Clonazepam (Psy and Mixed indications) updated on 02-10-2025

Major congenital malformations

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.
S17867
R75482		 The NAAED (Indications NOS), 2023 Major congenital malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No BZD Coexposure: No (among antiseizure medications) 2.25 [0.64;7.88] C 3/120   15/1,330 18 120
ref
S15391
R63454		 Noh (Mixed indications), 2022 Overall major congenital malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.02 [0.82;1.25] 93/1,454   156,896/3,053,381 156,989 1,454
ref
S15646
R64569		 Veiby (Mixed indications), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free Adjustment: Yes BZD Coexposure: No (among antiseizure medications) 0.65 [0.16;2.62] 2/113   22,371/771,412 22,373 113
ref
S15586
R64140		 Källén (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: No (among antiseizure medications) 1.31 [0.42;3.05] 5/106   49,499/1,575,847 49,504 106
ref
S17865
R75457		 Eros (Indications NOS), 2002 Major congenital anomalies during pregnancy (anytime or not specified) excluded case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 1.70 [0.50;6.20]
excluded (exposition period) 		4/8   22,861/61,008 22,865 8
ref
Total 4 studies 1.04 [0.85;1.27] 228,884 1,793
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 The NAAED (Indications NOS), 2023The NAAED, 2023 1 2.25[0.64; 7.88]181203%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: low Noh (Mixed indications), 2022Noh, 2022 2 1.02[0.82; 1.25]156,9891,45491%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Veiby (Mixed indications), 2014Veiby, 2014 3 0.65[0.16; 2.62]22,3731132%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Indications NOS), 2013Källén, 2013 4 1.31[0.42; 3.05]49,5041064%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (4 studies) I2 = 0% 1.04[0.85; 1.27]228,8841,7930.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Indications NOS; 2: Mixed indications; 3: Mixed indications; 4: Indications NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.04[0.85; 1.27]228,8841,7930%NAThe NAAED (Indications NOS), 2023 Noh (Mixed indications), 2022 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[0.66; 2.57]71,8953390%NAThe NAAED (Indications NOS), 2023 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 3 unexposed, sickunexposed, sick 1.02[0.83; 1.26]156,9891,454 -NANoh (Mixed indications), 2022 1 Tags Adjustment   - No  - No 2.25[0.64; 7.88]18120 -NAThe NAAED (Indications NOS), 2023 1   - Yes  - Yes 1.02[0.83; 1.25]228,8661,6730%NANoh (Mixed indications), 2022 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 3 BZD Coexposure   - No (among antiseizure medications)  - No (among antiseizure medications) 1.30[0.66; 2.57]71,8953390%NAThe NAAED (Indications NOS), 2023 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 3   - Not specified  - Not specified 1.02[0.83; 1.26]156,9891,454 -NANoh (Mixed indications), 2022 1 All studiesAll studies 1.04[0.85; 1.27]228,8841,7930%NAThe NAAED (Indications NOS), 2023 Noh (Mixed indications), 2022 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.70.8560.000The NAAED (Indications NOS), 2023Noh (Mixed indications), 2022Veiby (Mixed indications), 2014Källén (Indications NOS), 2013

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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.30[0.66; 2.57]71,8953390%NAThe NAAED (Indications NOS), 2023 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 3 unexposed, sick controlsunexposed, sick controls 1.02[0.83; 1.26]156,9891,454 -NANoh (Mixed indications), 2022 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (Cohort studies)) 2.76[0.55; 13.94]NA-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT2 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (Cohort studies)) 1.08[0.21; 5.42]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (Cohort studies)) 1.09[0.34; 3.49]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (database studies)) 0.70[0.18; 2.77]NA-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT1 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (database studies)) 0.69[0.17; 2.79]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT1 Bromley (Clonazepam) (All indications) (All M ...Bromley (Clonazepam) (All indications) (All Major Malformations (Database studies)) 0.65[0.22; 1.89]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Veroniki a (NMA) (Clonazepam) (All indication ...Veroniki a (NMA) (Clonazepam) (All indications) (Overall major congenital malformations) 1.13[0.59; 2.02]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.04[0.85; 1.27]0%1,793----The NAAED (Indications NOS), 2023 Noh (Mixed indications), 2022 Veiby (Mixed indications), 2014 Källén (Indications NOS), 2013 40.510.01.0