Paroxetine updated on 07-01-2025

Congenital heart defects

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
R76405		 Chan (Controls exposed to TCA), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.60 [0.08;4.77] C
excluded (control group) 		1/48   11/322 12 48
ref
S18147
R76288		 Chan (Controls unexposed, pop general), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.19 [0.16;8.61] 1/48   8,107/462,377 8,108 48
ref
S13126
R50050		 Marks (Controls exposed to Bupropion), 2021 Cardiac Malformations during pregnancy (anytime or not specified) excluded retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 2.37 [0.74;7.55] C
excluded (exposition period) 		4/55   13/406 17 55
ref
S7470
R22239		 Anderson, 2020 Any heart defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.52 [1.04;2.23] -/-   0/- - -
ref
S7434
R21891		 Bérard, 2017 Circulatory system 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) 1.13 [0.79;1.60] -/1,132   -/14,847 - 1,132
ref
S6006
R15397		 Furu, 2015 Any cardiac defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.30 [0.96;1.75] 53/2,879   26,745/2,266,875 26,798 2,879
ref
S7350
R21477		 Wemakor, 2015 Congenital heart defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.53 [0.91;2.58] 31/58   12,845/29,901 12,876 58
ref
S5886
R14745		 Ban (Controls unexposed, disease free), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.78 [1.09;2.88]
excluded (control group) 		-/1,200   2,444/325,294 - 1,200
ref
S5887
R14760		 Ban (Controls unexposed, sick), 2014 Heart congenital malformations 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) 1.67 [1.00;2.80] -/1,200   112/13,432 - 1,200
ref
S6100
R15916		 Huybrechts (Controls unexposed, NOS), 2014 Any cardiac malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.16 [0.94;1.42]
excluded (control group) 		93/11,126   6,403/885,115 6,496 11,126
ref
S6101
R15920		 Huybrechts (Controls unexposed, sick), 2014 Any cardiac malformations 1st trimester cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 0.93 [0.72;1.19] 71/8,756   1,497/180,564 1,568 8,756
ref
S6389
R61463		 Nordeng (Controls unexposed, NOS), 2012 Cardiovascular malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.51 [0.21;10.85] C
excluded (control group) 		1/76   541/61,648 542 76
ref
S7832
R61477		 Nordeng (Controls unexposed, sick), 2012 Cardiovascular 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) 1.98 [0.24;16.33] C 1/76   7/1,048 8 76
ref
S7180
R20242		 Colvin, 2011 Cardiovascular 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, ...) 1.76 [0.83;3.72] 7/572   661/94,561 668 572
ref
S18285
R76950		 Reis (Controls exposed to TCA), 2010 Any cardiovascular defect 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, ...) 1.10 [0.64;1.90] C
excluded (control group) 		24/1,208   30/1,662 54 1,208
ref
S18286
R76954		 Reis (Controls unexposed, NOS), 2010 Any cardiovascular defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.66 [1.09;2.53] 24/1,208   -/1,062,190 - 1,208
ref
S6418
R17628		 Merlob, 2009 Nonsyndromic congenital heart malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.79 [1.02;7.62] C 4/92   1,083/67,636 1,087 92
ref
S5957
R15297		 Diav-Citrin, 2008 Major cardiovascular anomalies 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.66 [0.80;8.90] 7/348   8/1,359 15 348
ref
S7244
R21006		 Einarson, 2008 Cardiovascular defects 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.10 [0.36;2.78] 9/1,174   -/- - 1,174
ref
S564
R21071		 Maschi, 2008 Cardiac malformations during pregnancy (anytime or not specified) excluded prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 18.45 [0.74;458.58] C
excluded (exposition period) 		1/58   0/348 1 58
ref
S6428
R17649		 Oberlander, 2008 Cardiovascular congenital 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, ...) 1.48 [0.70;3.13] C 7/993   512/107,320 519 993
ref
S7228
R41662		 Davis, 2007 Congenital anomalies of heart 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.92 [0.34;2.48] C 4/182   1,184/49,654 1,188 182
ref
S6160
R16171		 Louik, 2007 Any cardiac defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.40 [0.80;2.50] 25/55   3,699/9,529 3,724 55
ref
S6250
R16628		 Vial, 2006 Major cardiac defects 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.18 [0.24;5.87] C 3/535   3/631 6 535
ref
Total 17 studies 1.29 [1.14;1.46] 56,565 19,308
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 1.19[0.16; 8.61]8,108480%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.52[1.04; 2.23]--10%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard, 2017Bérard, 2017 1.13[0.79; 1.60]-1,13212%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 1.30[0.96; 1.75]26,7982,87917%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.53[0.91; 2.58]12,876586%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 1.67[1.00; 2.80]-1,2006%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Huybrechts (Controls unexposed, sick), 2014Huybrechts, 2014 3 0.93[0.72; 1.19]1,5688,75624%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Nordeng (Controls unexposed, sick), 2012Nordeng, 2012 4 1.98[0.24; 16.33]8760%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.76[0.83; 3.72]6685723%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 5 1.66[1.09; 2.53]-1,2089%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Merlob, 2009Merlob, 2009 2.79[1.02; 7.62]1,087922%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Diav-Citrin, 2008Diav-Citrin, 2008 2.66[0.80; 8.90]153481%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Einarson, 2008Einarson, 2008 1.10[0.36; 2.78]-1,1741%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Oberlander, 2008Oberlander, 2008 1.48[0.70; 3.13]5199933%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Davis, 2007Davis, 2007 0.92[0.34; 2.48]1,1881822%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Louik, 2007Louik, 2007 1.40[0.80; 2.50]3,724555%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Vial, 2006Vial, 2006 1.18[0.24; 5.87]65351%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear Total (17 studies) I2 = 0% 1.29[1.14; 1.46]56,56519,3080.210.01.0ROB: 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, sick; 5: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.27[1.09; 1.48]39,96519,1959%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Furu, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Oberlander, 2008 Davis, 2007 Vial, 2006 14 case control studiescase control studies 1.49[1.14; 1.96]16,6001130%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.47[1.25; 1.73]54,9898,1440%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Oberlander, 2008 Davis, 2007 Louik, 2007 Vial, 2006 13 unexposed, sickunexposed, sick 1.13[0.86; 1.47]1,57611,16433%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 Tags Adjustment   - No  - No 1.51[1.04; 2.20]3,4763,6240%NANordeng (Controls unexposed, sick), 2012 Colvin, 2011 Merlob, 2009 Einarson, 2008 Oberlander, 2008 Davis, 2007 Vial, 2006 7   - Yes  - Yes 1.31[1.11; 1.53]53,08915,68424%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 Diav-Citrin, 2008 Louik, 2007 10 MatchedMatched 1.18[0.24; 5.87]6535 -NAVial, 2006 1 Monotherapy   - no or not specified  - no or not specified 1.19[0.83; 1.69]3,87211,16317%NAHuybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Davis, 2007 Vial, 2006 7   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.32[1.10; 1.59]47,7824,1170%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 5   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.60[1.25; 2.05]4,9114,0280%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander, 2008 Louik, 2007 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.29[0.97; 1.72]82,4080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 0.93[0.72; 1.20]1,5688,756 -NAHuybrechts (Controls unexposed, sick), 2014 1 All studiesAll studies 1.29[1.14; 1.46]56,56519,3080%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Oberlander, 2008 Davis, 2007 Louik, 2007 Vial, 2006 170.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.52.81.2910.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard, 2017Furu, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Huybrechts (Controls unexposed, sick), 2014Nordeng (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Merlob, 2009Diav-Citrin, 2008Einarson, 2008Oberlander, 2008Davis, 2007Louik, 2007Vial, 2006

