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

Early intrauterine deaths (< 22 weeks) / Spontaneous abortions

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.
S11686
R42970		 Ankarfeldt b - Duloxetine (Controls unexposed, NOS), 2021 Spontaneous abortions (< 22 weeks of pregnancy) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.14 [0.96;1.34]
excluded (control group) 		143/1,197   103,367/987,200 103,510 1,197
ref
S11687
R42972		 Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Spontaneous abortions (< 22 weeks of pregnancy) during pregnancy (anytime or not specified) 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) 1.04 [0.83;1.30] 143/1,197   163/1,376 306 1,197
ref
S11774
R43308		 Richardson - Venlafaxine, 2019 Spontaneous abortion (prior to 24 weeks which did not result in elective termination) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: no or not specified 1.26 [0.83;1.91] 46/219   140/965 186 219
ref
S11791
R43386		 Ozturk - Venlafaxine, 2016 Miscarriages at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.75 [0.04;13.48] C 0/11   15/261 15 11
ref
S11776
R43329		 Te Winkel - Venlafaxine, 2016 Spontaneous abortions during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.94 [1.33;2.82] C 85/732   46/724 131 732
ref
S11806
R43410		 Kjaersgaard - Venlafaxine (Controls unexposed, NOS), 2013 Spontaneous abortion (before 22 weeks of gestation) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.71 [1.50;1.95]
excluded (control group) 		-/-   -/983,258 - -
ref
S11808
R43412		 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Spontaneous abortion (before 22 weeks of gestation) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.80 [1.19;2.72] -/-   -/- - -
ref
S11699
R43050		 Nakhai-Pour - Venlafaxine, 2010 Spontaneous abortions (< 20th week of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SNRI only 2.11 [1.34;3.30] 33/-   5,091/- 5,124 -
ref
S11765
R43214		 Yaris - Venlafaxine, 2005 Spontaneous abortions during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.20 [0.07;21.95] C 0/11   9/248 9 11
ref
S11755
R43202		 Einarson - Venlafaxine, 2001 Spontaneous abortion at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.72 [0.78;3.79] C 18/150   11/150 29 150
ref
Total 8 studies 1.53 [1.18;1.98] 5,800 2,320
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 Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021Ankarfeldt b - Duloxetine, 2021 1 1.04[0.83; 1.30]3061,19724%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: low Richardson - Venlafaxine, 2019Richardson - Venlafaxine, 2019 1.26[0.83; 1.91]18621917%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Ozturk - Venlafaxine, 2016Ozturk - Venlafaxine, 2016 0.75[0.04; 13.48]15111%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Te Winkel - Venlafaxine, 2016Te Winkel - Venlafaxine, 2016 1.94[1.33; 2.82]13173218%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013Kjaersgaard - Venlafaxine, 2013 2 1.80[1.19; 2.72]--17%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Nakhai-Pour - Venlafaxine, 2010Nakhai-Pour - Venlafaxine, 2010 2.11[1.34; 3.30]5,124-15%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Yaris - Venlafaxine, 2005Yaris - Venlafaxine, 2005 1.20[0.07; 21.95]9111%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Einarson - Venlafaxine, 2001Einarson - Venlafaxine, 2001 1.72[0.78; 3.79]291508%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (8 studies) I2 = 53% 1.53[1.18; 1.98]5,8002,3200.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.43[1.10; 1.86]6762,32046%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Richardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 7 case control studiescase control studies 2.11[1.34; 3.31]5,124- -NANakhai-Pour - Venlafaxine, 2010 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.71[1.37; 2.15]5,4941,1230%NARichardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Nakhai-Pour - Venlafaxine, 2010 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 6 unexposed, sickunexposed, sick 1.33[0.78; 2.27]3061,19781%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 2 Tags Adjustment   - No  - No 1.84[1.42; 2.38]1849040%NAOzturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 5   - Yes  - Yes 1.36[0.90; 2.03]5,6161,41674%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Richardson - Venlafaxine, 2019 Nakhai-Pour - Venlafaxine, 2010 3 MatchedMatched 1.62[0.98; 2.68]5,31021963%NARichardson - Venlafaxine, 2019 Nakhai-Pour - Venlafaxine, 2010 2 Monotherapy   - no or not specified  - no or not specified 1.43[1.10; 1.86]6762,32046%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Richardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 7   - SNRI only  - SNRI only 2.11[1.34; 3.31]5,124- -NANakhai-Pour - Venlafaxine, 2010 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.33[0.78; 2.27]3061,19781%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 2 All studiesAll studies 1.53[1.18; 1.98]5,8002,32053%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Richardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Nakhai-Pour - Venlafaxine, 2010 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 80.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.91.7820.000Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021Richardson - Venlafaxine, 2019Ozturk - Venlafaxine, 2016Te Winkel - Venlafaxine, 2016Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013Nakhai-Pour - Venlafaxine, 2010Yaris - Venlafaxine, 2005Einarson - Venlafaxine, 2001

Asymetry test p-value = 0.4308 (by Egger's regression)

slope=0.1748 (0.2119); intercept=0.8352 (0.9891); t=0.8444; p=0.4308

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 11806, 11686

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.55[1.24; 1.93]109,0042,34464%NAAnkarfeldt b - Duloxetine (Controls unexposed, NOS), 2021 Richardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, NOS), 2013 Nakhai-Pour - Venlafaxine, 2010 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 8 unexposed, sick controlsunexposed, sick controls 1.33[0.78; 2.27]3061,19781%NAAnkarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Smith - SNRI (Miscarriage (spontaneous aborti ...Smith - SNRI (Miscarriage (spontaneous abortion, defined as pregnancy loss before viability)) 1.19[1.02; 1.39]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Smith - SNRI (Miscarriage (spontaneous aborti ...Smith - SNRI (Miscarriage (spontaneous abortion, defined as pregnancy loss before viability)) 1.42[1.11; 1.81]47%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 1.53[1.18; 1.98]53%2,320----Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021 Richardson - Venlafaxine, 2019 Ozturk - Venlafaxine, 2016 Te Winkel - Venlafaxine, 2016 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Nakhai-Pour - Venlafaxine, 2010 Yaris - Venlafaxine, 2005 Einarson - Venlafaxine, 2001 80.510.01.0