Tricyclic antidepressants updated on 07-01-2025

Psychomotor developmental disorders/delay

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
R76564		 Suarez (Controls unexposed, discontinuers), 2022 Developmental Coordination Disorder - ≥ 2 dates with ICD-9 Dx 315.4 - At any 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) 0.76 [0.36;1.60] 19/4,307   26/5,710 45 4,307
ref
S18248
R76572		 Suarez (Controls unexposed, general pop), 2022 Developmental Coordination Disorder - ≥ 2 dates with ICD-9 Dx 315.4 - At any age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.91 [0.58;1.45]
excluded (control group) 		19/4,357   10,397/2,965,988 10,416 4,357
ref
S11279
R41429		 Pedersen, 2010 Unable to sit without Support at 6 months (interviews with the mothers) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: TCA only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 2.90 [0.89;9.51] -/-   258/362 - -
ref
S10954
R40804		 Nulman (Controls unexposed, disease free), 2002 Psychomotor development IQ with Bayley Scales of Infant Development-II at 15 and 30 months of age throughout pregnancy prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only 0.76 [0.26;2.22] -/28   -/18 - 28
ref
S10953
R40799		 Nulman - Fluoxetine (Controls exposed to Fluoxetine), 2002 Psychomotor development IQ with Bayley Scales of Infant Development-II at 15 and 30 months of age throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only 0.69 [0.28;1.73]
excluded (control group) 		-/28   -/33 - 28
ref
S10935
R40682		 Simon (Controls exposed to SSRIs), 2002 Motor delay (infants’ medical records) - unspecified age during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 0.29 [0.06;1.45] C
excluded (control group) 		2/209   6/185 8 209
ref
S10936
R40698		 Simon (Controls unexposed, NOS), 2002 Motor delay (infants’ medical records) - unspecified age during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: TCA only 1.00 [0.14;7.17] 2/209   2/209 4 209
ref
Total 4 studies 1.05 [0.56;1.97] 49 4,544
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 0.76[0.36; 1.60]454,30743%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Pedersen, 2010Pedersen, 2010 2.90[0.89; 9.51]--22%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Nulman (Controls unexposed, disease free), 2002Nulman, 2002 2 0.76[0.26; 2.22]-2826%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: lowROB reporting: moderate Simon (Controls unexposed, NOS), 2002Simon, 2002 3 1.00[0.14; 7.17]42099%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (4 studies) I2 = 23% 1.05[0.56; 1.97]494,5440.210.01.0ROB: 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; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.05[0.56; 1.97]494,54423%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 Nulman (Controls unexposed, disease free), 2002 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) 0.81[0.32; 2.08]42370%NANulman (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 2 unexposed, sickunexposed, sick 1.37[0.37; 5.03]454,30772%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 2 Tags Adjustment   - No  - No 0.76[0.26; 2.22]-28 -NANulman (Controls unexposed, disease free), 2002 1   - Yes  - Yes 1.24[0.50; 3.08]494,51643%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 Simon (Controls unexposed, NOS), 2002 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 0.76[0.26; 2.22]-28 -NANulman (Controls unexposed, disease free), 2002 1 MatchedMatched 1.00[0.14; 7.16]4209 -NASimon (Controls unexposed, NOS), 2002 1 Monotherapy   - no or not specified  - no or not specified 0.76[0.36; 1.60]454,307 -NASuarez (Controls unexposed, discontinuers), 2022 1   - TCA only  - TCA only 1.34[0.54; 3.29]423728%NAPedersen, 2010 Nulman (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 3 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.37[0.37; 5.03]454,30772%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 2 All studiesAll studies 1.05[0.56; 1.97]494,54423%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 Nulman (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.41.2050.000Suarez (Controls unexposed, discontinuers), 2022Pedersen, 2010Nulman (Controls unexposed, disease free), 2002Simon (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 10953, 10935, 18248

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.89[0.59; 1.34]10,4204,5940%NASuarez (Controls unexposed, general pop), 2022 Nulman (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 3 unexposed, sick controlsunexposed, sick controls 1.37[0.37; 5.03]2944,30772%NASuarez (Controls unexposed, discontinuers), 2022 Pedersen, 2010 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.56[0.25; 1.23]82370%NANulman - Fluoxetine (Controls exposed to Fluoxetine), 2002 Simon (Controls exposed to SSRIs), 2002 20.510.01.0