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

Preeclampsia

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
R62272
Benevent - SNRI, 2023 Gestational hypertension (blood pressure increase after the 20th week of amenorrhea), preeclampsia, eclampsia... - ICD or prescription during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.89 [1.13;3.18] 19/163   4,940/107,843 4,959 163
ref
S12526
R47189
Tran - SNRI (Controls exposed to TCA), 2022 Preeclampsia/eclampsia (gestational hypertension and a co-presence of non-infectious proteinuria) at least 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.19 [0.05;0.67] C
excluded (control group)
3/212   15/214 18 212
ref
S12527
R47195
Tran - SNRI (Controls unexposed, NOS), 2022 Preeclampsia/eclampsia (gestational hypertension and a co-presence of non-infectious proteinuria) at least 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SNRI only 0.52 [0.16;1.61] C 3/212   2,582/95,376 2,585 212
ref
S12538
R47227
Frayne - SNRI, 2021 Hypertensive disorders in pregnancy (systolic blood pressure ≥ 140 mgHg, diastolic blood pressure ≥ 90 mmHg or with features diagnostic of preeclampsia) throughout pregnancy retrospective cohort unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 2.79 [1.33;5.83] 8/31   -/255 - 31
ref
S12535
R47220
Yang - SNRI, 2021 Preeclampsia (ICD-9 or ICD-10) from the 20th week of gestation. 1st and 2nd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.96 [0.47;1.93] -/338   -/2,832 - 338
ref
S11745
R43126
Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Pre-eclampsia (ICD-9 codes 642.4x, 642.5x, 642.6x, and 642.7x) early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.12 [0.96;1.31] 171/3,059   48,599/1,447,644 48,770 3,059
ref
S12531
R47208
Bernard - SNRI, 2019 Preeclampsia (Gestational hypertension with proteinuria) or pre-existing hypertension and new or worsening proteinuria. at least 1st trimester prospective cohort unexposed, disease free Adjustment: Yes Monotherapy: no or not specified 6.46 [2.49;16.78] -/57   -/6,502 - 57
ref
S11822
R43432
Lupattelli - SNRI (Controls exposed to TCA), 2017 Late‐onset preeclampsia (any severity, mild, and severe) (developing after GW 34) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.40 [0.06;2.54] C
excluded (control group)
3/75   2/21 5 75
ref
S11823
R43433
Lupattelli - SNRI (Controls unexposed, sick), 2017 Late‐onset preeclampsia (any severity, mild, and severe) (developing after GW 34) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Monotherapy: SNRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.11 [0.35;3.56] C 3/75   184/5,093 187 75
ref
S12513
R47125
De Ocampo - SNRI, 2016 Pre-eclampsia (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on two or more consecutive readings four or more hours apart with proteinuria of 0.3 g during 24 h or more after 20 weeks of gestation) throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 3.49 [0.76;16.09] 2/21   123/3,119 125 21
ref
S11810
R43414
Avalos - SNRI (Controls exposed to TCA), 2015 Preeclampsia (ICD-9 codes occurring after 20 gestational weeks: 642.4, 642.5, 642.6, or 642.7) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 4.25 [0.80;22.54] C
excluded (control group)
5/72   2/116 7 72
ref
S11811
R43415
Avalos - SNRI (Controls unexposed, disease free), 2015 Preeclampsia (ICD-9 codes occurring after 20 gestational weeks: 642.4, 642.5, 642.6, or 642.7) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SNRI only 1.49 [0.57;3.90]
excluded (control group)
5/72   719/16,402 724 72
ref
S11812
R43416
Avalos - SNRI (Controls unexposed, sick), 2015 Preeclampsia (ICD-9 codes occurring after 20 gestational weeks: 642.4, 642.5, 642.6, or 642.7) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: SNRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.72 [0.67;4.43] C 5/72   56/1,345 61 72
ref
S11725
R43085
Palmsten a - SNRI (control exposed to TCA), 2013 Preeclampsia and/or eclampsia (ICD-9 codes 642.4x–642.7x, after 140 gestational days and within 30 days after the delivery) 2nd and/or 3rd trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.81 [0.56;1.16] C
excluded (control group)
107/1,216   47/441 154 1,216
ref
S11727
R43087
Palmsten a - SNRI (Controls unexposed, sick), 2013 Preeclampsia and/or eclampsia (ICD-9 codes 642.4x–642.7x, after 140 gestational days and within 30 days after the delivery) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.52 [1.26;1.83] 107/1,216   3,215/59,219 3,322 1,216
ref
S11795
R43396
De Vera - SNRI, 2012 Pregnancy-induced hypertension (gestational hypertension, pre-eclampsia, or eclampsia after the 20th week of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SNRI only 0.75 [0.17;3.25] 2/-   1,214/- 1,216 -
ref
S13369
R51608
Palmsten - SNRI (Controls exposed to TCA), 2012 Preeclampsia (hypertension and proteinuria occurring after the 20th week of gestation) 2nd trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.56 [0.28;1.13] C
excluded (control group)
23/408   14/146 37 408
ref
S11726
R43086
Palmsten - SNRI (Controls unexposed, sick), 2012 Preeclampsia (hypertension and proteinuria occurring after the 20th week of gestation) 2nd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.95 [1.25;3.03] 23/408   1,569/65,392 1,592 408
