Tricyclic antidepressants 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.
S18161
R76380		 Chan (Controls exposed to SSRIs), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.37 [0.67;2.84] C
excluded (control group) 		11/322   24/956 35 322
ref
S18156
R76334		 Chan (Controls unexposed, general pop), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: TCA only 1.71 [0.89;3.28]
excluded (control group) 		11/322   8,107/462,377 8,118 322
ref
S18157
R76345		 Chan (Controls unexposed, sick), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: TCA only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 0.98 [0.27;3.51] 3/181   95/4,413 98 181
ref
S11052
R40987		 Bérard (Controls unexposed, sick), 2017 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: TCA only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.05 [0.55;1.99] -/382   -/14,847 - 382
ref
S10937
R40703		 Ban (Controls exposed to SSRIs), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.93 [0.56;1.53] C
excluded (control group) 		20/2,428   68/7,683 88 2,428
ref
S10938
R40719		 Ban (Controls unexposed, disease free), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: TCA only 1.03 [0.65;1.63]
excluded (control group) 		20/2,428   2,444/325,294 2,464 2,428
ref
S10939
R40741		 Ban (Controls unexposed, sick), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: TCA only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.90 [0.54;1.50] 20/2,428   112/13,432 132 2,428
ref
S10941
R40760		 Huybrechts (Controls unexposed, NOS), 2014 Any cardiac malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 0.98 [0.72;1.32]
excluded (control group) 		42/5,954   6,403/885,115 6,445 5,954
ref
S10942
R40764		 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 0.72 [0.48;1.08] 27/3,287   1,497/180,547 1,524 3,287
ref
S11668
R42772		 Källen, 2013 Any cardiac defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.29 [0.93;1.79] 36/2,139   -/- - 2,139
ref
S10943
R40771		 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 Cardiovascular anomalies 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.79 [0.69;4.63] C
excluded (control group) 		11/1,608   7/1,825 18 1,608
ref
S10944
R40779		 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Cardiovascular anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Matched Monotherapy: TCA only 1.60 [0.80;3.10] 11/1,608   28/6,617 39 1,608
ref
S10930
R41658		 Davis, 2007 Congenital anomalies of heart 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.50 [0.12;2.00] C 2/167   1,186/49,669 1,188 167
ref
S10935
R40677		 Simon (Controls exposed to SSRIs), 2002 Cardiac malformations during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.22 [0.02;1.96] C
excluded (control group) 		1/209   4/185 5 209
ref
S10936
R40693		 Simon (Controls unexposed, NOS), 2002 Cardiac malformations during pregnancy (anytime or not specified) excluded retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Matched Monotherapy: TCA only 0.50 [0.05;5.53]
excluded (exposition period) 		1/209   2/209 3 209
ref
Total 7 studies 1.02 [0.80;1.30] 2,981 10,192
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, sick), 2024Chan, 2024 1 0.98[0.27; 3.51]981813%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bérard (Controls unexposed, sick), 2017Bérard, 2017 2 1.05[0.55; 1.99]-38212%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 3 0.90[0.54; 1.50]1322,42817%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Huybrechts (Controls unexposed, sick), 2014Huybrechts, 2014 4 0.72[0.48; 1.08]1,5243,28723%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källen, 2013Källen, 2013 1.29[0.93; 1.79]-2,13930%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Vasilakis-Scaramozza, 2013 5 1.60[0.80; 3.10]391,60811%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 0.50[0.12; 2.00]1,1881673%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 23% 1.02[0.80; 1.30]2,98110,1920.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 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 1.02[0.80; 1.30]2,98110,19223%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Källen, 2013 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.28[0.92; 1.79]1,2273,9149%NAKällen, 2013 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 3 unexposed, sickunexposed, sick 0.84[0.63; 1.11]1,7546,2780%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 4 Tags Adjustment   - No  - No 1.05[0.35; 3.16]1,2271,77554%NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 2   - Yes  - Yes 0.99[0.77; 1.27]1,7548,41720%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Källen, 2013 5 MatchedMatched 1.60[0.81; 3.15]391,608 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 Monotherapy   - no or not specified  - no or not specified 0.91[0.54; 1.52]2,7125,59366%NAHuybrechts (Controls unexposed, sick), 2014 Källen, 2013 Davis, 2007 3   - TCA only  - TCA only 1.08[0.78; 1.51]2694,5990%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.96[0.64; 1.43]1322,8100%NABérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 2   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 0.74[0.50; 1.09]1,6223,4680%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2014 2 All studiesAll studies 1.02[0.80; 1.30]2,98110,19223%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Källen, 2013 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.70.8540.000Chan (Controls unexposed, sick), 2024Bérard (Controls unexposed, sick), 2017Ban (Controls unexposed, sick), 2014Huybrechts (Controls unexposed, sick), 2014Källen, 2013Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Davis, 2007

Asymetry test p-value = 0.6365 (by Egger's regression)

slope=0.1653 (0.2968); intercept=-0.5522 (1.0986); t=0.5027; p=0.6365

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10935, 10943, 10937, 10938, 10941, 18161, 18156

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.16[0.95; 1.41]18,28112,6189%NAChan (Controls unexposed, general pop), 2024 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, NOS), 2014 Källen, 2013 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 6 unexposed, sick controlsunexposed, sick controls 0.84[0.63; 1.11]1,7546,2780%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.15[0.79; 1.67]1414,3580%NAChan (Controls exposed to SSRIs), 2024 Ban (Controls exposed to SSRIs), 2014 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Viswanathan (Cardiac anomalies)Viswanathan (Cardiac anomalies) 0.86[0.65; 1.13]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 McDonagh (Cardiac malformations)McDonagh (Cardiac malformations) 1.58[1.10; 2.29]NA-NAnot specifiedstudies TTT-9 De Vries (Congenital heart defects)De Vries (Congenital heart defects) 1.02[0.82; 1.25]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 1.02[0.80; 1.30]23%10,192----Chan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Källen, 2013 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 70.510.01.0