Tricyclic antidepressants updated on 07-01-2025

Limb defects

id	Study   Auto Chan (Controls exposed to SSRIs), 2024Chan (Controls unexposed, general pop), 2024Chan (Controls unexposed, sick), 2024Bérard (Controls unexposed, sick), 2017Ban (Controls exposed to SSRIs), 2014Ban (Controls unexposed, disease free), 2014Ban (Controls unexposed, sick), 2014Simon (Controls exposed to SSRIs), 2002Simon (Controls unexposed, NOS), 2002	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.
S18161 R76384	Chan (Controls exposed to SSRIs), 2024	Musculoskeletal malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	1.75 [0.68;4.48] C excluded (control group)	7/322   12/956	19	322		ref
S18156 R76338	Chan (Controls unexposed, general pop), 2024	Musculoskeletal malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: TCA only	2.08 [0.96;4.52] excluded (control group)	7/322   5,767/462,377	5,774	322		ref
S18157 R76349	Chan (Controls unexposed, sick), 2024	Musculoskeletal malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: TCA only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	2.09 [0.63;6.94]	3/181   68/4,413	71	181		ref
S11052 R40986	Bérard (Controls unexposed, sick), 2017	Musculoskeletal system malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: TCA only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.84 [0.49;1.44]	-/382   -/14,847	-	382		ref
S10937 R40704	Ban (Controls exposed to SSRIs), 2014	Limb malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	1.34 [0.72;2.52] C excluded (control group)	14/2,428   33/7,683	47	2,428		ref
S10938 R40720	Ban (Controls unexposed, disease free), 2014	Limb malformations	1st trimester	retrospective cohort (claims database)	unexposed, disease free excluded	Adjustment: Yes Monotherapy: TCA only	1.04 [0.61;1.77] excluded (control group)	14/2,428   1,750/325,294	1,764	2,428		ref
S10939 R40742	Ban (Controls unexposed, sick), 2014	Limb malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: TCA only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.08 [0.60;1.93]	14/2,428   71/13,432	85	2,428		ref
S10935 R40678	Simon (Controls exposed to SSRIs), 2002	Skeletal malformations	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	1.79 [0.32;9.86] C excluded (control group)	4/209   2/185	6	209		ref
S10936 R40694	Simon (Controls unexposed, NOS), 2002	Skeletal malformations	during pregnancy (anytime or not specified) excluded	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: TCA only	0.80 [0.21;3.00] excluded (exposition period)	4/209   5/209	9	209		ref
					Total	3 studies	1.02 [0.70;1.49]		156	2,991
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 10935, 10937, 10938, 18161, 18156