Selective Serotonin Reuptake Inhibitor (SSRI) 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.
S12482
R47049		 Benevent, 2023 Hypertensive disorders of pregnancy (HDP) (blood pressure increase after the 20th week of amenorrhea), preeclampsia, eclampsia... - ICD or prescription at least 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.21 [0.97;1.51] 86/1,624   4,940/107,843 5,026 1,624
ref
S12517
R47150		 Tran (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: SSRI only 0.41 [0.23;0.76] C
excluded (control group) 		45/1,488   15/214 60 1,488
ref
S12516
R47144		 Tran (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: Yes Monotherapy: SSRI only 1.08 [0.81;1.44] 45/1,488   2,582/95,376 2,627 1,488
ref
S12536
R47221		 Frayne, 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: No Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.10 [0.16;7.58] 6/63   18/238 24 63
ref
S12532
R47211		 Yang, 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: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.14 [0.76;1.70] -/1,547   -/2,832 - 1,547
ref
S5461
R24122		 Levy, 2020 Preeclampsia mild or severe (diagnosed according to American College of Obstetricians and Gynecologists (ACOG) criteria) throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 7.27 [0.37;143.00] C 3/82   0/82 3 82
ref
S7914
R23952		 Palmsten, 2020 Preeclampsia (ICD-9 or 10 codes present from 140 gestational days through 14 days after delivery) 1st and 2nd trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.11 [0.96;1.29] C 354/3,804   419/4,949 773 3,804
ref
S12528
R47202		 Bernard, 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 3.09 [1.22;7.85] -/103   -/6,502 - 103
ref
S7513
R22530		 Zakiyah, 2018 Gestational hypertension (dispensed antihypertensive drugs between 20 completed weeks of gestation and 14 days after delivery) 1st and 2nd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 2.07 [1.25;3.44] -/394   571/27,481 - 394
ref
S7476
R22378		 Lupattelli (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: SSRI only 0.36 [0.08;1.65] C
excluded (control group) 		24/652   2/21 26 652
ref
S7475
R22366		 Lupattelli (Controls unexposed, sick), 2017 Late‐onset preeclampsia (any severity, mild, and severe) (developing after GW 34) 1st trimester prospective cohort unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.96 [0.63;1.46] 22/591   186/5,154 208 591
ref
S5413
R18433		 De Ocampo, 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: SSRI only 0.68 [0.24;1.90] 4/157   123/3,119 127 157
ref
S6699
R18872		 Avalos (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: SSRI only 4.22 [1.03;17.37] C
excluded (control group) 		87/1,262   2/116 89 1,262
ref
S5415
R14622		 Avalos (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: SSRI only 1.34 [1.00;1.81]
excluded (control group) 		87/1,262   719/16,402 806 1,262
ref
S13346
R51446		 Avalos (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) 1.70 [1.21;2.41] C 87/1,262   56/1,345 143 1,262
ref
S13017
R49392		 Hannerfors (Controls unexposed, NOS), 2015 Preeclampsia 1st and 2nd trimester retrospective cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 2.03 [1.01;4.07] C
excluded (control group) 		14/207   21/609 35 207
ref
S13016
R49383		 Hannerfors (Controls unexposed, sick), 2015 Preeclampsia 1st and 2nd trimester retrospective cohort unexposed, sick Adjustment: No Monotherapy: no or not specified 1.28 [0.36;4.63] C 14/207   3/56 17 207
ref
S6943
R19613		 Palmsten (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: Yes Monotherapy: SSRI only 0.61 [0.46;0.80]
excluded (control group) 		1,033/19,000   47/441 1,080 19,000
ref
S5417
R16386		 Palmsten (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: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.00 [0.93;1.07] 1,033/19,000   3,215/59,219 4,248 19,000
ref
S5414
R15262		 De Vera, 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: SSRI only 1.60 [1.00;2.55] 31/-   1,185/- 1,216 -
ref
S7000
