Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) 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.
S18333
R77347		 Suarez - SNRI (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) 1.21 [0.47;3.10] -/5,090   11/3,245 - 5,090
ref
S18334
R77358		 Suarez - SNRI (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 0.80 [0.41;1.56]
excluded (control group) 		-/5,148   2,748/1,730,176 - 5,148
ref
S11778
R53842		 Nulman - Venlafaxine (Controls unexposed, disease free), 2012 Full-scale IQ (The Wechsler Preschool and Primary Scale of Intelligence– Third Edition) at 3-6 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No extrapolated (cont. endpoint) Monotherapy: SNRI only 2.72 [1.42;5.22]
excluded (control group) 		-/62   -/62 - 62
ref
S11779
R53843		 Nulman - Venlafaxine (Controls unexposed, sick), 2012 Full-scale IQ (The Wechsler Preschool and Primary Scale of Intelligence– Third Edition) at 3-6 years during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.47 [0.76;2.86] -/62   -/54 - 62
ref
Total 2 studies 1.38 [0.80;2.37] 0 5,152
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 - SNRI (Controls unexposed, discontinuers), 2022Suarez - SNRI, 2022 1 1.21[0.47; 3.10]-5,09033%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Nulman - Venlafaxine (Controls unexposed, sick), 2012Nulman - Venlafaxine, 2012 2 1.47[0.76; 2.86]-6267%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Total (2 studies) I2 = 0% 1.38[0.80; 2.37]-5,1520.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, discontinuers; 2: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.38[0.80; 2.37]-5,1520%NASuarez - SNRI (Controls unexposed, discontinuers), 2022 Nulman - Venlafaxine (Controls unexposed, sick), 2012 2 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.38[0.80; 2.37]-5,1520%NASuarez - SNRI (Controls unexposed, discontinuers), 2022 Nulman - Venlafaxine (Controls unexposed, sick), 2012 2 Tags Adjustment   - No  - No 1.47[0.76; 2.85]-62 -NANulman - Venlafaxine (Controls unexposed, sick), 2012 1   - Yes  - Yes 1.21[0.47; 3.11]-5,090 -NASuarez - SNRI (Controls unexposed, discontinuers), 2022 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.47[0.76; 2.85]-62 -NANulman - Venlafaxine (Controls unexposed, sick), 2012 1 Monotherapy   - no or not specified  - no or not specified 1.21[0.47; 3.11]-5,090 -NASuarez - SNRI (Controls unexposed, discontinuers), 2022 1   - SNRI only  - SNRI only 1.47[0.76; 2.85]-62 -NANulman - Venlafaxine (Controls unexposed, sick), 2012 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.47[0.76; 2.85]-62 -NANulman - Venlafaxine (Controls unexposed, sick), 2012 1   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.21[0.47; 3.11]-5,090 -NASuarez - SNRI (Controls unexposed, discontinuers), 2022 1 All studiesAll studies 1.38[0.80; 2.37]-5,1520%NASuarez - SNRI (Controls unexposed, discontinuers), 2022 Nulman - Venlafaxine (Controls unexposed, sick), 2012 20.55.01.0

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 11778, 18334

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.48[0.45; 4.91]2,7395,21085%NASuarez - SNRI (Controls unexposed, general pop), 2022 Nulman - Venlafaxine (Controls unexposed, disease free), 2012 2 unexposed, sick controlsunexposed, sick controls 1.38[0.80; 2.37]25,1520%NASuarez - SNRI (Controls unexposed, discontinuers), 2022 Nulman - Venlafaxine (Controls unexposed, sick), 2012 20.510.01.0