Venlafaxine

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Bérard a, 2017	Canada 1998 - 2010	All pregnancies with continuous prescription drug insurance coverage of at least 12 months before and during pregnancy, and resulting in a singleton live birth, during the study period in the province of Quebec.	Women that had filled at least one prescription for Venlafaxine during the time window of interest (between week 21 and date of birth). (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Women that did not have filled prescription for antidepressant during the time window of of interest (between week 21 and date of birth).	419 / 141097	SNRI (venlafaxine). Duloxetine and desvenlafaxine were not included in the SNRI category as they were not on the list of medications reimbursed in Quebec during the calendar years of the study;
Bérard b (Controls exposed to TCA), 2017	Canada 1998 - 2009	Pregnancies ending with a live-born singleton with continuous prescription drug insurance coverage of at least 12 months before the 1DLMP and during pregnancy; pregnancies with a diagnosis of depression and/or anxiety or exposed to antidepressants in the 12 months before pregnancy.	Depressed/anxious pregnancies with prescription fillings for Venlafaxine (the only one Serotonin–norepinephrine reuptake inhibitor (SNRI) prescribed) dispensed during the first trimester of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Depressed/anxious pregnancies with prescription fillings for Tricyclic antidepressants (TCA) dispensed during the first trimester of gestation.	738 / 382	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bérard b (Controls unexposed, sick), 2017	Canada 1998 - 2009	Pregnancies ending with a live-born singleton with continuous prescription drug insurance coverage of at least 12 months before the 1DLMP and during pregnancy; pregnancies with a diagnosis of depression and/or anxiety or exposed to antidepressants in the 12 months before pregnancy.	Depressed/anxious pregnancies with prescription fillings for Venlafaxine (the only one Serotonin–norepinephrine reuptake inhibitor (SNRI) prescribed) dispensed during the first trimester of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnancies with a diagnosis or were treated with antidepressants in the year before their pregnancy but with no exposure to antidepressants during the first trimester of gestation.	738 / 14847	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Calderon-Margalit, 2009	USA 1996 - nr	Pregnant mothers who initiated prenatal care before 20 weeks’ gestation and planned to deliver at either one of the two study hospitals.	Pregnant women who used Venlafaxine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women who did not use psychotropic medications during pregnancy.	9 / 2493	Of the women who were taking psychotropic medications, 235 (78%) took only one medication, 51 (17%) used two medications, and 14 (5%) used three or more medications.
Chan (Controls exposed to TCA), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	Infants of women with prescription of Venlafaxine only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	exposed to other treatment, sick Infants of women with prescription of Tricyclic antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	47 / 322
Chan (Controls unexposed, general pop), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	Infants of women with prescription of Venlafaxine only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	unexposed (general population or NOS) Infants of pregnant women who were not prescribed with any antidepressant within 90 days before the last menstrual period and during the first trimester.	47 / 462377
Einarson, 2009	Canada Not specified.	Women call the service for information regarding the safety of a drug.	Pregnant women who were exposed to Venlafaxine in the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women who were not exposed to antidepressants and who had called Motherisk for information regarding nonteratogenic drugs.	154 / 928
Einarson, 2001	Italy, UK, USA, Brazil and Canada Not specfied.	Pregnant women (or their health professionals) on the safety or risk potential during pregnancy of drugs, chemicals, radiation, and infectious diseases.	Pregnant women exposed to Venlafaxine at least during organogenesis (4h and 14th week of gestation).	unexposed (general population or NOS) Pregnant women who were given nonteratogenic drugs (loperamide, echinacea, sumatriptan, and dextromethorphan).	150 / 150	Overlapping: malformations not reported because probable overlapping with Einarson 2009 (2 same malformations reported). 'The majority of the women in the venlafaxine group (70% [N=105]) took 75 mg/day of venlafaxine'
Furu, 2015	Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2010	Women who gave birth to a live singleton infant during the study period (different periods according to country).	Infants born to women who filled a prescription for Venlafaxine from 30 days before the first day of the last menstrual period until the end of the first trimester (defined as 97 days after the last menstrual period).	unexposed (general population or NOS) Infants not exposed to any antidepressant (ATC code N06A) in utero.	2763 / 2266875
Hanley, 2016	Canada 2002 - 2011	All women who delivered a live neonate in the Canadian province of British Columbia (population of 4.3 million).	A supply of Venlafaxine during pregnancy (late- or mid-pregnancy exposure). (This is a subgroup of exposure among the whole exposed group considered).	unexposed (general population or NOS) No supply of any antidepressants in the 5 months before delivery (during mid- to late pregnancy).	1390 / 310813	Venlafaxine more than 98% of SNRI. 'We excluded all women using 'other antidepressants' (such as amitriptyline, bupropion, and trazodone) from our final analyses. Women using combination SSRI and SNRI therapy were also excluded.'
