Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) updated on 07-01-2025

Respiratory system anomalies

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.
S18317
R77149
Chan (Controls unexposed, sick), 2024 Respiratory system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 2.17 [0.13;36.58] C 0/66   15/4,413 15 66
ref
S18315
R77125
Chan - SNRI (Controls exposed to TCA), 2024 Respiratory system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.84 [0.04;17.58] C
excluded (control group)
0/77   2/322 2 77
ref
S18316
R77137
Chan - SNRI (Controls unexposed, general pop), 2024 Respiratory system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: No Monotherapy: SNRI only 2.50 [0.15;40.36] C
excluded (control group)
0/77   1,205/462,377 1,205 77
ref
S15171
R62283
Benevent - SNRI, 2023 Respiratory system anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SNRI only 6.24 [0.38;101.91] C 0/314   37/146,855 37 314
ref
S11684
R42950
Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021 Respiratory malformations 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.92 [0.26;3.24]
excluded (control group)
-/1,438   13/5,751 - 1,438
ref
S11685
R42966
Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Respiratory malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.50 [0.25;8.98] -/1,434   -/1,435 - 1,434
ref
S11745
R43132
Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Respiratory malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.87 [0.39;1.94]
excluded (control group)
-/2,532   -/- - 2,532
ref
S11746
R43146
Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Respiratory malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.89 [0.29;2.75] -/2,532   -/2,456 - 2,532
ref
S11696
R43027
Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Respiratory system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 2.17 [1.07;4.38] -/738   -/14,847 - 738
ref
Total 5 studies 1.77 [1.03;3.05] 52 5,084
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 (Controls unexposed, sick), 2024Chan, 2024 1 2.17[0.13; 36.58]15664%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Benevent - SNRI, 2023Benevent - SNRI, 2023 6.24[0.38; 101.91]373144%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Ankarfeldt a - Duloxetine, 2021 2 1.50[0.25; 8.98]-1,4349%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: low Huybrechts - Duloxetine (Controls unexposed, sick), 2020Huybrechts - Duloxetine, 2020 3 0.89[0.29; 2.75]-2,53223%ROB confusion: moderateROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: low Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017Bérard b - SNRI=Venlafaxine, 2017 4 2.17[1.07; 4.38]-73860%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.77[1.03; 3.05]525,0840.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.77[1.03; 3.05]525,0840%NAChan (Controls unexposed, sick), 2024 Benevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 6.24[0.38; 101.91]37314 -NABenevent - SNRI, 2023 1 unexposed, sickunexposed, sick 1.68[0.97; 2.94]154,7700%NAChan (Controls unexposed, sick), 2024 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 4 Tags Adjustment   - No  - No 3.70[0.51; 26.98]523800%NAChan (Controls unexposed, sick), 2024 Benevent - SNRI, 2023 2   - Yes  - Yes 1.67[0.95; 2.94]-4,7040%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 3 Monotherapy   - no or not specified  - no or not specified 1.03[0.40; 2.67]-3,9660%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 2   - SNRI only  - SNRI only 2.31[1.17; 4.58]371,0520%NABenevent - SNRI, 2023 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 2   - SSRI only  - SSRI only 2.17[0.13; 36.58]1566 -NAChan (Controls unexposed, sick), 2024 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.67[0.95; 2.94]-4,7040%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 3   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 2.17[0.13; 36.58]1566 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.77[1.03; 3.05]525,0840%NAChan (Controls unexposed, sick), 2024 Benevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 50.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.44.01.7310.000Chan (Controls unexposed, sick), 2024Benevent - SNRI, 2023Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Huybrechts - Duloxetine (Controls unexposed, sick), 2020Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017

Asymetry test p-value = 0.8503 (by Egger's regression)

slope=0.4777 (0.5238); intercept=0.1732 (0.8428); t=0.2056; p=0.8503

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 11745, 11684, 18315, 18316

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.55; 1.96]1,2464,3610%NAChan - SNRI (Controls unexposed, general pop), 2024 Benevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 4 unexposed, sick controlsunexposed, sick controls 1.68[0.97; 2.94]154,7700%NAChan (Controls unexposed, sick), 2024 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.84[0.04; 17.58]277 -NAChan - SNRI (Controls exposed to TCA), 2024 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SNRIs (Congenital malformations of th ...Huang - SNRIs (Congenital malformations of the respiratory system) 1.51[0.49; 4.70]NA-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT1 Lou - SNRIs (Respiratory malformations)Lou - SNRIs (Respiratory malformations) 0.80[0.37; 1.74]0%-Eexposed to other treatment, sickT11st trimesterstudies TTT2 Lou - SNRIs (Respiratory malformations)Lou - SNRIs (Respiratory malformations) 1.67[0.95; 2.94]0%-U,Sunexposed, sickT11st trimesterstudies TTT3 Lou - SNRIs (Respiratory malformations)Lou - SNRIs (Respiratory malformations) 0.88[0.45; 1.74]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT2 metaPregmetaPreg 1.77[1.03; 3.05]0%5,084----Chan (Controls unexposed, sick), 2024 Benevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 50.510.01.0