Citalopram 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.
S18165
R76397		 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, ...) 1.70 [0.46;6.29] C
excluded (control group) 		3/53   11/322 14 53
ref
S18144
R76278		 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, ...) 1.98 [0.73;8.35] 3/53   8,107/462,377 8,110 53
ref
S13120
R50014		 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, ...) 1.57 [0.76;3.22] C
excluded (exposition period) 		19/385   13/406 32 385
ref
S7471
R22281		 Anderson, 2020 Any heart defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.27 [0.83;1.93] -/-   0/- - -
ref
S7437
R21929		 Bérard, 2017 Circulatory system 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.27 [0.81;1.99] -/584   -/14,847 - 584
ref
S6005
R15381		 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, ...) 1.15 [0.98;1.34] 176/11,193   26,745/2,266,875 26,921 11,193
ref
S7351
R21503		 Wemakor, 2015 Congenital heart defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.45 [0.79;2.65] 23/43   12,853/29,916 12,876 43
ref
S5884
R14726		 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, ...) 1.13 [0.70;1.82]
excluded (control group) 		-/1,946   2,444/325,294 - 1,946
ref
S5885
R14741		 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) 1.02 [0.61;1.70] -/1,946   112/13,432 - 1,946
ref
S6391
R61467		 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Cardiovascular malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.51 [0.48;4.77]
excluded (control group) 		3/243   541/61,648 544 243
ref
S7834
R61481		 Nordeng - Citalopram/Escitalopram (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) 1.86 [0.48;7.24] C 3/243   7/1,048 10 243
ref
S7179
R20209		 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, ...) 1.48 [0.74;2.99] 8/775   661/94,561 669 775
ref
S18283
R76942		 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, ...) 0.51 [0.32;0.84] C
excluded (control group) 		37/3,950   30/1,662 67 3,950
ref
S18284
R76946		 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, ...) 0.86 [0.62;1.20] 37/3,950   -/1,062,190 - 3,950
ref
S7003
R19862		 Merlob, 2009 Nonsyndromic congenital heart malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.46 [0.20;10.64] C 1/43   1,083/67,636 1,084 43
ref
S6425
R17641		 Oberlander a, 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, ...) 6.39 [2.02;20.21] C 3/101   512/107,320 515 101
ref
S6161
R16189		 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, ...) 0.70 [0.20;2.10] 5/20   3,719/9,564 3,724 20
ref
Total 12 studies 1.20 [1.00;1.44] 53,909 18,951
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 1.98[0.73; 8.35]8,110532%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.27[0.83; 1.93]--12%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bérard, 2017Bérard, 2017 1.27[0.81; 1.99]-58411%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 1.15[0.98; 1.34]26,92111,19329%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.45[0.79; 2.65]12,876437%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 1.02[0.61; 1.70]-1,9469%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Nordeng - Citalopram/Escitalo..., 2012 3 1.86[0.48; 7.24]102432%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.48[0.74; 2.99]6697756%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 4 0.86[0.62; 1.20]-3,95017%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Merlob, 2009Merlob, 2009 1.46[0.20; 10.64]1,084431%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Oberlander a, 2008Oberlander a, 2008 6.39[2.02; 20.21]5151012%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Louik, 2007Louik, 2007 0.70[0.20; 2.10]3,724202%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (12 studies) I2 = 27% 1.20[1.00; 1.44]53,90918,9510.220.01.0ROB: 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 1.22[0.96; 1.55]37,30918,88842%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander a, 2008 9 case control studiescase control studies 1.26[0.90; 1.76]16,600630%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.24[0.97; 1.59]53,89916,17844%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander a, 2008 Louik, 2007 9 unexposed, sickunexposed, sick 1.19[0.86; 1.65]102,7730%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 2.25[1.08; 4.69]2,2781,16236%NANordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Merlob, 2009 Oberlander a, 2008 4   - Yes  - Yes 1.13[1.00; 1.27]51,63117,7890%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 Louik, 2007 8 Monotherapy   - no or not specified  - no or not specified 1.72[0.56; 5.29]1,0942860%NANordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Merlob, 2009 2   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.19[1.04; 1.37]47,90711,8730%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, ...) 1.26[0.75; 2.12]4,9086,79267%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander a, 2008 Louik, 2007 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.10[0.68; 1.78]102,1890%NABan (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 2 All studiesAll studies 1.20[1.00; 1.44]53,90918,95127%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander a, 2008 Louik, 2007 120.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.61.2150.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard, 2017Furu, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Merlob, 2009Oberlander a, 2008Louik, 2007

Asymetry test p-value = 0.1659 (by Egger's regression)

slope=0.0266 (0.1059); intercept=0.7604 (0.5087); t=1.4946; p=0.1659

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18283, 6391, 5884, 18165

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.21[0.99; 1.48]56,90618,36731%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander a, 2008 Louik, 2007 11 unexposed, sick controlsunexposed, sick controls 1.19[0.86; 1.65]1132,7730%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.79[0.26; 2.45]814,00364%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) 1.09[0.82; 1.46]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 Kang (Cardiac malformations)Kang (Cardiac malformations) 1.03[0.84; 1.26]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT5 Myles (Cardiac malformations)Myles (Cardiac malformations) 1.03[0.80; 1.32]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT6 De Vries (Congenital Heart Defects)De Vries (Congenital Heart Defects) 1.50[0.96; 2.36]50%-Wwhatever (meta-analysis)T11st trimesterstudies TTT5 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.24[1.02; 1.51]52.5%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT11 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.08[0.75; 1.56]0%-U,Sunexposed, sickT11st trimesterstudies TTT2 metaPregmetaPreg 1.20[1.00; 1.44]27%18,951----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander a, 2008 Louik, 2007 120.510.01.0