Citalopram updated on 07-01-2025

All congenital malformations (majors, minors, majors and minors, or unspecified)

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
R76417		 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, ...) 1.24 [0.45;3.39] C
excluded (control group) 		5/53   25/322 30 53
ref
S18144
R76418		 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, ...) 1.86 [0.68;5.09] 5/53   22,628/462,377 22,633 53
ref
S7471
R41460		 Anderson, 2020 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.21 [0.85;1.74] C 126/165   30,504/41,943 30,630 165
ref
S7437
R23470		 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) 1.36 [1.08;1.73] -/584   -/14,847 - 584
ref
S8214
R25534		 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 1.16 [0.98;1.38]
excluded (exposition period) 		136/4,028   13,536/506,155 13,672 4,028
ref
S7527
R23475		 Ozturk, 2016 Major congenital defects at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 23.10 [0.79;671.66] C 0/2   3/246 3 2
ref
S6005
R23473		 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, ...) 1.19 [1.07;1.31] 446/11,193   71,374/2,266,875 71,820 11,193
ref
S5884
R23468		 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, ...) 1.06 [0.80;1.40]
excluded (control group) 		-/1,946   8,731/325,294 - 1,946
ref
S5885
R23469		 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) 0.97 [0.71;1.31] -/1,946   380/13,432 - 1,946
ref
S6391
R17405		 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Any malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.47 [0.88;2.46]
excluded (control group) 		16/243   2,829/61,648 2,845 243
ref
S7834
R23257		 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Any 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) 1.23 [0.69;2.17] C 16/243   57/1,048 73 243
ref
S7179
R23472		 Colvin, 2011 Any 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, ...) 1.36 [1.02;1.81] 50/775   4,571/94,561 4,621 775
ref
S18283
R76944		 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, ...) 0.72 [0.54;0.96] C
excluded (control group) 		133/3,950   77/1,662 210 3,950
ref
S18284
R76948		 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, ...) 1.06 [0.88;1.26] 133/3,950   -/1,062,190 - 3,950
ref
S5962
R23471		 Einarson, 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.64 [0.73;3.70] C 8/184   25/928 33 184
ref
S6425
R23474		 Oberlander a, 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, ...) 1.27 [0.47;3.46] C 4/101   3,369/107,320 3,373 101
ref
S6415
R23476		 Sivojelezova (Control exposed to other SSRI), 2005 Major malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: no or not specified 0.35 [0.04;3.41] C
excluded (control group) 		1/108   3/115 4 108
ref
S6414
R23477		 Sivojelezova (Control unexposed, NOS), 2005 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.09 [0.07;17.70] C 1/108   1/118 2 108
ref
S18303
R77080		 Heikkinen, 2002 Malformations throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.00 [0.02;55.80] C 0/10   0/10 0 10
ref
Total 13 studies 1.19 [1.10;1.28] 133,188 19,314
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 1.86[0.68; 5.09]22,633531%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.21[0.85; 1.74]30,6301654%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bérard, 2017Bérard, 2017 1.36[1.08; 1.73]-58410%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ozturk, 2016Ozturk, 2016 23.10[0.79; 671.66]320%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 1.19[1.07; 1.31]71,82011,19353%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 0.97[0.71; 1.31]-1,9466%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Nordeng - Citalopram/Escitalo..., 2012 3 1.23[0.69; 2.17]732432%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.36[1.02; 1.81]4,6217757%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 4 1.06[0.88; 1.26]-3,95017%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Einarson, 2009Einarson, 2009 1.64[0.73; 3.70]331841%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Oberlander a, 2008Oberlander a, 2008 1.27[0.47; 3.46]3,3731011%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Sivojelezova (Control unexposed, NOS), 2005Sivojelezova, 2005 5 1.09[0.07; 17.70]21080%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Heikkinen, 2002Heikkinen, 2002 1.00[0.02; 55.80]0100%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (13 studies) I2 = 0% 1.19[1.10; 1.28]133,18819,3140.250.01.0ROB: 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; 5: Control unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.19[1.10; 1.28]102,55819,1490%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 12 case control studiescase control studies 1.21[0.85; 1.74]30,630165 -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.19[1.09; 1.29]133,11516,5410%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 10 unexposed, sickunexposed, sick 1.18[0.94; 1.49]732,77332%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 1.32[1.08; 1.61]38,7351,5880%NAAnderson, 2020 Ozturk, 2016 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 8   - Yes  - Yes 1.16[1.05; 1.29]94,45317,72621%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Furu, 2015 Ban (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 5 MatchedMatched 1.06[0.11; 10.48]21180%NASivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 2 Monotherapy   - no or not specified  - no or not specified 1.41[0.89; 2.22]1115470%NAOzturk, 2016 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 5   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.22[1.11; 1.33]125,08311,9950%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, ...) 1.10[0.97; 1.26]7,9946,7720%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander a, 2008 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.18[0.94; 1.49]732,77332%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 All studiesAll studies 1.19[1.10; 1.28]133,18819,3140%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 130.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.02.4620.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard, 2017Ozturk, 2016Furu, 2015Ban (Controls unexposed, sick), 2014Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Einarson, 2009Oberlander a, 2008Sivojelezova (Control unexposed, NOS), 2005Heikkinen, 2002

Asymetry test p-value = 0.1795 (by Egger's regression)

slope=0.1244 (0.0467); intercept=0.4935 (0.3442); t=1.4336; p=0.1795

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6415, 18283, 6391, 5884, 18165

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.18[1.09; 1.28]144,80618,7300%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, disease free), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 Heikkinen, 2002 12 unexposed, sick controlsunexposed, sick controls 1.18[0.94; 1.49]4442,77332%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 0.74[0.56; 0.97]2444,1110%NAChan (Controls exposed to TCA), 2024 Reis (Controls exposed to TCA), 2010 Sivojelezova (Control exposed to other SSRI), 2005 30.510.01.0