Asymetry test p-value = 0.0580 (by Egger's regression)

slope=0.0555 (0.1115); intercept=0.8848 (0.4311); t=2.0524; p=0.0580

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18285, 6389, 5886, 6100, 18169

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.37[1.21; 1.55]64,47720,5460%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, NOS), 2014 Nordeng (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Oberlander, 2008 Davis, 2007 Louik, 2007 Vial, 2006 16 unexposed, sick controlsunexposed, sick controls 1.13[0.86; 1.47]1,67911,16433%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.06[0.63; 1.79]661,2560%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 Viswanathan (Cardiac anomalies)Viswanathan (Cardiac anomalies) 1.26[0.96; 1.65]59%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 Wurst (Cardiac defects)Wurst (Cardiac defects) 1.46[1.17; 1.82]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT14 Bar-Oz (Cardiac malformations)Bar-Oz (Cardiac malformations) 1.72[1.22; 2.42]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT6 Bar-Oz (Cardiac malformations)Bar-Oz (Cardiac malformations) 1.70[1.17; 2.46]NA-Eexposed to other treatment, sickT11st trimesterstudies TTT4 Bar-Oz (Cardiac malformations)Bar-Oz (Cardiac malformations) 3.47[0.90; 12.21]NA-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT3 McDonagh (Cardiac malformations)McDonagh (Cardiac malformations) 1.49[1.20; 1.85]NA-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Myles (Cardiac malformations)Myles (Cardiac malformations) 1.44[1.12; 1.86]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT8 O'Brien (Cardiac malformations _ Case control ...O'Brien (Cardiac malformations _ Case control studies) 1.18[0.88; 1.59]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT3 Bérard (Cardiac malformations _ Versus unexpo ...Bérard (Cardiac malformations _ Versus unexposed to any antidepressants) 1.23[1.06; 1.43]1.0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT13 Bérard (Cardiac malformations _ Versus unexpo ...Bérard (Cardiac malformations _ Versus unexposed to paroxetine) 1.28[1.11; 1.47]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT18 Bérard (Cardiac malformations _ Versus unexpo ...Bérard (Cardiac malformations _ Versus unexposed to SSRIs) 1.27[1.10; 1.47]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT17 Painuly (Cardiovascular malformations)Painuly (Cardiovascular malformations) 1.25[1.01; 1.54]30%-Wwhatever (meta-analysis)T11st trimesterstudies TTT11 Grigoriadis (Cardiovascular malformations (st ...Grigoriadis (Cardiovascular malformations (studies above quality threshold)) 1.43[1.08; 1.88]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT7 Painuly (Cardiovascular malformations _ Case- ...Painuly (Cardiovascular malformations _ Case-control studies) 1.09[0.91; 1.30]-Wwhatever (meta-analysis)T11st trimesterstudies TTT-9 Painuly (Cardiovascular malformations _ Cohor ...Painuly (Cardiovascular malformations _ Cohort studies) 1.52[0.98; 2.34]-Wwhatever (meta-analysis)T11st trimesterstudies TTT-9 De Vries (Congenital Heart Defects)De Vries (Congenital Heart Defects) 1.57[1.25; 1.97]37%-Wwhatever (meta-analysis)T11st trimesterstudies TTT9 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.27[0.89; 1.80]72.3%-U,Sunexposed, sickT11st trimesterstudies TTT3 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.35[1.19; 1.53]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT16 metaPregmetaPreg 1.29[1.14; 1.46]0%19,308----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Einarson, 2008 Oberlander, 2008 Davis, 2007 Louik, 2007 Vial, 2006 170.510.01.0