Citalopram 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.
S18165
R76396		 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
R76277		 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
R41459		 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
R21938		 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
R25493		 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
R22568		 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
R15380		 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
R14725		 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
R14740		 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
R61466		 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Major malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.99 [0.44;2.25]
excluded (control group) 		6/243   1,550/61,648 1,556 243
ref
S7834
R61480		 Nordeng - Citalopram/Escitalopram (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) 0.86 [0.35;2.09] C 6/243   30/1,048 36 243
ref
S7179
R20205		 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, ...) 1.25 [0.91;1.73] 39/775   3,834/94,561 3,873 775
ref
S18283
R76941		 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
R76945		 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
R15338		 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
R17640		 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
R17608		 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
R17600		 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
Total 12 studies 1.18 [1.09;1.27] 132,403 19,304
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]71,82011,19354%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 0.86[0.35; 2.09]362431%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.25[0.91; 1.73]3,8737755%ROB confusion: criticalROB selection: moderateROB classification: criticalROB 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 Total (12 studies) I2 = 0% 1.18[1.09; 1.27]132,40319,3040.250.01.0ROB: 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 1.18[1.09; 1.27]101,77319,1390%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 11 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) 1.18[1.08; 1.28]132,36716,5310%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 9 unexposed, sickunexposed, sick 1.14[0.86; 1.50]362,77342%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 1.25[1.00; 1.55]37,9501,5780%NAAnderson, 2020 Ozturk, 2016 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Colvin, 2011 Einarson, 2009 Oberlander a, 2008 Sivojelezova (Control unexposed, NOS), 2005 7   - 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 1.09[0.07; 17.70]2108 -NASivojelezova (Control unexposed, NOS), 2005 1 Monotherapy   - no or not specified  - no or not specified 1.38[0.65; 2.94]7453724%NAOzturk, 2016 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 Sivojelezova (Control unexposed, NOS), 2005 4   - 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, ...) 1.08[0.94; 1.24]7,2466,7720%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) 1.14[0.86; 1.50]362,77342%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 3 All studiesAll studies 1.18[1.09; 1.27]132,40319,3040%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 120.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.04.22.0630.000Chan (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), 2005

Asymetry test p-value = 0.3024 (by Egger's regression)

slope=0.1228 (0.0511); intercept=0.4212 (0.3874); t=1.0873; p=0.3024

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) 1.17[1.08; 1.26]142,76918,7200%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 11 unexposed, sick controlsunexposed, sick controls 1.14[0.86; 1.50]4072,77342%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

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Myles (Major congenital malformation)Myles (Major congenital malformation) 1.04[0.92; 1.17]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT7 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.17[0.84; 1.62]66%-U,Sunexposed, sickT11st trimesterstudies TTT2 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.19[1.09; 1.31]13.4%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT8 Kang (Major malformations)Kang (Major malformations) 1.07[0.98; 1.17]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT8 metaPregmetaPreg 1.18[1.09; 1.27]0%19,304----Chan (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 120.510.01.0