Heuvelman, 2023	United Kingdom 1995 - 2017	Pregnancies in Clinical Practice Research Datalink (CPRD) with a history of depressive symptoms or use of antidepressants in the preceding year before pregnancy.	Women who had initiated or continued Lofepramine for the treatment of depressive symptoms during pregnancy.	unexposed, sick Women who did not initiate or who discontinue antidepressants during pregnancy.	818 / 16330	Dose–response relationships, sibling design (consistant results) and negative control for antidepressants use as a whole (not for the class of antidepressants).
Kjaersgaard (Controls unexposed, NOS), 2013	Denmark 1997 - 2008	All clinically recognized pregnancies in Denmark with an estimated conception and an observed pregnancy outcome during the study period.	Mother that had redeemed a prescription for Venlafaxine at any time from 30 days before conception up to 1 day before the end of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Mother that had not redeemed any prescription for antidepressant medication from 6 months before conception up to 1 day before the end of the pregnancy.	-9 / 983258	Molar or ectopic pregnancies (ICD-10: O00.0– O01.9) were excluded from the main analyses. Unexposed cohort: 1843 plus 981415 = 983258.
Kjaersgaard (Controls unexposed, sick), 2013	Denmark 1997 - 2008	All clinically recognized pregnancies in Denmark with an estimated conception and an observed pregnancy outcome during the study period.	Mother with a registry-based diagnosis of depressive disorder that had redeemed a prescription for Venlafaxine at any time from 30 days before conception up to 1 day before the end of pregnancy.	unexposed, sick Mother with a registry-based diagnosis of depressive disorder that had not redeemed any prescription for antidepressant medication from 6 months before conception up to 1 day before the end of the pregnancy.	-9 / -9	Molar or ectopic pregnancies (ICD-10: O00.0– O01.9) were excluded from the main analyses.
Kolding (Controls unexposed, disease free), 2021	Denmark 2007 - 2014	All clinically recognized singleton pregnancies with fetuses alive at the nuchal scan from 11 completed gestational weeks.	Pregnant women with two or more redeemed prescriptions of Venlafaxine from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnant women with absence of redemptions for an antidepressant in the same time window, combined with absence of former use.	847 / 353581	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Kolding (Controls unexposed, sick), 2021	Denmark 2007 - 2014	All clinically recognized singleton pregnancies with fetuses alive at the nuchal scan from 11 completed gestational weeks.	Pregnant women with two or more redeemed prescriptions of Venlafaxine from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with untreated- or well treated depression or anxiety without antidepressant use in the pregnancy (one or more redeemed prescription of an antidepressant from 365 to 183 days preconception and no redemptions between 182 days preconception through the first trimester).	847 / 6326	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Marks (Controls exposed to Bupropion), 2021	USA 2010 - 2019	Women who received at least one antidepressant prescription 3 months prior to conception through delivery.	Pregnant women with one (or more) prescription of Venlafaxine written during the time period studied. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women with one (or more) prescription of Bupropion written during the time period studied.	132 / 406	'252 women (6.8%) prescribed >1 antidepressant'=> considered as monotherapy.
Marks (Controls unexposed, sick), 2021	USA 2010 - 2019	Women who received at least one antidepressant prescription 3 months prior to conception through delivery.	Pregnant women with one (or more) prescription of Venlafaxine during the third trimester exposure. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women who took an antidepressant at some point during pregnancy but did not have a prescription for any antidepressant during the relevant period of exposure.	57 / -9	'252 women (6.8%) prescribed >1 antidepressant'=> considered as monotherapy. 'Neonatal intensive care unit admission" => not considered here because an exposure in early pregnancy could also lead to NICU admission.
