Bupropion (All indications except smoking cessation)

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Chun-Fai-Chan (Controls exposed to other antidepressants), 2005	Canada, UK and USA Not specified	Women who contacted the teratology information services or recruited from the UK prescription event monitoring database.	Women who called either service, and that were taking bupropion for depression in the first trimester.	exposed to other treatment, sick Women who had contacted the Motherisk program, and that were exposed to other antidepressant during pregnancy.	91 / 89	Probable overlapping (despite the lack of study period) between Einarson 2009 and Chun-Fai-Chan 2005 which included more pregnancies exposed to bupropion (n=136) and that studied more outcomes. Therefore Chun-Fai-Chan 2005 used rather than Einarson 2009.
Chun-Fai-Chan (Controls unexposed, NOS), 2005	Canada, UK and USA Not specified	Women who contacted the teratology information services or recruited from the UK prescription event monitoring database.	Women who called either service, and that were taking bupropion in the first trimester.	unexposed (general population or NOS) Women who had contacted the Motherisk program, but were not exposed to any teratogens during pregnancy.	136 / 133	Probable overlapping (despite the lack of study period) between Einarson 2009 and Chun-Fai-Chan 2005 which included more pregnancies exposed to bupropion (n=136) and that studied more outcomes. Therefore Chun-Fai-Chan 2005 used rather than Einarson 2009.
Cole, 2007	USA 1995 - 2004	All women between the ages of 12 and 49, dispensed bupropion or other antidepressants and who had a live born delivery during the study period.	Infants born to women with a dispensing of bupropion during the estimated first trimester, or with a bupropion dispensing preceding the estimated first trimester with the days supplied extending into the first trimester.	exposed to other treatment, sick Infants born to women with a dispensing of antidepressants other than bupropion during the estimated first trimester, or before the first trimester with the days supplied extending into the first trimester.	1213 / 4743	The other control group (women dispensed bupropion within 18 months before delivery, or after the estimated first trimester of pregnancy and before delivery) nor reported here.
Einarson, 2009	Canada Not specified.	Women call the service for information regarding the safety of a drug.	Pregnant women who were exposed to Bupropion 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.	113 / 928
Figueroa, 2010	USA 1997 - 2006	Children and their families for which there was information on service utilization by the mother during pregnancy and by the children until they were 4 years old;	Children born to mothers with a prescription filled of Bupropion during pregnancy.	unexposed, sick Children born to depressed mothers who were not exposed to antidepressants during pregnancy	114 / 3532	For ADHD: partial overlapping between Suarez 2022 (Two databases, including MarketScan from 2003 to 2015) and Figueroa 2010 (Marketscan: 1997 - 2006) => Uncommon period study longer than common study period => the 2 studies were kept.
Huybrechts (Controls unexposed, NOS), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	Pregnant women who have had exposure to Bupropion with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women without exposure to antidepressants during the first trimester.	8856 / 885115	Exclusion of pregnancies with a diagnosis of a chromosomal abnormality and pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide).
Huybrechts (Controls unexposed, sick), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	Pregnant women who have had exposure to Bupropion with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with a diagnosis of depression without exposure to antidepressants during the first trimester.	8856 / 180564	Use of High-dimensional propensity-score data (Supplementary Table S15). Exclusion of pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide).
Jackson, 2024	U.S.A 2019 - 2022	All pregnant patients who delivered at 23 weeks of gestational age or greater at seven hospitals within a large academic health system in New York.	Prenatal exposure to a monotherapy of dopamine-norepinephrine reuptake inhibitors (DNRIs: buproprion)	unexposed, disease free No prenatal exposure to dopamine-norepinephrine reuptake inhibitors (DNRIs: buproprion).	55 / 107051
Kjaersgaard, 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 Bupropion 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.
