Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) updated on 07-01-2025

Nervous system anomalies

id	Study   Auto Chan (Controls unexposed, sick), 2024Chan - SNRI (Controls exposed to TCA), 2024Chan - SNRI (Controls unexposed, general pop), 2024Benevent - SNRI, 2023Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine (Controls unexposed, sick), 2020Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S18317 R77148	Chan (Controls unexposed, sick), 2024	Nervous system malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	0.92 [0.06;15.07] C	0/66   36/4,413	36	66		ref
S18315 R77124	Chan - SNRI (Controls exposed to TCA), 2024	Nervous system malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	0.59 [0.03;11.64] C excluded (control group)	0/77   3/322	3	77		ref
S18316 R77136	Chan - SNRI (Controls unexposed, general pop), 2024	Nervous system malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: No Monotherapy: SNRI only	1.58 [0.10;25.57] C excluded (control group)	0/77   1,899/462,377	1,899	77		ref
S15171 R62279	Benevent - SNRI, 2023	Nervous system anomalies	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	1.79 [0.25;12.83] C	1/314   261/146,855	262	314		ref
S11684 R42948	Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021	Nervous system malformations	1st trimester	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.00 [0.28;3.54] excluded (control group)	-/1,438   12/5,751	-	1,438		ref
S11685 R42964	Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021	Nervous system malformations	1st trimester	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.50 [0.25;8.98]	-/1,434   -/1,435	-	1,434		ref
S11745 R43129	Huybrechts - Duloxetine (Controls unexposed, NOS), 2020	Central Nervous System malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	0.81 [0.30;2.16] excluded (control group)	-/2,532   -/-	-	2,532		ref
S11746 R43143	Huybrechts - Duloxetine (Controls unexposed, sick), 2020	Central Nervous System malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.67 [0.18;2.42]	-/2,532   -/2,456	-	2,532		ref
S11696 R43024	Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	Nervous system malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.19 [0.55;2.58]	-/738   -/14,847	-	738		ref
					Total	5 studies	1.11 [0.62;1.99]		298	5,084
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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 11745, 11684, 18315, 18316

Umbrella review (other published meta-analyses)