Martin, 2024	Norway, Sweden and United Kingdom. 1996 - 2020	Singleton deliveries 22 weeks’ completed gestational weeks registered in the different databases during the study periods (UK: 1996-2018, Norway: 2009-2020, Sweden: 2006-2020).	Singleton deliveries with maternal Venlafaxine (without concurrent prescriptions for different antidepressants) use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden.	unexposed (general population or NOS) Singleton deliveries without maternal antidepressants use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden.	6441 / 2408707	A group ‘multiple’ (i.e drug switching or concurrent prescriptions for different antidepressants) is available => thus individual antidepressant considered as monotherapy. Unexposed numbers: Table S4.
Nulman (Controls unexposed, disease free), 2012	Canada 2001 - 2006	Pregnant women who sought counseling on the pregnancy safety of medications. (This is a subgroup of exposure among the whole exposed group considered in the study).	Depressed women who took Venlafaxine during pregnancy.	unexposed, disease free Nondepressed, healthy pregnant women who called Motherisk to inquire about nonteratogenic exposure (e.g., acetaminophen).	62 / 62	'Excluded were mothers exposed to polytherapy for depression or known teratogens, mothers with substance abuse, mothers with other psychiatric conditions, prematurity, mothers and/or children with medical conditions that may affect cognitive outcomes.'
Nulman (Controls unexposed, sick), 2012	Canada 2001 - 2006	Pregnant women who sought counseling on the pregnancy safety of medications. (This is a subgroup of exposure among the whole exposed group considered in the study).	Depressed women who took Venlafaxine during pregnancy.	unexposed, sick Depressed women who were untreated during pregnancy (discontinued pharmacotherapy before conception).	62 / 54	'Excluded were mothers exposed to polytherapy for depression or known teratogens, mothers with substance abuse, mothers with other psychiatric conditions, prematurity, mothers and/or children with medical conditions that may affect cognitive outcomes.'
Oberlander, 2008	Canada 1997 - 2002	About (92.7%) all live births (hospital and home births) in British Columbia during the study period.	Infants exposed to Venlafaxine in the first trimester of pregnancy.	unexposed (general population or NOS) Infants with no exposure to either of these drugs (Serotonin Reuptake Inhibitors (SRI) or benzodiazepine) in the first trimester of pregnancy.	250 / 107320
Ozturk, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	Pregnant women exposed to Venlafaxine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women selected from the non-teratogen exposed pregnancies in the same year.	13 / 275	'Drug exposures took place in 81% during the first trimester, and 11% in all three trimesters. Medical treatments were discontinued in most of recognized pregnancies.'=> considered as 'At least first trimester'.
Palmsten (Controls exposed to TCA), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of Venlafaxine in monotherapy during the exposure window.	exposed to other treatment, sick Pregnant women with a depression diagnosis and a dispensation of tricyclic antidepressant in monotherapy during the exposure window.	1113 / 441	Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy.
Palmsten (Controls unexposed, sick), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of Venlafaxine in monotherapy during the exposure window.	unexposed, sick Pregnant women with a depression diagnosis and no antidepressant exposure between the LMP and the end of the window.	1113 / 59219	Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy.
Palmsten b, 2013	USA 2000 - 2007	Subcohort of pregnancies in women with diagnoses for mood or anxiety disorders (between one and five months before delivery), ending in live birth among women aged 12-55.	Women with a supply of Venlafaxine monotherapy that overlapped with the delivery date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Women who had no supply of antidepressants in the five months before delivery.	763 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Rai (Controls exposed to TCA), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Venlafaxine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Children of mothers who used Clomipramine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	213 / 235	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
Rai (Controls unexposed, disease free), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Venlafaxine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free No maternal psychiatric disorder and unexposed to antidepressants	213 / 238943	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
Rai (Controls unexposed, sick), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Venlafaxine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children of mothers with psychiatric disorders (any time before the birth of the child) who did not take antidepressants during pregnancy.	213 / 12325	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
Rampono, 2009	Australia Not specified.	Pregnant women recruited prospectively and opportunistically (18–32 weeks of pregnancy) from the outpatient clinics.	Pregnant patients treated with serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants (venlafaxine only) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women untreated with antidepressants during pregnancy.	11 / 18	Maternal antenatal EPDS scores were not different between cases and controls. Mothers who were known substance abusers, or who took any medication known to alter infant behaviour (apart from those being investigated) were excluded from the study.
