Escitalopram 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.
S18166
R76398
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, ...) 0.53 [0.12;2.31] C
excluded (control group)
2/47   25/322 27 47
ref
S18145
R76283
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, ...) 0.74 [0.18;3.07] 2/47   22,628/462,377 22,630 47
ref
S7472
R41461
Anderson, 2020 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.09 [0.74;1.60] C 102/137   30,528/41,971 30,630 137
ref
S8218
R25661
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 1.01 [0.81;1.25]
excluded (exposition period)
86/3,236   13,536/506,155 13,622 3,236
ref
S7520
R22540
Ozturk, 2016 Major congenital defects at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.17 [0.06;23.30] C 0/30   3/246 3 30
ref
S6009
R15435
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, ...) 0.89 [0.73;1.10] 107/3,950   71,374/2,266,875 71,481 3,950
ref
S5890
R14782
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, ...) 0.85 [0.40;1.81]
excluded (control group)
-/933   8,731/325,294 - 933
ref
S5891
R14797
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) 0.77 [0.36;1.66] -/933   380/13,432 - 933
ref
S6190
R16310
Klieger-Grossmann, 2012 Major malformation (among live births) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.68 [0.28;10.16] C 3/172   2/191 5 172
ref
S15006
R61469
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
S15007
R61483
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
S5967
R15343
Einarson, 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.86 [0.05;14.67] C 0/21   25/928 25 21
ref
Total 8 studies 0.92 [0.78;1.09] 124,810 5,533
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 0.74[0.18; 3.07]22,630471%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.09[0.74; 1.60]30,63013720%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Ozturk, 2016Ozturk, 2016 1.17[0.06; 23.30]3300%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 0.89[0.73; 1.10]71,4813,95069%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 0.77[0.36; 1.66]-9335%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Klieger-Grossmann, 2012Klieger-Grossmann, 2012 1.68[0.28; 10.16]51721%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Nordeng - Citalopram/Escitalo..., 2012 3 0.86[0.35; 2.09]362434%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Einarson, 2009Einarson, 2009 0.86[0.05; 14.67]25210%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (8 studies) I2 = 0% 0.92[0.78; 1.09]124,8105,5330.25.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.88[0.73; 1.07]94,1805,3960%NAChan (Controls unexposed, pop general), 2024 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Klieger-Grossmann, 2012 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 7 case control studiescase control studies 1.09[0.74; 1.60]30,630137 -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.93[0.78; 1.12]124,7744,3570%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Klieger-Grossmann, 2012 Einarson, 2009 6 unexposed, sickunexposed, sick 0.81[0.45; 1.44]361,1760%NABan (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 2 Tags Adjustment   - No  - No 1.07[0.76; 1.50]30,6996030%NAAnderson, 2020 Ozturk, 2016 Klieger-Grossmann, 2012 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 5   - Yes  - Yes 0.88[0.72; 1.07]94,1114,9300%NAChan (Controls unexposed, pop general), 2024 Furu, 2015 Ban (Controls unexposed, sick), 2014 3 MatchedMatched 1.68[0.28; 10.16]5172 -NAKlieger-Grossmann, 2012 1 Monotherapy   - no or not specified  - no or not specified 0.88[0.39; 1.99]642940%NAOzturk, 2016 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 3   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.93[0.78; 1.12]124,7464,3060%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Klieger-Grossmann, 2012 4   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.77[0.36; 1.65]-933 -NABan (Controls unexposed, sick), 2014 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.81[0.45; 1.44]361,1760%NABan (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 2 All studiesAll studies 0.92[0.78; 1.09]124,8105,5330%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, sick), 2014 Klieger-Grossmann, 2012 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 Einarson, 2009 80.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.51.8290.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Ozturk, 2016Furu, 2015Ban (Controls unexposed, sick), 2014Klieger-Grossmann, 2012Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012Einarson, 2009

Asymetry test p-value = 0.7326 (by Egger's regression)

slope=-0.0975 (0.0641); intercept=0.0935 (0.2611); t=0.3581; p=0.7326

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 15006, 5890, 18166

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.93[0.79; 1.10]135,0525,5330%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk, 2016 Furu, 2015 Ban (Controls unexposed, disease free), 2014 Klieger-Grossmann, 2012 Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012 Einarson, 2009 8 unexposed, sick controlsunexposed, sick controls 0.81[0.45; 1.44]4071,1760%NABan (Controls unexposed, sick), 2014 Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.53[0.12; 2.31]2747 -NAChan (Controls exposed to TCA), 2024 10.510.01.0