Paroxetine updated on 07-01-2025

Major congenital malformations

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.
S18169
R76404		 Chan (Controls exposed to TCA), 2024 Any major malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.08 [0.36;3.25] C
excluded (control group) 		4/48   25/322 29 48
ref
S18147
R76287		 Chan (Controls unexposed, pop general), 2024 Any major malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.76 [0.63;4.90] 4/48   22,628/462,377 22,632 48
ref
S7470
R41457		 Anderson, 2020 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.45 [1.04;2.03] C 166/209   30,464/41,899 30,630 209
ref
S7434
R21901		 Bérard, 2017 Major congenital malformations overall 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.24 [0.99;1.55] -/1,132   -/14,847 - 1,132
ref
S8216
R25577		 Jordan, 2016 All major congenital anomalies 3 months or more before pregnancy or1st trimester excluded retrospective cohort (registry) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.17 [0.84;1.64]
excluded (exposition period) 		36/1,069   13,536/506,155 13,572 1,069
ref
S7521
R22544		 Ozturk, 2016 Major congenital defects at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 16.20 [2.43;108.06] C 2/12   3/246 5 12
ref
S6006
R15396		 Furu, 2015 Major birth defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.16 [0.95;1.41] 116/2,879   71,374/2,266,875 71,490 2,879
ref
S5886
R14744		 Ban (Controls unexposed, disease free), 2014 Major congenital anomalies 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.08 [0.77;1.50]
excluded (control group) 		-/1,200   8,731/325,294 - 1,200
ref
S5887
R14759		 Ban (Controls unexposed, sick), 2014 Major congenital anomalies 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.01 [0.71;1.44] -/1,200   380/13,432 - 1,200
ref
S6389
R61462		 Nordeng (Controls unexposed, NOS), 2012 Major malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.70 [0.55;5.63]
excluded (control group) 		3/76   1,550/61,648 1,553 76
ref
S7832
R61476		 Nordeng (Controls unexposed, sick), 2012 Major malformations 1st trimester cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.39 [0.42;4.68] C 3/76   30/1,048 33 76
ref
S7180
R20238		 Colvin, 2011 Any major birth defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.99 [0.65;1.51] 23/572   3,834/94,561 3,857 572
ref
S18285
R76949		 Reis (Controls exposed to TCA), 2010 Relatively severe malformation early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.87 [0.60;1.26] C
excluded (control group) 		49/1,208   77/1,662 126 1,208
ref
S18286
R76953		 Reis (Controls unexposed, NOS), 2010 Relatively severe malformation early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.20 [0.90;1.61] 49/1,208   -/1,062,190 - 1,208
ref
S5965
R15341		 Einarson, 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.26 [0.48;3.35] C 5/148   25/928 30 148
ref
S5957
R15295		 Diav-Citrin, 2008 Major anomalies 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.90 [1.09;3.33] C 19/348   40/1,359 59 348
ref
S564
R21070		 Maschi, 2008 Major malformations during pregnancy (anytime or not specified) excluded prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.00 [0.12;8.46] C
excluded (exposition period) 		1/58   6/348 7 58
ref
S6428
R17648		 Oberlander, 2008 Major congenital anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.93 [0.64;1.35] C 29/993   3,369/107,320 3,398 993
ref
S6250
R16627		 Vial, 2006 Major malformations (excluding chromosomal defects) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.40 [0.60;3.30] 12/535   10/631 22 535
ref
S6731
R19024		 Costei (Controls unexposed, NOS), 2002 Major malformations 3rd trimester prospective cohort unexposed (general population or NOS) excluded Adjustment: No Matched Monotherapy: no or not specified 0.49 [0.01;25.19] C
excluded (control group) 		0/55   0/27 0 55
ref
S6732
R19027		 Costei (Controls unexposed, sick), 2002 Major malformations 3rd trimester excluded prospective cohort unexposed, sick Adjustment: No Matched Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.49 [0.01;25.19] C
excluded (exposition period) 		0/55   0/27 0 55
ref
Total 13 studies 1.21 [1.06;1.38] 132,156 9,360
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 Chan (Controls unexposed, pop general), 2024Chan, 2024 1 1.76[0.63; 4.90]22,632482%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.45[1.04; 2.03]30,63020911%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard, 2017Bérard, 2017 1.24[0.99; 1.55]-1,13218%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ozturk, 2016Ozturk, 2016 16.20[2.43; 108.06]5120%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 1.16[0.95; 1.41]71,4902,87920%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 1.01[0.71; 1.44]-1,20010%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Nordeng (Controls unexposed, sick), 2012Nordeng, 2012 3 1.39[0.42; 4.68]33761%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 0.99[0.65; 1.51]3,8575728%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 4 1.20[0.90; 1.61]-1,20813%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Einarson, 2009Einarson, 2009 1.26[0.48; 3.35]301482%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Diav-Citrin, 2008Diav-Citrin, 2008 1.90[1.09; 3.33]593485%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Oberlander, 2008Oberlander, 2008 0.93[0.64; 1.35]3,3989939%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Vial, 2006Vial, 2006 1.40[0.60; 3.30]225352%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear Total (13 studies) I2 = 23% 1.21[1.06; 1.38]132,1569,3600.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, pop general; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.19[1.03; 1.36]101,5269,15123%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 12 case control studiescase control studies 1.45[1.04; 2.03]30,630209 -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.25[1.04; 1.50]132,1236,95238%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 10 unexposed, sickunexposed, sick 1.17[0.97; 1.42]332,4080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 1.33[0.99; 1.80]38,0342,89349%NAAnderson, 2020 Ozturk, 2016 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 8   - Yes  - Yes 1.18[1.04; 1.33]94,1226,4670%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Furu, 2015 Ban (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 5 MatchedMatched 1.40[0.60; 3.28]22535 -NAVial, 2006 1 Monotherapy   - no or not specified  - no or not specified 1.81[1.06; 3.09]1491,11935%NAOzturk, 2016 Nordeng (Controls unexposed, sick), 2012 Einarson, 2009 Diav-Citrin, 2008 Vial, 2006 5   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.24[1.08; 1.42]124,7524,2680%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 4   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.05[0.88; 1.25]7,2553,9730%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander, 2008 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.17[0.97; 1.42]332,4080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 All studiesAll studies 1.21[1.06; 1.38]132,1569,36023%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 130.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.31.1620.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard, 2017Ozturk, 2016Furu, 2015Ban (Controls unexposed, sick), 2014Nordeng (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Einarson, 2009Diav-Citrin, 2008Oberlander, 2008Vial, 2006

