Tricyclic antidepressants updated on 07-01-2025

Low Apgar score (< 7) (at 5 min)

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
R78342
Lee (Controls exposed to SSRI), 2025 5-minute Apgar score<7 during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 2.40 [0.69;8.32] C
excluded (control group)
5/613   5/1,465 10 613
ref
S18410
R77743
Lee (Controls unexposed, general pop), 2025 5-minute Apgar score<7 during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: TCA only 1.61 [0.65;3.99] 5/613   1,721/463,440 1,726 613
ref
S18222
R76452
Martin - Amitriptyline, 2024 Low Apgar score at 5 min (<7) 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, ...) 0.94 [0.70;1.26] 51/2,899   30,996/2,078,011 31,047 2,899
ref
S11668
R42787
Källen, 2013 Apgar score at 5min <7 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.07 [1.23;3.27] 18/394   -/- - 394
ref
S10935
R40673
Simon (Controls exposed to SSRIs), 2002 Apgar score at 5 minutes ≤7 during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.41 [0.19;0.91] C
excluded (control group)
10/209   20/185 30 209
ref
S10936
R40689
Simon (Controls unexposed, NOS), 2002 Apgar score at 5 minutes ≤7 during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: TCA only 1.29 [0.47;2.22] 10/209   8/209 18 209
ref
Total 4 studies 1.36 [0.87;2.14] 32,791 4,115
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 1.61[0.65; 3.99]1,72661316%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Martin - Amitriptyline, 2024Martin - Amitriptyline, 2024 0.94[0.70; 1.26]31,0472,89937%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Källen, 2013Källen, 2013 2.07[1.23; 3.27]-39429%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Simon (Controls unexposed, NOS), 2002Simon, 2002 2 1.29[0.47; 2.22]1820919%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 62% 1.36[0.87; 2.14]32,7914,1150.25.01.0ROB: 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 1.36[0.87; 2.14]32,7914,11562%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.36[0.87; 2.14]32,7914,11562%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 4 Tags Adjustment   - Yes  - Yes 1.36[0.87; 2.14]32,7914,11562%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 4 MatchedMatched 1.29[0.59; 2.80]18209 -NASimon (Controls unexposed, NOS), 2002 1 Monotherapy   - no or not specified  - no or not specified 2.07[1.27; 3.38]-394 -NAKällen, 2013 1   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.94[0.70; 1.26]31,0472,899 -NAMartin - Amitriptyline, 2024 1   - TCA only  - TCA only 1.42[0.79; 2.56]1,7448220%NALee (Controls unexposed, general pop), 2025 Simon (Controls unexposed, NOS), 2002 2 All studiesAll studies 1.36[0.87; 2.14]32,7914,11562%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.11.40.5550.000Lee (Controls unexposed, general pop), 2025Martin - Amitriptyline, 2024Källen, 2013Simon (Controls unexposed, NOS), 2002

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 10935, 18445

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.36[0.87; 2.14]32,8004,11562%NALee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.93[0.17; 5.18]4082282%NALee (Controls exposed to SSRI), 2025 Simon (Controls exposed to SSRIs), 2002 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Vlenterie (Low 5-min Apgar score)Vlenterie (Low 5-min Apgar score) 1.20[0.10; 18.30]-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT4 Vlenterie (Low 5-min Apgar score)Vlenterie (Low 5-min Apgar score) 1.30[0.10; 17.70]-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 1.36[0.87; 2.14]62%4,115----Lee (Controls unexposed, general pop), 2025 Martin - Amitriptyline, 2024 Källen, 2013 Simon (Controls unexposed, NOS), 2002 40.510.01.0