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

ASD (Autism spectrum disorder): Diagnosis

id	Study   Auto Heuvelman - Venlafaxine, 2023Suarez - SNRI (Controls unexposed, discontinuers), 2022Suarez - SNRI (Controls unexposed, general pop), 2022Hagberg - SNRI (Controls exposed to TCA), 2018Hagberg - SNRI (Controls unexposed, disease free), 2018Hagberg - SNRI (Controls unexposed, sick), 2018Rai - Venlafaxine (Controls exposed to TCA), 2017Rai - Venlafaxine (Controls unexposed, disease free), 2017Rai - Venlafaxine (Controls unexposed, sick), 2017Boukhris - SNRI (Controls exposed to TCA), 2016Boukhris - SNRI (Controls unexposed, NOS), 2016Sørensen - SNRI (Controls exposed to TCA), 2013Sørensen - SNRI (Controls unexposed, NOS), 2013	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.
S18387 R77528	Heuvelman - Venlafaxine, 2023	Autism spectrum disorder - Validated Read code list among primary care clinical and referral records - Mean age at end of follow-up 10.04 years, range 4–22 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Partial overlapping Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.46 [0.78;2.73]	-/818   -/16,330	-	818		ref
S18333 R77337	Suarez - SNRI (Controls unexposed, discontinuers), 2022	Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year 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)	1.79 [1.08;2.99]	66/8,540   28/4,899	94	8,540		ref
S18334 R77348	Suarez - SNRI (Controls unexposed, general pop), 2022	Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year of age	2nd and/or 3rd trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.04 [0.79;1.37] excluded (control group)	67/8,659   11,270/2,910,114	11,337	8,659		ref
S11813 R43417	Hagberg - SNRI (Controls exposed to TCA), 2018	Autism spectrum disorder (diagnostic code including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD)) - Median diagnosis 5.8 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only Partial overlapping	0.51 [0.29;0.92] C excluded (control group)	13/1,246   98/4,856	111	1,246		ref
S11814 R43418	Hagberg - SNRI (Controls unexposed, disease free), 2018	Autism spectrum disorder (diagnostic code including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD)) - Median diagnosis 5.8 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, disease free excluded	Adjustment: Yes Matched Monotherapy: SNRI only Partial overlapping	1.03 [0.60;1.78] excluded (control group)	13/1,246   1,500/154,107	1,513	1,246		ref
S11815 R43419	Hagberg - SNRI (Controls unexposed, sick), 2018	Autism spectrum disorder (diagnostic code including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD)) - Median diagnosis 5.8 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: No Monotherapy: SNRI only Partial overlapping Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.69 [0.39;1.21] C	13/1,246   196/12,994	209	1,246		ref
S11816 R43420	Rai - Venlafaxine (Controls exposed to TCA), 2017	Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) - At 4-17 years	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	0.75 [0.34;1.64] C excluded (control group)	11/213   16/235	27	213		ref
S11817 R43422	Rai - Venlafaxine (Controls unexposed, disease free), 2017	Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) - At 4-17 years	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: SNRI only	2.61 [1.42;4.79] C excluded (control group)	11/213   4,889/238,943	4,900	213		ref
S11818 R43424	Rai - Venlafaxine (Controls unexposed, sick), 2017	Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) - At 4-17 years	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: Yes Monotherapy: SNRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	1.81 [0.89;3.71]	11/213   353/12,325	364	213		ref
S11702 R43053	Boukhris - SNRI (Controls exposed to TCA), 2016	Autism spectrum disorder (ICD-9 codes 299.0, 299.8, 299.9; ICD-10 codes F84.0, F84.1, F84.5, F84.8, F84.9) - End follow-up: mean 6.2 years (median 7.0 years)	2nd and/or 3rd trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	0.51 [0.07;3.65] C excluded (control group)	2/447   2/229	4	447		ref
S11703 R43054	Boukhris - SNRI (Controls unexposed, NOS), 2016	Autism spectrum disorder (ICD-9 codes 299.0, 299.8, 299.9; ICD-10 codes F84.0, F84.1, F84.5, F84.8, F84.9) - End follow-up: mean 6.2 years (median 7.0 years)	2nd and/or 3rd trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	1.04 [0.20;5.46]	2/447   1,023/142,924	1,025	447		ref
S11782 R43353	Sørensen - SNRI (Controls exposed to TCA), 2013	Autism spectrum disorder (ICD-10, codes F84.0, F84.1, F84.5, F84.8, and F84.9) - At 4-14 years (mean 8.8 years)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	0.74 [0.27;2.00] C excluded (control group)	7/673   9/642	16	673		ref
S11783 R43356	Sørensen - SNRI (Controls unexposed, NOS), 2013	Autism spectrum disorder (ICD-10, codes F84.0, F84.1, F84.5, F84.8, and F84.9) - At 4-14 years (mean 8.8 years)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	1.70 [0.80;3.50]	7/673   5,333/646,782	5,340	673		ref
					Total	6 studies	1.36 [0.96;1.94]		7,032	11,937
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 11782, 11702, 11816, 11817, 11813, 11814, 18334