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

Urinary 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.
S18317
R77150
Chan (Controls unexposed, sick), 2024 Urinary 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 1.32 [0.18;9.67] C 1/66   51/4,413 52 66
ref
S18315
R77126
Chan - SNRI (Controls exposed to TCA), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 2.11 [0.19;23.52] C
excluded (control group)
1/77   2/322 3 77
ref
S18316
R77138
Chan - SNRI (Controls unexposed, general pop), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SNRI only 1.29 [0.18;9.29]
excluded (control group)
1/77   3,740/462,377 3,741 77
ref
S15171
R62287
Benevent - SNRI, 2023 Urinary system anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SNRI only 0.61 [0.09;4.34] C 1/314   767/146,855 768 314
ref
S11684
R42951
Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021 Urinary malformations (Q61, Q62, Q63, Q64, Q794) 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.19 [0.54;2.63]
excluded (control group)
8/1,438   27/5,751 35 1,438
ref
S11685
R42967
Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Urinary malformations (Q61, Q62, Q63, Q64, Q794) 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) 1.33 [0.46;3.84] 8/1,434   6/1,435 14 1,434
ref
S11745
R43136
Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Urinary malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.89 [1.14;3.14]
excluded (control group)
-/2,532   -/- - 2,532
ref
S11746
R43150
Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Urinary 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) 1.11 [0.52;2.36] -/2,532   -/2,456 - 2,532
ref
S11696
R43030
Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Urinary 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) 1.43 [0.75;2.73] -/738   -/14,847 - 738
ref
Total 5 studies 1.25 [0.82;1.91] 834 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 1.32[0.18; 9.67]52665%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Benevent - SNRI, 2023Benevent - SNRI, 2023 0.61[0.09; 4.34]7683145%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Ankarfeldt a - Duloxetine, 2021 2 1.33[0.46; 3.84]141,43416%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: low Huybrechts - Duloxetine (Controls unexposed, sick), 2020Huybrechts - Duloxetine, 2020 3 1.11[0.52; 2.36]-2,53232%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 1.43[0.75; 2.73]-73843%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.25[0.82; 1.91]8345,0840.25.01.0ROB: 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 1.25[0.82; 1.91]8345,0840%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) 0.61[0.09; 4.34]768314 -NABenevent - SNRI, 2023 1 unexposed, sickunexposed, sick 1.29[0.84; 2.00]664,7700%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 0.89[0.22; 3.61]8203800%NAChan (Controls unexposed, sick), 2024 Benevent - SNRI, 2023 2   - Yes  - Yes 1.29[0.83; 2.02]144,7040%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 1.18[0.64; 2.18]143,9660%NAAnkarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 2   - SNRI only  - SNRI only 1.32[0.71; 2.43]7681,0520%NABenevent - SNRI, 2023 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 2   - SSRI only  - SSRI only 1.32[0.18; 9.67]5266 -NAChan (Controls unexposed, sick), 2024 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.29[0.83; 2.02]144,7040%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 1.32[0.18; 9.67]5266 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.25[0.82; 1.91]8345,0840%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 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.61.2210.000Chan (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 = 0.3271 (by Egger's regression)

slope=0.4691 (0.2304); intercept=-0.5555 (0.4755); t=1.1683; p=0.3271

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) 1.57[1.04; 2.35]4,5444,3610%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 1.29[0.84; 2.00]664,7700%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 2.11[0.19; 23.52]377 -NAChan - SNRI (Controls exposed to TCA), 2024 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SNRIs (Congenital anomalies of the ki ...Huang - SNRIs (Congenital anomalies of the kidney and urinary tract) 1.72[1.25; 2.35]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Lou - SNRIs (Urinary malformations)Lou - SNRIs (Urinary malformations) 1.20[0.70; 2.07]0%-Eexposed to other treatment, sickT11st trimesterstudies TTT2 Lou - SNRIs (Urinary malformations)Lou - SNRIs (Urinary malformations) 1.29[0.83; 2.02]0%-U,Sunexposed, sickT11st trimesterstudies TTT3 Lou - SNRIs (Urinary malformations)Lou - SNRIs (Urinary malformations) 1.50[0.99; 2.25]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT2 metaPregmetaPreg 1.25[0.82; 1.91]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