Tricyclic antidepressants updated on 07-01-2025

Neonatal medical care

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
R78344		 Lee (Controls exposed to SSRI), 2025 Admission to neonatal intensive care unit (NICU) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.23 [0.72;2.10] C
excluded (control group) 		21/613   41/1,465 62 613
ref
S18410
R77745		 Lee (Controls unexposed, general pop), 2025 Admission to neonatal intensive care unit (NICU) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: TCA only 1.10 [0.70;1.71] 21/613   8,566/463,440 8,587 613
ref
S10933
R41685		 Reis (Controls exposed to SSRIs), 2010 Respiratory diagnoses 2nd and/or 3rd trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.61 [1.25;2.08] C
excluded (control group) 		83/784   329/4,809 412 784
ref
S10934
R41679		 Reis (Controls unexposed, NOS), 2010 Respiratory diagnoses 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: TCA only 2.50 [1.99;3.14] 83/784   57,487/1,062,190 57,570 784
ref
S10930
R40633		 Davis, 2007 Respiratory distress syndrome and other respiratory conditions 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.02 [1.33;3.06] 19/136   5,393/75,957 5,412 136
ref
S11218
R41283		 Pearson (Controls exposed to SSRIs), 2007 Admission in Special care nursery of neonatal intensive care unit during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 3.13 [0.97;10.09] C
excluded (control group) 		11/37   5/42 16 37
ref
S11217
R41280		 Pearson (Controls unexposed, NOS), 2007 Admission in Special care nursery of neonatal intensive care unit during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: TCA only 3.76 [1.58;8.93] C 11/37   17/168 28 37
ref
Total 4 studies 2.03 [1.32;3.11] 71,597 1,570
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 1.10[0.70; 1.71]8,58761326%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 2 2.50[1.99; 3.14]57,57078433%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 2.02[1.33; 3.06]5,41213627%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Pearson (Controls unexposed, NOS), 2007Pearson, 2007 3 3.76[1.58; 8.93]283715%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 75% 2.03[1.32; 3.11]71,5971,5700.510.01.0ROB: 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; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.03[1.32; 3.11]71,5971,57075%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Pearson (Controls unexposed, NOS), 2007 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.03[1.32; 3.11]71,5971,57075%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Pearson (Controls unexposed, NOS), 2007 4 Tags Adjustment   - No  - No 2.44[1.39; 4.28]5,44017338%NADavis, 2007 Pearson (Controls unexposed, NOS), 2007 2   - Yes  - Yes 1.70[0.76; 3.79]66,1571,39790%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 2 Monotherapy   - no or not specified  - no or not specified 2.02[1.33; 3.06]5,412136 -NADavis, 2007 1   - TCA only  - TCA only 2.06[1.08; 3.94]66,1851,43483%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Pearson (Controls unexposed, NOS), 2007 3 All studiesAll studies 2.03[1.32; 3.11]71,5971,57075%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Pearson (Controls unexposed, NOS), 2007 40.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.61.70.5300.000Lee (Controls unexposed, general pop), 2025Reis (Controls unexposed, NOS), 2010Davis, 2007Pearson (Controls unexposed, NOS), 2007

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 11218, 10933, 18445

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.03[1.32; 3.11]71,5971,57075%NALee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Pearson (Controls unexposed, NOS), 2007 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.57[1.22; 2.03]4901,4348%NALee (Controls exposed to SSRI), 2025 Reis (Controls exposed to SSRIs), 2010 Pearson (Controls exposed to SSRIs), 2007 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 McDonagh (Respiratory distress)McDonagh (Respiratory distress) 2.11[1.57; 2.83]NA-U,GPunexposed (general population or NOS)Latelate pregnancystudies TTT2 metaPregmetaPreg 2.03[1.32; 3.11]75%1,570----Lee (Controls unexposed, general pop), 2025 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Pearson (Controls unexposed, NOS), 2007 40.510.01.0