Asymetry test p-value = 0.0905 (by Egger's regression)

slope=0.0132 (0.1064); intercept=1.0441 (0.5627); t=1.8554; p=0.0905

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6731, 18285, 6389, 5886, 18169

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.22[1.05; 1.43]142,4388,22828%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, disease free), 2014 Nordeng (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 12 unexposed, sick controlsunexposed, sick controls 1.17[0.97; 1.42]4042,4080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.89[0.63; 1.26]1551,2560%NAChan (Controls exposed to TCA), 2024 Reis (Controls exposed to TCA), 2010 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Myles (Major congenital malformation)Myles (Major congenital malformation) 1.29[1.11; 1.49]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT8 Myles (Major congenital malformation _ Qualit ...Myles (Major congenital malformation _ Quality samples only, i.e. more than three quality points) 1.40[1.11; 1.78]3%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.18[1.05; 1.32]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT11 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.17[0.97; 1.41]0%-U,Sunexposed, sickT11st trimesterstudies TTT2 Bérard (Major congenital malformations _ Vers ...Bérard (Major congenital malformations _ Versus unexposed to any antidepressants) 1.19[1.05; 1.35]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT10 Bérard (Major congenital malformations _ Vers ...Bérard (Major congenital malformations _ Versus unexposed to paroxetine) 1.23[1.10; 1.38]2.5%-Wwhatever (meta-analysis)T11st trimesterstudies TTT15 Bérard (Major congenital malformations _ Vers ...Bérard (Major congenital malformations _ Versus unexposed to SSRIs) 1.19[1.06; 1.34]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT14 Bar-Oz (Major malformations)Bar-Oz (Major malformations) 1.30[0.93; 1.80]NA-Eexposed to other treatment, sickT11st trimesterstudies TTT4 Bar-Oz (Major malformations)Bar-Oz (Major malformations) 1.54[0.99; 2.41]NA-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT3 Bar-Oz (Major malformations)Bar-Oz (Major malformations) 1.31[1.03; 1.67]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT7 McDonagh (Major malformations)McDonagh (Major malformations) 1.17[1.02; 1.35]NA-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Grigoriadis (Major malformations (studies abo ...Grigoriadis (Major malformations (studies above quality threshold)) 1.11[0.88; 1.39]14.4%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 1.21[1.06; 1.38]23%9,360----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Diav-Citrin, 2008 Oberlander, 2008 Vial, 2006 130.510.01.0