ref
Total 12 studies 1.58 [1.22;2.06] 62,817 5,652
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 1.89[1.13; 3.18]4,95916311%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Tran - SNRI (Controls unexposed, NOS), 2022Tran - SNRI, 2022 1 0.52[0.16; 1.61]2,5852124%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Frayne - SNRI, 2021Frayne - SNRI, 2021 2.79[1.33; 5.83]-318%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Yang - SNRI, 2021Yang - SNRI, 2021 0.96[0.47; 1.93]-3388%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine, 2020 2 1.12[0.96; 1.31]48,7703,05918%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: low Bernard - SNRI, 2019Bernard - SNRI, 2019 6.46[2.49; 16.78]-575%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Lupattelli - SNRI (Controls unexposed, sick), 2017Lupattelli - SNRI, 2017 3 1.11[0.35; 3.56]187754%ROB confusion: unclearROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate De Ocampo - SNRI, 2016De Ocampo - SNRI, 2016 3.49[0.76; 16.09]125213%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Avalos - SNRI (Controls unexposed, sick), 2015Avalos - SNRI, 2015 4 1.72[0.67; 4.43]61726%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Palmsten a - SNRI (Controls unexposed, sick), 2013Palmsten a - SNRI, 2013 5 1.52[1.26; 1.83]3,3221,21618%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate De Vera - SNRI, 2012De Vera - SNRI, 2012 0.75[0.17; 3.25]1,216-3%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Palmsten - SNRI (Controls unexposed, sick), 2012Palmsten - SNRI, 2012 6 1.95[1.25; 3.03]1,59240813%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (12 studies) I2 = 65% 1.58[1.22; 2.06]62,8175,6520.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS; 2: Controls unexposed, NOS; 3: Controls unexposed, sick; 4: Controls unexposed, sick; 5: Controls unexposed, sick; 6: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.62[1.23; 2.12]61,6015,65268%NABenevent - SNRI, 2023 Tran - SNRI (Controls unexposed, NOS), 2022 Frayne - SNRI, 2021 Yang - SNRI, 2021 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 Lupattelli - SNRI (Controls unexposed, sick), 2017 De Ocampo - SNRI, 2016 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 Palmsten - SNRI (Controls unexposed, sick), 2012 11 case control studiescase control studies 0.75[0.17; 3.28]1,216- -NADe Vera - SNRI, 2012 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.62[0.89; 2.93]57,6553,51275%NABenevent - SNRI, 2023 Tran - SNRI (Controls unexposed, NOS), 2022 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 De Ocampo - SNRI, 2016 De Vera - SNRI, 2012 6 unexposed, sickunexposed, sick 1.60[1.30; 1.95]5,1622,14011%NAFrayne - SNRI, 2021 Yang - SNRI, 2021 Lupattelli - SNRI (Controls unexposed, sick), 2017 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 Palmsten - SNRI (Controls unexposed, sick), 2012 6 Tags Adjustment   - No  - No 1.05[0.52; 2.11]2,83335921%NATran - SNRI (Controls unexposed, NOS), 2022 Lupattelli - SNRI (Controls unexposed, sick), 2017 Avalos - SNRI (Controls unexposed, sick), 2015 3   - Yes  - Yes 1.69[1.27; 2.26]59,9845,29372%NABenevent - SNRI, 2023 Frayne - SNRI, 2021 Yang - SNRI, 2021 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 De Ocampo - SNRI, 2016 Palmsten a - SNRI (Controls unexposed, sick), 2013 De Vera - SNRI, 2012 Palmsten - SNRI (Controls unexposed, sick), 2012 9 MatchedMatched 0.75[0.17; 3.28]1,216- -NADe Vera - SNRI, 2012 1 Monotherapy   - no or not specified  - no or not specified 2.52[0.45; 13.96]48,7703,11692%NAHuybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 2   - SNRI only  - SNRI only 1.58[1.26; 1.98]14,0472,53624%NABenevent - SNRI, 2023 Tran - SNRI (Controls unexposed, NOS), 2022 Frayne - SNRI, 2021 Yang - SNRI, 2021 Lupattelli - SNRI (Controls unexposed, sick), 2017 De Ocampo - SNRI, 2016 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 De Vera - SNRI, 2012 Palmsten - SNRI (Controls unexposed, sick), 2012 10 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.45[0.73; 2.87]1,59274664%NAYang - SNRI, 2021 Palmsten - SNRI (Controls unexposed, sick), 2012 2   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.57[1.32; 1.87]3,5701,3940%NAFrayne - SNRI, 2021 Lupattelli - SNRI (Controls unexposed, sick), 2017 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 4 All studiesAll studies 1.58[1.22; 2.06]62,8175,65265%NABenevent - SNRI, 2023 Tran - SNRI (Controls unexposed, NOS), 2022 Frayne - SNRI, 2021 Yang - SNRI, 2021 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 Lupattelli - SNRI (Controls unexposed, sick), 2017 De Ocampo - SNRI, 2016 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 De Vera - SNRI, 2012 Palmsten - SNRI (Controls unexposed, sick), 2012 120.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.22.30.9340.000Benevent - SNRI, 2023Tran - SNRI (Controls unexposed, NOS), 2022Frayne - SNRI, 2021Yang - SNRI, 2021Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Bernard - SNRI, 2019Lupattelli - SNRI (Controls unexposed, sick), 2017De Ocampo - SNRI, 2016Avalos - SNRI (Controls unexposed, sick), 2015Palmsten a - SNRI (Controls unexposed, sick), 2013De Vera - SNRI, 2012Palmsten - SNRI (Controls unexposed, sick), 2012

