Tricyclic antidepressants updated on 07-01-2025

Nervous system anomalies

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
R76381		 Chan (Controls exposed to SSRIs), 2024 Nervous system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.11 [0.29;4.23] C
excluded (control group) 		3/322   8/956 11 322
ref
S18156
R76335		 Chan (Controls unexposed, general pop), 2024 Nervous system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: TCA only 1.95 [0.59;6.47]
excluded (control group) 		3/322   1,899/462,377 1,902 322
ref
S18157
R76346		 Chan (Controls unexposed, sick), 2024 Nervous system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: TCA only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 0.68 [0.09;4.95] C 1/181   36/4,413 37 181
ref
S11052
R40979		 Bérard (Controls unexposed, sick), 2017 Nervous 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) 0.60 [0.15;2.38] -/382   -/14,847 - 382
ref
S10937
R40709		 Ban (Controls exposed to SSRIs), 2014 Nervous system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.48 [0.60;3.63] C
excluded (control group) 		7/2,428   15/7,683 22 2,428
ref
S10938
R40725		 Ban (Controls unexposed, disease free), 2014 Nervous system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: TCA only 1.86 [0.88;3.92]
excluded (control group) 		7/2,428   465/325,294 472 2,428
ref
S10939
R40747		 Ban (Controls unexposed, sick), 2014 Nervous 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) 1.62 [0.70;3.75] C 7/2,428   24/13,432 31 2,428
ref
S10943
R40769		 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 Central nervous system 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
R40777		 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Central nervous system anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Matched Monotherapy: TCA only 4.20 [0.60;29.50] 2/1,608   2/6,617 4 1,608
ref
Total 4 studies 1.31 [0.66;2.61] 72 4,599
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 0.68[0.09; 4.95]3718111%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bérard (Controls unexposed, sick), 2017Bérard, 2017 2 0.60[0.15; 2.38]-38223%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 3 1.62[0.70; 3.75]312,42854%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Vasilakis-Scaramozza, 2013 4 4.20[0.60; 29.50]41,60812%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 8% 1.31[0.66; 2.61]724,5990.210.01.0ROB: 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 1.31[0.66; 2.61]724,5998%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 4.20[0.60; 29.45]41,608 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 unexposed, sickunexposed, sick 1.15[0.59; 2.27]682,9910%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 1.64[0.80; 3.38]724,2170%NAChan (Controls unexposed, sick), 2024 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 3   - Yes  - Yes 0.60[0.15; 2.39]-382 -NABérard (Controls unexposed, sick), 2017 1 MatchedMatched 4.20[0.60; 29.45]41,608 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 Monotherapy   - TCA only  - TCA only 1.31[0.66; 2.61]724,5998%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) 1.15[0.46; 2.89]312,81030%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 0.68[0.09; 4.95]37181 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.31[0.66; 2.61]724,5998%NAChan (Controls unexposed, sick), 2024 Bérard (Controls unexposed, sick), 2017 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.71.2200.000Chan (Controls unexposed, sick), 2024Bérard (Controls unexposed, sick), 2017Ban (Controls unexposed, sick), 2014Vasilakis-Scaramozza (Controls unexposed, NOS), 2013

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

not enought points

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) 2.04[1.11; 3.72]2,3784,3580%NAChan (Controls unexposed, general pop), 2024 Ban (Controls unexposed, disease free), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 3 unexposed, sick controlsunexposed, sick controls 1.15[0.59; 2.27]682,9910%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 1.32[0.66; 2.66]374,3580%NAChan (Controls exposed to SSRIs), 2024 Ban (Controls exposed to SSRIs), 2014 Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013 30.510.01.0