R19856		 Palmsten (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: Yes Monotherapy: SSRI only 0.39 [0.21;0.71]
excluded (control group) 		105/3,169   14/146 119 3,169
ref
S5418
R17528		 Palmsten (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: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.22 [0.97;1.54] 105/3,169   1,569/65,392 1,674 3,169
ref
S5416
R16701		 Toh a, 2009 Gestational hypertension with preeclampsia at least 1st trimester retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 4.86 [2.70;8.76] 14/92   135/5,532 149 92
ref
S5405
R16041		 Wen, 2006 Preeclampsia 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: no or not specified 1.20 [0.90;1.61]
excluded (exposition period) 		66/972   223/3,878 289 972
ref
Total 16 studies 1.33 [1.13;1.56] 16,235 33,583
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, 2023Benevent, 2023 1.21[0.97; 1.51]5,0261,62410%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Tran (Controls unexposed, NOS), 2022Tran, 2022 1 1.08[0.81; 1.44]2,6271,4889%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Frayne, 2021Frayne, 2021 1.10[0.16; 7.58]24631%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Yang, 2021Yang, 2021 1.14[0.76; 1.70]-1,5477%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Levy, 2020Levy, 2020 7.27[0.37; 143.00]3820%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Palmsten, 2020Palmsten, 2020 1.11[0.96; 1.29]7733,80412%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bernard, 2019Bernard, 2019 3.09[1.22; 7.85]-1032%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Zakiyah, 2018Zakiyah, 2018 2.07[1.25; 3.44]-3946%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Lupattelli (Controls unexposed, sick), 2017Lupattelli, 2017 2 0.96[0.63; 1.46]2085917%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate De Ocampo, 2016De Ocampo, 2016 0.68[0.24; 1.90]1271572%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Avalos (Controls unexposed, sick), 2015Avalos, 2015 3 1.70[1.21; 2.41]1431,2628%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Hannerfors (Controls unexposed, sick), 2015Hannerfors, 2015 4 1.28[0.36; 4.63]172071%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Palmsten (Controls unexposed, sick), 2013Palmsten, 2013 5 1.00[0.93; 1.07]4,24819,00013%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate De Vera, 2012De Vera, 2012 1.60[1.00; 2.55]1,216-6%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Palmsten (Controls unexposed, sick), 2012Palmsten, 2012 6 1.22[0.97; 1.54]1,6743,16910%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Toh a, 2009Toh a, 2009 4.86[2.70; 8.76]149925%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (16 studies) I2 = 73% 1.33[1.13; 1.56]16,23533,5830.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS; 2: Controls unexposed, sick; 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 1.31[1.11; 1.55]15,01933,58373%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Frayne, 2021 Yang, 2021 Levy, 2020 Palmsten, 2020 Bernard, 2019 Zakiyah, 2018 Lupattelli (Controls unexposed, sick), 2017 De Ocampo, 2016 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 Palmsten (Controls unexposed, sick), 2012 Toh a, 2009 15 case control studiescase control studies 1.60[1.00; 2.55]1,216- -NADe Vera, 2012 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.73[1.18; 2.53]9,1483,94077%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Levy, 2020 Bernard, 2019 Zakiyah, 2018 De Ocampo, 2016 De Vera, 2012 Toh a, 2009 8 unexposed, sickunexposed, sick 1.12[1.00; 1.27]7,08729,64342%NAFrayne, 2021 Yang, 2021 Palmsten, 2020 Lupattelli (Controls unexposed, sick), 2017 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 Palmsten (Controls unexposed, sick), 2012 8 Tags Adjustment   - No  - No 1.33[0.97; 1.82]9605,41838%NAFrayne, 2021 Levy, 2020 Palmsten, 2020 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 5   - Yes  - Yes 1.35[1.10; 1.66]15,27528,16579%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Yang, 2021 