls unexposed, sick), 2022 Christensen - Clonazepam (Indications NOS), 2019 Figueroa - BZDs, 2010 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.17[0.86; 1.61]28,77731439%NAChan - BZDs, 2023 Christensen - Clonazepam (Indications NOS), 2019 2 unexposed, sickunexposed, sick 1.20[0.72; 2.01]968,80356%NAChen - BZDs (Controls unexposed, sick), 2022 Figueroa - BZDs, 2010 2 Tags Adjustment   - Yes  - Yes 1.11[0.93; 1.32]28,8739,11735%NAChan - BZDs, 2023 Chen - BZDs (Controls unexposed, sick), 2022 Christensen - Clonazepam (Indications NOS), 2019 Figueroa - BZDs, 2010 4 BZD Coexposure   - No (among antiseizure medications)  - No (among antiseizure medications) 1.43[0.95; 2.16]28,777314 -NAChristensen - Clonazepam (Indications NOS), 2019 1   - Not specified  - Not specified 1.20[0.72; 2.01]968,80356%NAChen - BZDs (Controls unexposed, sick), 2022 Figueroa - BZDs, 2010 2   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.03[0.77; 1.37]-- -NAChan - BZDs, 2023 1 All studiesAll studies 1.11[0.93; 1.32]28,8739,11735%NAChan - BZDs, 2023 Chen - BZDs (Controls unexposed, sick), 2022 Christensen - Clonazepam (Indications NOS), 2019 Figueroa - BZDs, 2010 40.55.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-0.91.00.4590.000Chan - BZDs, 2023Chen - BZDs (Controls unexposed, sick), 2022Christensen - Clonazepam (Indications NOS), 2019Figueroa - BZDs, 2010

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 15460, 15638

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.06[1.01; 1.13]87,76370,7653%NAChan - BZDs, 2023 Chen - BZDs (Controls unexposed, NOS), 2022 Christensen - Clonazepam (Indications NOS), 2019 3 unexposed, sick controlsunexposed, sick controls 1.20[0.72; 2.01]968,80356%NAChen - BZDs (Controls unexposed, sick), 2022 Figueroa - BZDs, 2010 2 siblingssiblings 0.91[0.83; 1.00]-26,652 -NAChen - BZDs (Controls unexposed, sibling), 2022 10.510.01.0