Tricyclic antidepressants updated on 07-01-2025

Small for gestational age (weight)

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.
S18445
R78339
Lee (Controls exposed to SSRI), 2025 Small for gestational age (birth weight <2 standard deviations below the mean for gestational age) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.20 [0.64;2.25] C
excluded (control group)
15/613   30/1,465 45 613
ref
S18410
R77740
Lee (Controls unexposed, general pop), 2025 Small for gestational age (birth weight <2 standard deviations below the mean for gestational age) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: TCA only 1.07 [0.63;1.81] 15/613   6,986/463,440 7,001 613
ref
S18222
R76451
Martin - Amitriptyline, 2024 Small for gestational age (SGA, defined as those with a birth weight in the lowest 10 percentiles for gestational age (<10th percentile) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.00 [0.90;1.11] 433/3,859   229,066/2,408,707 229,499 3,859
ref
S10933
R41672
Reis (Controls exposed to SSRIs), 2010 Small for gestational age (<2 S.D. from expected weight) 2nd and/or 3rd trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.70 [0.40;1.22] C
excluded (control group)
14/784   122/4,809 136 784
ref
S10934
R41665
Reis (Controls unexposed, NOS), 2010 Small for gestational age (<2 S.D. from expected weight) 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: TCA only 0.77 [0.45;1.32] 14/784   24,802/1,062,190 24,816 784
ref
Total 3 studies 0.99 [0.90;1.10] 261,316 5,256
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 Lee (Controls unexposed, general pop), 2025Lee, 2025 1 1.07[0.63; 1.81]7,0016134%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Martin - Amitriptyline, 2024Martin - Amitriptyline, 2024 1.00[0.90; 1.11]229,4993,85993%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 2 0.77[0.45; 1.32]24,8167844%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 0.99[0.90; 1.10]261,3165,2560.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.99[0.90; 1.10]261,3165,2560%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.99[0.90; 1.10]261,3165,2560%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 3 Tags Adjustment   - Yes  - Yes 0.99[0.90; 1.10]261,3165,2560%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 3 Monotherapy   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.00[0.90; 1.11]229,4993,859 -NAMartin - Amitriptyline, 2024 1   - TCA only  - TCA only 0.91[0.62; 1.33]31,8171,3970%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 2 All studiesAll studies 0.99[0.90; 1.10]261,3165,2560%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 30.25.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 10933, 18445

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.99[0.90; 1.10]261,3165,2560%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.90[0.53; 1.52]1811,39737%NALee (Controls exposed to SSRI), 2025 Reis (Controls exposed to SSRIs), 2010 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Vlenterie (Small for gestational age)Vlenterie (Small for gestational age) Out of scale0.40[0.10; 1.30]-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT2 Vlenterie (Small for gestational age)Vlenterie (Small for gestational age) 1.50[0.50; 4.40]-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Xing (Small for gestational age)Xing (Small for gestational age) 0.94[0.78; 1.13]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 0.99[0.90; 1.10]0%5,256----Lee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Reis (Controls unexposed, NOS), 2010 30.510.01.0