Richardson, 2019	The United Kingdom. 1995 - 2018	Pregnant women whose healthcare professionals contact UKTIS to discuss the potential fetal effects of maternal environmental exposures (medicines/occupational chemicals etc.) during pregnancy.	Pregnancies in which mothers had used venlafaxine at any stage of pregnancy.	unexposed (general population or NOS) Pregnancies unexposed to any antidepressant medications (matching ratio 5:1).	281 / 1405	Gestational venlafaxine exposure occurred in at least the first trimester for the majority of the venlafaxine exposed study group (n = 270/281, 96.1%). Concomitant psychiatric medication use was common among the venlafaxine exposed pregnancies.
Te Winkel, 2016	Finland, France, Israel, Italy, Netherlands and Switzerland. Not specified.	Pregnant women that called (or via healthcare professional) a Teratology information service for after individual risk counseling about exposure during pregnancy.	Pregnant women exposed to Venlafaxine during pregnancy.	unexposed (general population or NOS) Pregnant women not exposed to any known teratogen during pregnancy.	732 / 724	Number of pregnancies in the control group: 656 live births - 6 twins plus 46 spontaneous abortions plus 25 ETOPs plus 3 stillbirths.
Yaris, 2005	Turkey 1999 - 2004	Pregnant women calling for a counseling about the teratogenic risks of drugs, chemicals, and X-ray.	Women who were exposed to Venlafaxine during pregnancy for depression, anxiety, and psychotic disorders. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Women who did not use any drug while pregnant.	11 / 248	Raw data for Intrauterine exitus not reported because the nb of cases in the unexposed group not clearly stated. Raw data for premature delivery not reported because the denominator is not clearly stated.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Anderson, 2020	USA 1997 - 2011	The case infants were infants born alive or died at 20 SG or more and who had received a diagnosis of at least one selected birth defect.	The controls were live-born infants with no major birth defects who were randomly selected from hospital or state birth-certificate records from the same geographic areas.	30630 / 11478	Overlapping: this study included data obtained by Werler 2018 (gastroschisis), Lind 2013 (hypospadias) and Polen 2013 (individual malformations). 'Infants with chromosomal abnormalities or single-gene conditions were excluded.'
Dandjinou, 2019	Canada 1998 - 2015	Pregnant women with a diagnosis of gestational diabetes mellitus (GDM) identified using diagnosis codes ICD-9: 250.0–250.9, 648.0, 648.8, 790.2, 775.1 or ICD-10: E10–E14, O24, R73.0) or at least one filled prescription for an antidiabetic drug allowed during pregnancy (insulin, glyburide or metformin), both after week 20 of gestation, whichever occurred first.	Pregnant women that did not have a diagnosis of gestational diabetes mellitus (GDM) at the index date.	20905 / 209050	The 10 categories of exposure were mutually exclusive.
Kieler, 2015	Denmark, Finland, and Norway 1996 - 2007	Women with elective termination of pregnancy at 12–23 weeks of gestation.	Women that continued their pregnancy, randomly selected and matched with cases on key factors.	14902 / 148929	The (ORs) are presented for women exposed to only one type of antidepressant during the exposure period.
Laspro, 2024	USA 2013 - 2023	Newborns with oral clefts (ICD 10 codes Q35 or Q36 or Q37).	Newborns without oral clefts.	12098 / -9	P-values were calculated, while to account for multiple testing (693 hypotheses) Benjamini- Hochberg (BH) corrections were performed with a false discovery rate (Q) of 0.05.
Nakhai-Pour, 2010	Canada 1998 - 2003	Pregnant women with a diagnosis or a procedure for spontaneous abortion between the first day and the 20th week of gestation.	Randomly selected pregnant women who did not have a spontaneous abortion at or before the same gestational age as their matched case did.	5124 / 51240

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