Selective Serotonin Reuptake Inhibitor (SSRI) updated on 07-01-2025

Elective/induced termination of pregnancy

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.
S7479
R22385		 Richardson, 2019 Elective termination of pregnancy during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.16 [0.85;1.59] C 71/843   103/1,405 174 843
ref
S7518
R22533		 Ozturk - Escitalopram, 2016 Elective termination of pregnancy at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.75 [0.48;6.41] C 3/35   14/275 17 35
ref
S9999
R36005		 Kieler, 2015 Elective termination of pregnancy (at 12–23 weeks of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SSRI only 1.60 [1.40;1.70] -/-   14,911/- - -
ref
S11224
R41302		 Ban (Controls exposed to TCA), 2012 Termination of pregnancy during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.43 [1.31;1.57] C
excluded (control group) 		3,090/14,191   708/4,349 3,798 14,191
ref
S11225
R41305		 Ban (Controls unexposed, disease free), 2012 Termination of pregnancy during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 2.20 [2.10;2.40]
excluded (control group) 		3,090/14,191   -/- - 14,191
ref
S11226
R41308		 Ban (Controls unexposed, sick), 2012 Termination of pregnancy during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 2.00 [1.80;2.30] 3,090/14,191   -/- - 14,191
ref
S7579
R23156		 Manakova, 2011 Elective abortions (ETOP) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 8.69 [1.80;42.00] C 9/52   2/85 11 52
ref
S5958
R15301		 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Elective termination of pregnancy (ETOP) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.14 [1.40;3.25] C 49/809   43/1,467 92 809
ref
S507
R16620		 Vial - Paroxetine, 2006 Voluntary abortion 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 3.10 [1.90;5.40] 61/683   20/683 81 683
ref
S6197
R16358		 Pastuszak - Fluoxetine (Controls exposed to TCA), 1993 Elective abortions 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: SSRI only 1.22 [0.35;4.18] C
excluded (control group) 		6/74   5/74 11 74
ref
S515
R16348		 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 Elective abortions 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 1.41 [0.55;3.63] C 11/128   8/128 19 128
ref
Total 8 studies 1.82 [1.48;2.24] 394 16,741
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 Richardson, 2019Richardson, 2019 1.16[0.85; 1.59]17484317%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Ozturk - Escitalopram, 2016Ozturk - Escitalopram, 2016 1.75[0.48; 6.41]17352%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Kieler, 2015Kieler, 2015 1.60[1.40; 1.70]--27%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2012Ban, 2012 1 2.00[1.80; 2.30]-14,19126%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Manakova, 2011Manakova, 2011 8.69[1.80; 42.00]11522%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Diav-Citrin - Fluoxetine or Paroxetine, 2008Diav-Citrin - Fluoxetine or Paroxetine, 2008 2.14[1.40; 3.25]9280913%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Vial - Paroxetine, 2006Vial - Paroxetine, 2006 3.10[1.90; 5.40]8168310%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993Pastuszak - Fluoxetine, 1993 2 1.41[0.55; 3.63]191284%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 71% 1.82[1.48; 2.24]39416,7410.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.95[1.44; 2.65]39416,74166%NARichardson, 2019 Ozturk - Escitalopram, 2016 Ban (Controls unexposed, sick), 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 7 case control studiescase control studies 1.60[1.45; 1.76]-- -NAKieler, 2015 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.82[1.36; 2.43]3942,55063%NARichardson, 2019 Ozturk - Escitalopram, 2016 Kieler, 2015 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 7 unexposed, sickunexposed, sick 2.00[1.77; 2.26]-14,191 -NABan (Controls unexposed, sick), 2012 1 Tags Adjustment   - No  - No 2.02[1.26; 3.23]3942,55069%NARichardson, 2019 Ozturk - Escitalopram, 2016 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 6   - Yes  - Yes 1.78[1.43; 2.22]-14,19187%NAKieler, 2015 Ban (Controls unexposed, sick), 2012 2 MatchedMatched 1.94[1.20; 3.12]10081167%NAKieler, 2015 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 3 Monotherapy   - no or not specified  - no or not specified 2.16[1.26; 3.71]3752,42275%NARichardson, 2019 Ozturk - Escitalopram, 2016 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 5   - SSRI only  - SSRI only 1.76[1.44; 2.16]1914,31975%NAKieler, 2015 Ban (Controls unexposed, sick), 2012 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 3 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 2.00[1.77; 2.26]-14,191 -NABan (Controls unexposed, sick), 2012 1 All studiesAll studies 1.82[1.48; 2.24]39416,74171%NARichardson, 2019 Ozturk - Escitalopram, 2016 Kieler, 2015 Ban (Controls unexposed, sick), 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 80.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.62.60.9650.000Richardson, 2019Ozturk - Escitalopram, 2016Kieler, 2015Ban (Controls unexposed, sick), 2012Manakova, 2011Diav-Citrin - Fluoxetine or Paroxetine, 2008Vial - Paroxetine, 2006Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993

Asymetry test p-value = 0.4964 (by Egger's regression)

slope=0.5012 (0.1011); intercept=0.7065 (0.9761); t=0.7238; p=0.4964

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6197, 11224, 11225

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.89[1.50; 2.39]18,37716,74185%NARichardson, 2019 Ozturk - Escitalopram, 2016 Kieler, 2015 Ban (Controls unexposed, disease free), 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Vial - Paroxetine, 2006 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 8 unexposed, sick controlsunexposed, sick controls 2.00[1.77; 2.26]3,08114,191 -NABan (Controls unexposed, sick), 2012 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.43[1.31; 1.56]3,80914,2650%NABan (Controls exposed to TCA), 2012 Pastuszak - Fluoxetine (Controls exposed to TCA), 1993 20.510.01.0