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

Postpartum hemorrhage

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.
S18440
R78228
Lee (Controls exposed to TCAs), 2025 Postpartum haemorrhage during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 1.86 [0.69;5.04] C
excluded (control group)
5/71   24/613 29 71
ref
S18441
R78249
Lee (Controls unexposed, general pop), 2025 Postpartum haemorrhage during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.40 [0.56;3.49] 5/71   19,755/463,440 19,760 71
ref
S18335
R77359
Jackson - SNRI, 2024 Post-partum hemorrhage (ICD-10 diagnosis code for PPH and a procedure code for blood transfusion) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Monotherapy: SNRI only 2.14 [0.89;4.34] 7/145   3,124/106,961 3,131 145
ref
S11745
R43128
Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Postpartum hemorrhage (ICD-9 diagnostic codes 666.xx) late pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.53 [1.08;2.18] 34/955   95,988/4,128,460 96,022 955
ref
S11741
R43097
Hanley - SNRI, 2016 Postpartum hemorrhage late pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.64 [1.38;1.96] 154/1,390   21,745/310,813 21,899 1,390
ref
S11738
R43094
Palmsten b - SNRI, 2013 Postpartum hemorrhage (ICD-9 code for 666.x) late pregnancy retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SNRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.90 [1.37;2.63] 35/702   1,896/69,044 1,931 702
ref
Total 5 studies 1.67 [1.46;1.92] 142,743 3,263
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 Lee (Controls unexposed, general pop), 2025Lee, 2025 1 1.40[0.56; 3.49]19,760712%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Jackson - SNRI, 2024Jackson - SNRI, 2024 2.14[0.89; 4.34]3,1311453%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine, 2020 2 1.53[1.08; 2.18]96,02295515%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Hanley - SNRI, 2016Hanley - SNRI, 2016 1.64[1.38; 1.96]21,8991,39062%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Palmsten b - SNRI, 2013Palmsten b - SNRI, 2013 1.90[1.37; 2.63]1,93170218%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.67[1.46; 1.92]142,7433,2630.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.67[1.46; 1.92]142,7433,2630%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 Palmsten b - SNRI, 2013 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.63[1.40; 1.89]140,8122,5610%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 4 unexposed, sickunexposed, sick 1.90[1.37; 2.63]1,931702 -NAPalmsten b - SNRI, 2013 1 Tags Adjustment   - Yes  - Yes 1.67[1.46; 1.92]142,7433,2630%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 Palmsten b - SNRI, 2013 5 Monotherapy   - no or not specified  - no or not specified 1.53[1.08; 2.17]96,022955 -NAHuybrechts - Duloxetine (Controls unexposed, NOS), 2020 1   - SNRI only  - SNRI only 1.70[1.46; 1.97]46,7212,3080%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Hanley - SNRI, 2016 Palmsten b - SNRI, 2013 4 Unexposed sick   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.90[1.37; 2.63]1,931702 -NAPalmsten b - SNRI, 2013 1 All studiesAll studies 1.67[1.46; 1.92]142,7433,2630%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 Palmsten b - SNRI, 2013 50.55.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.11.60.5600.000Lee (Controls unexposed, general pop), 2025Jackson - SNRI, 2024Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Hanley - SNRI, 2016Palmsten b - SNRI, 2013

Asymetry test p-value = 0.7483 (by Egger's regression)

slope=0.4869 (0.0921); intercept=0.2062 (0.5863); t=0.3517; p=0.7483

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18440

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.63[1.40; 1.89]140,8122,5610%NALee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 4 unexposed, sick controlsunexposed, sick controls 1.90[1.37; 2.63]1,931702 -NAPalmsten b - SNRI, 2013 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.86[0.69; 5.04]2971 -NALee (Controls exposed to TCAs), 2025 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Jiang (Postpartum hemorrhage)Jiang (Postpartum hemorrhage) 1.62[1.41; 1.85]23.7%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 1.67[1.46; 1.92]0%3,263----Lee (Controls unexposed, general pop), 2025 Jackson - SNRI, 2024 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Hanley - SNRI, 2016 Palmsten b - SNRI, 2013 50.510.01.0