Asymetry test p-value = 0.2662 (by Egger's regression)

slope=0.1909 (0.1347); intercept=0.8389 (0.7124); t=1.1777; p=0.2662

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13369, 11725, 11810, 11811, 11822, 12526

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.59[0.95; 2.67]58,3793,58470%NABenevent - SNRI, 2023 Tran - SNRI (Controls unexposed, NOS), 2022 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bernard - SNRI, 2019 De Ocampo - SNRI, 2016 Avalos - SNRI (Controls unexposed, disease free), 2015 De Vera - SNRI, 2012 7 unexposed, sick controlsunexposed, sick controls 1.60[1.30; 1.95]5,1622,14011%NAFrayne - SNRI, 2021 Yang - SNRI, 2021 Lupattelli - SNRI (Controls unexposed, sick), 2017 Avalos - SNRI (Controls unexposed, sick), 2015 Palmsten a - SNRI (Controls unexposed, sick), 2013 Palmsten - SNRI (Controls unexposed, sick), 2012 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.65[0.33; 1.27]2211,98360%NATran - SNRI (Controls exposed to TCA), 2022 Lupattelli - SNRI (Controls exposed to TCA), 2017 Avalos - SNRI (Controls exposed to TCA), 2015 Palmsten a - SNRI (control exposed to TCA), 2013 Palmsten - SNRI (Controls exposed to TCA), 2012 50.510.01.0