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

Digestive 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.
S15171
R62285
Benevent - SNRI, 2023 Digestive system anomalites 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SNRI only 2.99 [0.42;21.39] C 1/314   157/146,855 158 314
ref
S11684
R42942
Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021 Digestive system malformation 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.25 [0.79;1.99]
excluded (control group)
24/1,438   77/5,751 101 1,438
ref
S11685
R42958
Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Digestive system malformation 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) 1.60 [0.84;3.05] 24/1,434   15/1,435 39 1,434
ref
S11745
R43134
Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Gastrointestinal malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.86 [0.48;1.55]
excluded (control group)
-/2,532   -/- - 2,532
ref
S11746
R43148
Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Gastrointestinal 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) 0.67 [0.31;1.45] -/2,532   -/2,456 - 2,532
ref
S11696
R43028
Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Digestive 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) 0.89 [0.44;1.83] -/738   -/14,847 - 738
ref
Total 4 studies 1.08 [0.66;1.78] 197 5,018
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 Benevent - SNRI, 2023Benevent - SNRI, 2023 2.99[0.42; 21.39]1583146%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Ankarfeldt a - Duloxetine, 2021 1 1.60[0.84; 3.05]391,43435%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: low Huybrechts - Duloxetine (Controls unexposed, sick), 2020Huybrechts - Duloxetine, 2020 2 0.67[0.31; 1.45]-2,53228%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 3 0.89[0.44; 1.83]-73831%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 29% 1.08[0.66; 1.78]1975,0180.210.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.08[0.66; 1.78]1975,01829%NABenevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.99[0.42; 21.39]158314 -NABenevent - SNRI, 2023 1 unexposed, sickunexposed, sick 1.02[0.61; 1.70]394,70436%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 3 Tags Adjustment   - No  - No 2.99[0.42; 21.39]158314 -NABenevent - SNRI, 2023 1   - Yes  - Yes 1.02[0.61; 1.70]394,70436%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 1.06[0.45; 2.49]393,96665%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 2   - SNRI only  - SNRI only 1.13[0.44; 2.93]1581,05222%NABenevent - SNRI, 2023 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 2 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.02[0.61; 1.70]394,70436%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 3 All studiesAll studies 1.08[0.66; 1.78]1975,01829%NABenevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.41.2060.000Benevent - SNRI, 2023Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Huybrechts - Duloxetine (Controls unexposed, sick), 2020Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017

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 11745, 11684

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.12[0.78; 1.60]2594,2840%NABenevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 3 unexposed, sick controlsunexposed, sick controls 1.02[0.61; 1.70]394,70436%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SNRIs (Abdominal birth defects)Huang - SNRIs (Abdominal birth defects) 2.91[1.98; 4.28]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Huang - SNRIs (Congenital anomalies of the di ...Huang - SNRIs (Congenital anomalies of the digestive system) 2.05[1.60; 2.64]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Lou - SNRIs (Digestive malformations)Lou - SNRIs (Digestive malformations) 1.18[0.79; 1.77]0%-Eexposed to other treatment, sickT11st trimesterstudies TTT2 Lou - SNRIs (Digestive malformations)Lou - SNRIs (Digestive malformations) 1.04[0.69; 1.56]0%-U,Sunexposed, sickT11st trimesterstudies TTT3 Lou - SNRIs (Digestive malformations)Lou - SNRIs (Digestive malformations) 1.08[0.75; 1.56]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT2 metaPregmetaPreg 1.08[0.66; 1.78]29%5,018----Benevent - SNRI, 2023 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 40.510.01.0