Tricyclic antidepressants updated on 07-01-2025

Urinary 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.
S18161
R76383		 Chan (Controls exposed to SSRIs), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.45 [0.10;2.02] C
excluded (control group) 		2/322   13/956 15 322
ref
S18156
R76337		 Chan (Controls unexposed, general pop), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: TCA only 2.33 [0.54;9.94]
excluded (control group) 		2/322   3,740/462,377 3,742 322
ref
S18157
R76348		 Chan (Controls unexposed, sick), 2024 Urinary system 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 1.09 [0.13;8.90] 1/181   51/4,413 52 181
ref
S11052
R40985		 Bérard (Controls unexposed, sick), 2017 Urinary system 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) 0.80 [0.25;2.57] -/382   -/14,847 - 382
ref
S10937
R40706		 Ban (Controls exposed to SSRIs), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.24 [0.57;2.68] C
excluded (control group) 		9/2,428   23/7,683 32 2,428
ref
S10938
R40722		 Ban (Controls unexposed, disease free), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: TCA only 1.46 [0.76;2.83]
excluded (control group) 		9/2,428   815/325,294 824 2,428
ref
S10939
R40744		 Ban (Controls unexposed, sick), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: TCA only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.35 [0.65;2.79] C 9/2,428   37/13,432 46 2,428
ref
S10943
R40773		 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 Urinary anomalies 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.14 [0.16;8.07] C
excluded (control group) 		2/1,608   2/1,825 4 1,608
ref
S10944
R40781		 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Urinary anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: TCA only 1.30 [0.30;6.10] 2/1,608   5/6,617 7 1,608
ref
S10930
R40608		 Davis, 2007 Congenital anomalies of urinary system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.64 [0.09;4.53] 1/167   469/49,669 470 167
ref
Total 5 studies 1.12 [0.66;1.91] 575 4,766
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 1.09[0.13; 8.90]521816%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bérard (Controls unexposed, sick), 2017Bérard, 2017 2 0.80[0.25; 2.57]-38221%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 3 1.35[0.65; 2.79]462,42853%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Vasilakis-Scaramozza, 2013 4 1.30[0.30; 6.10]71,60812%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 0.64[0.09; 4.53]4701677%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.12[0.66; 1.91]5754,7660.25.01.0ROB: 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, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.12[0.66; 1.91]5754,7660%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.00[0.30; 3.30]4771,7750%NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 2 unexposed, sickunexposed, sick 1.16[0.64; 2.09]982,9910%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 1.23[0.62; 2.44]5162,5950%NABan (Controls unexposed, sick), 2014 Davis, 2007 2   - Yes  - Yes 0.98[0.42; 2.28]592,1710%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 3 MatchedMatched 1.30[0.29; 5.86]71,608 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 Monotherapy   - no or not specified  - no or not specified 0.64[0.09; 4.54]470167 -NADavis, 2007 1   - TCA only  - TCA only 1.18[0.68; 2.04]1054,5990%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) 1.16[0.63; 2.16]462,8100%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 1.09[0.13; 9.02]52181 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.12[0.66; 1.91]5754,7660%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.52.71.2940.000Chan (Controls unexposed, sick), 2024Bérard (Controls unexposed, sick), 2017Ban (Controls unexposed, sick), 2014Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Davis, 2007

Asymetry test p-value = 0.2986 (by Egger's regression)

slope=0.4779 (0.3125); intercept=-0.6463 (0.5154); t=1.2541; p=0.2986

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10943, 10937, 10938, 18161, 18156

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.44[0.84; 2.46]5,0434,5250%NAChan (Controls unexposed, general pop), 2024 Ban (Controls unexposed, disease free), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Davis, 2007 4 unexposed, sick controlsunexposed, sick controls 1.16[0.64; 2.09]982,9910%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.02[0.53; 1.94]514,3580%NAChan (Controls exposed to SSRIs), 2024 Ban (Controls exposed to SSRIs), 2014 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 30.510.01.0