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

Congenital heart defects

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), 2021Marks - Duloxetine (Controls exposed to Bupropion), 2021Anderson - SNRI, 2020Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine (Controls unexposed, sick), 2020Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017Furu - Venlafaxine, 2015Huybrechts - SNRI (Controls unexposed, NOS), 2014Huybrechts - SNRI (Controls unexposed, sick), 2014Reis - SNRI (Controls exposed to TCA), 2010Reis - SNRI (Controls unexposed, NOS), 2010Oberlander - Venlafaxine, 2008	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 R77147	Chan (Controls unexposed, sick), 2024	Cardiac malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: SNRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	2.90 [1.03;8.16]	4/66   95/4,413	99	66		ref
S18315 R77123	Chan - SNRI (Controls exposed to TCA), 2024	Cardiac malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	1.96 [0.66;5.83] C excluded (control group)	5/77   11/322	16	77		ref
S18316 R77135	Chan - SNRI (Controls unexposed, general pop), 2024	Cardiac malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: SNRI only	3.73 [0.94;14.84] excluded (control group)	5/77   8,107/462,377	8,112	77		ref
S15171 R62282	Benevent - SNRI, 2023	Circulatory system anomaly	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	0.36 [0.02;5.76] C	0/314   649/146,855	649	314		ref
S11684 R42941	Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021	Heart defects	1st trimester	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	0.95 [0.63;1.44] excluded (control group)	23/1,430   25,755/1,965,441	25,778	1,430		ref
S11685 R42957	Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021	Heart defects	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)	1.19 [0.70;2.05]	23/1,444   37/2,724	60	1,444		ref
S13145 R50179	Marks - Duloxetine (Controls exposed to Bupropion), 2021	Cardiac Malformations	during pregnancy (anytime or not specified) excluded	retrospective cohort	exposed to other treatment, sick	Adjustment: No Monotherapy: SNRI only	1.36 [0.51;3.66] C excluded (exposition period)	6/139   13/406	19	139		ref
S11771 R43252	Anderson - SNRI, 2020	Any heart defect	1st trimester	case control	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	2.27 [1.42;3.64]	-/-   0/-	-	-		ref
S11745 R43121	Huybrechts - Duloxetine (Controls unexposed, NOS), 2020	Cardiovascular anomalies	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.29 [0.99;1.68] excluded (control group)	59/2,532   17,605/1,284,827	17,664	2,532		ref
S11746 R43142	Huybrechts - Duloxetine (Controls unexposed, sick), 2020	Cardiovascular anomalies	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)	1.41 [0.92;2.17]	59/2,532   43/2,456	102	2,532		ref
S11696 R43032	Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	Cardiac 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)	0.80 [0.47;1.38]	-/738   -/14,847	-	738		ref
S11688 R42975	Furu - Venlafaxine, 2015	Any cardiac defects	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	1.14 [0.82;1.57]	40/2,763   26,745/2,266,875	26,785	2,763		ref
S11718 R43072	Huybrechts - SNRI (Controls unexposed, NOS), 2014	Any cardiac malformations	1st trimester	cohort	unexposed (general population or NOS) excluded	Adjustment: No Monotherapy: no or not specified	1.51 [1.20;1.90] excluded (control group)	75/6,904   6,403/885,115	6,478	6,904		ref
S11719 R43076	Huybrechts - SNRI (Controls unexposed, sick), 2014	Any cardiac malformations	1st trimester	cohort	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	1.20 [0.91;1.56]	69/5,999   1,497/180,564	1,566	5,999		ref
S11693 R76990	Reis - SNRI (Controls exposed to TCA), 2010	Any cardiovascular defect	1st trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	0.82 [0.46;1.45] C excluded (control group)	20/1,351   30/1,662	50	1,351		ref
S11694 R76985	Reis - SNRI (Controls unexposed, NOS), 2010	Any cardiovascular defect	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	1.33 [0.84;2.09]	20/1,351   11,910/1,062,190	11,930	1,351		ref
S11796 R43398	Oberlander - Venlafaxine, 2008	Cardiovascular congenital defects	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	0.84 [0.12;5.98] C	1/250   512/107,320	513	250		ref
					Total	10 studies	1.30 [1.07;1.58]		41,704	15,457
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 11693, 11718, 11745, 11684, 18315, 18316

Umbrella review (other published meta-analyses)