Bernard, 2019 Zakiyah, 2018 Lupattelli (Controls unexposed, sick), 2017 De Ocampo, 2016 Palmsten (Controls unexposed, sick), 2013 De Vera, 2012 Palmsten (Controls unexposed, sick), 2012 Toh a, 2009 11 MatchedMatched 1.66[1.05; 2.63]1,219820%NALevy, 2020 De Vera, 2012 2 Monotherapy   - no or not specified  - no or not specified 3.46[1.95; 6.14]16948421%NALevy, 2020 Bernard, 2019 Hannerfors (Controls unexposed, sick), 2015 Toh a, 2009 4   - SNRI only  - SNRI only 1.70[1.21; 2.41]1431,262 -NAAvalos (Controls unexposed, sick), 2015 1   - SSRI only  - SSRI only 1.13[1.02; 1.26]15,92331,83740%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Frayne, 2021 Yang, 2021 Palmsten, 2020 Zakiyah, 2018 Lupattelli (Controls unexposed, sick), 2017 De Ocampo, 2016 Palmsten (Controls unexposed, sick), 2013 De Vera, 2012 Palmsten (Controls unexposed, sick), 2012 11 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.20[0.98; 1.47]1,6744,7160%NAYang, 2021 Palmsten (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) 1.12[0.95; 1.31]5,39624,72060%NAFrayne, 2021 Palmsten, 2020 Lupattelli (Controls unexposed, sick), 2017 Avalos (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 5 All studiesAll studies 1.33[1.13; 1.56]16,23533,58373%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Frayne, 2021 Yang, 2021 Levy, 2020 Palmsten, 2020 Bernard, 2019 Zakiyah, 2018 Lupattelli (Controls unexposed, sick), 2017 De Ocampo, 2016 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 De Vera, 2012 Palmsten (Controls unexposed, sick), 2012 Toh a, 2009 160.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.91.8240.000Benevent, 2023Tran (Controls unexposed, NOS), 2022Frayne, 2021Yang, 2021Levy, 2020Palmsten, 2020Bernard, 2019Zakiyah, 2018Lupattelli (Controls unexposed, sick), 2017De Ocampo, 2016Avalos (Controls unexposed, sick), 2015Hannerfors (Controls unexposed, sick), 2015Palmsten (Controls unexposed, sick), 2013De Vera, 2012Palmsten (Controls unexposed, sick), 2012Toh a, 2009

Asymetry test p-value = 0.0087 (by Egger's regression)

slope=-0.0379 (0.0594); intercept=1.6238 (0.5327); t=3.0482; p=0.0087

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7000, 6943, 6699, 5415, 13017, 7476, 12517

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.67[1.25; 2.23]10,5515,43172%NABenevent, 2023 Tran (Controls unexposed, NOS), 2022 Levy, 2020 Bernard, 2019 Zakiyah, 2018 De Ocampo, 2016 Avalos (Controls unexposed, disease free), 2015 Hannerfors (Controls unexposed, NOS), 2015 De Vera, 2012 Toh a, 2009 10 unexposed, sick controlsunexposed, sick controls 1.12[1.00; 1.27]7,08729,64342%NAFrayne, 2021 Yang, 2021 Palmsten, 2020 Lupattelli (Controls unexposed, sick), 2017 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 Palmsten (Controls unexposed, sick), 2012 8 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.57[0.35; 0.95]1,37425,57163%NATran (Controls exposed to TCA), 2022 Lupattelli (Controls exposed to TCA), 2017 Avalos (Controls exposed to TCA), 2015 Palmsten (control exposed to TCA), 2013 Palmsten (Controls exposed to TCA), 2012 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Guan - SSRI (Gestational hypertension)Guan - SSRI (Gestational hypertension) 1.14[1.00; 1.30]5.7%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 Guan - SSRI (Gestational hypertension or pree ...Guan - SSRI (Gestational hypertension or preeclampsia) 1.21[1.05; 1.40]71.3%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT7 Guan - SSRI (Preeclampsia)Guan - SSRI (Preeclampsia) 1.32[0.99; 1.78]83.3%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 1.33[1.13; 1.56]73%33,583----Benevent, 2023 Tran (Controls unexposed, NOS), 2022 Frayne, 2021 Yang, 2021 Levy, 2020 Palmsten, 2020 Bernard, 2019 Zakiyah, 2018 Lupattelli (Controls unexposed, sick), 2017 De Ocampo, 2016 Avalos (Controls unexposed, sick), 2015 Hannerfors (Controls unexposed, sick), 2015 Palmsten (Controls unexposed, sick), 2013 De Vera, 2012 Palmsten (Controls unexposed, sick), 2012 Toh a, 2009 160.510.01.0