Tricyclic antidepressants updated on 07-01-2025

Cognitive developmental disorders/delay (3-6 years old)

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.
S18247
R76895		 Suarez (Controls unexposed, discontinuers), 2022 Intellectual disability - ≥ 2 dates with ICD-9 Dx 317, 318.x, 319 - At ≥ 2 years of age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.95 [0.29;3.16] -/3,494   -/4,258 - 3,494
ref
S18248
R76896		 Suarez (Controls unexposed, general pop), 2022 Intellectual disability - ≥ 2 dates with ICD-9 Dx 317, 318.x, 319 - At ≥ 2 years of age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.52 [0.21;1.27]
excluded (control group) 		-/3,511   2,852/1,789,773 - 3,511
ref
S10954
R53836		 Nulman (Controls unexposed, disease free), 2002 Global IQ with the McCarthy Scales of Children’s Abilities at 30 and 71 months of age throughout pregnancy prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only 1.11 [0.33;3.78] -/18   -/16 - 18
ref
S10953
R53837		 Nulman - Fluoxetine (Controls exposed to Fluoxetine), 2002 Global IQ with the McCarthy Scales of Children’s Abilities at 30 and 71 months of age throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only 0.30 [0.05;1.66]
excluded (control group) 		-/18   -/6 - 18
ref
Total 2 studies 1.03 [0.44;2.41] 0 3,512
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 Suarez (Controls unexposed, discontinuers), 2022Suarez, 2022 1 0.95[0.29; 3.16]-3,49451%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Nulman (Controls unexposed, disease free), 2002Nulman, 2002 2 1.11[0.33; 3.78]-1849%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: lowROB reporting: moderate Total (2 studies) I2 = 0% 1.03[0.44; 2.41]-3,5120.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, discontinuers; 2: Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.03[0.44; 2.41]-3,5120%NASuarez (Controls unexposed, discontinuers), 2022 Nulman (Controls unexposed, disease free), 2002 2 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.11[0.33; 3.76]-18 -NANulman (Controls unexposed, disease free), 2002 1 unexposed, sickunexposed, sick 0.95[0.29; 3.14]-3,494 -NASuarez (Controls unexposed, discontinuers), 2022 1 Tags Adjustment   - No  - No 1.11[0.33; 3.76]-18 -NANulman (Controls unexposed, disease free), 2002 1   - Yes  - Yes 0.95[0.29; 3.14]-3,494 -NASuarez (Controls unexposed, discontinuers), 2022 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.11[0.33; 3.76]-18 -NANulman (Controls unexposed, disease free), 2002 1 Monotherapy   - no or not specified  - no or not specified 0.95[0.29; 3.14]-3,494 -NASuarez (Controls unexposed, discontinuers), 2022 1   - TCA only  - TCA only 1.11[0.33; 3.76]-18 -NANulman (Controls unexposed, disease free), 2002 1 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.95[0.29; 3.14]-3,494 -NASuarez (Controls unexposed, discontinuers), 2022 1 All studiesAll studies 1.03[0.44; 2.41]-3,5120%NASuarez (Controls unexposed, discontinuers), 2022 Nulman (Controls unexposed, disease free), 2002 20.25.01.0

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 10953, 18248

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.68[0.33; 1.40]2,8433,5290%NASuarez (Controls unexposed, general pop), 2022 Nulman (Controls unexposed, disease free), 2002 2 unexposed, sick controlsunexposed, sick controls 0.95[0.29; 3.14]-3,494 -NASuarez (Controls unexposed, discontinuers), 2022 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.30[0.05; 1.73]-18 -NANulman - Fluoxetine (Controls exposed to Fluoxetine), 2002 10.510.01.0