Marks (Controls exposed to Sertraline), 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 Bupropion 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 Sertraline written during the time period studied. (This is a subgroup of exposure among the whole exposed group considered in the study)	406 / 1653	'252 women (6.8%) prescribed >1 antidepressant'=> considered as monotherapy. In the study, use of bupropion as reference group. Here, we took the inverse of ORa.
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 Bupropion 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.	172 / -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.
Ozturk, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	Pregnant women exposed to Bupropion 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.	1 / 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 (control exposed to SSRIs), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of Bupropion in monotherapy during the exposure window.	exposed to other treatment, sick Pregnant women with a depression diagnosis and a dispensation of selective serotonin reuptake inhibitor (SSRI) in monotherapy during the exposure window.	2622 / 19000	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 Bupropion 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.	2622 / 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 Bupropion 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.	1162 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Suarez (Controls unexposed, discontinuers), 2022	USA 2000 - 2015	Individuals aged 12 to 55 years with live-birth deliveries linked to infants that have insurance coverage from 3 months before the date of the estimated last menstrual period (LMP) to 1 month after delivery.	Individuals with at least 1 dispensing of bupropion from 127 days after LMP (week 19 of gestation) to delivery.	unexposed, sick Individuals that having a dispensing for bupropion in the window from 90 to 31 days prior to LMP but not during the window of 30 days prior to LMP through delivery.	19341 / 6896	For ADHD: partial overlapping between Suarez 2022 (Two databases, including MarketScan from 2003 to 2015) and Figueroa 2010 (Marketscan: 1997 - 2006) => Uncommon period study longer than common study period => the 2 studies were kept.
Suarez (Controls unexposed, general pop), 2022	USA 2000 - 2015	Individuals aged 12 to 55 years with live-birth deliveries linked to infants that have insurance coverage from 3 months before the date of the estimated last menstrual period (LMP) to 1 month after delivery.	Individuals with at least 1 dispensing of bupropion from 127 days after LMP (week 19 of gestation) to delivery.	unexposed (general population or NOS) Individuals with no antidepressants dispensing from 90 days prior to pregnancy start through the day prior to delivery.	19426 / 2981692	For ADHD: partial overlapping between Suarez 2022 (Two databases, including MarketScan from 2003 to 2015) and Figueroa 2010 (Marketscan: 1997 - 2006) => Uncommon period study longer than common study period => the 2 studies were kept.
Thyagarajan, 2012	USA 1995 - 2004	All women between the ages of 12 and 49, dispensed bupropion or other antidepressants and who had a live born delivery during the study period.	Infants born to women with a dispensing of bupropion during the estimated first trimester, or with a bupropion dispensing preceding the estimated first trimester with the days supplied extending into the first trimester.	exposed to other treatment, sick Infants born to women with a dispensing of antidepressants other than bupropion during the estimated first trimester, or before the first trimester with the days supplied extending into the first trimester.	-9 / -9	Authors utilized the same study population identified from an administrative claims database for the Cole et al. (2007) study of bupropion use during pregnancy => Methods based on Cole' publication.
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 Bupropion 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.	1 / 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.
Yeh, 2021	Taiwan 2002 - 2011	Pregnant women with bipolar disorder who were pregnant and gave birth to a child during the study period.	Pregnant women with bipolar disorder receiving dopamine norepinephrine reuptake inhibitor (i.e Bupropion) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with bipolar disorder not receiving any psychotropics before and during the pregnancy.	7 / 5243

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	'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'Overlapping: data of Lind 2013 and Alwan 2010 totally included in this larger study, thus we reported only Anderson 2020.
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.
Louik, 2014	USA and Canada 1992 - 2011	Infants with any of a wide range of malformations (infants with isolated minor defects are excluded)..	Infants without malformations.	2734 / 8611	Data available for Bupropion alone and for Bupropion in polytherapy of antidepressant and for Any Bupropion. Here, results reported for Bupropion alone.
Newport, 2016	USA 1998 - 2012	Pregnant women diagnosed by their obstetrical care providers using ACOG– recommended diagnostic criteria for hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome.	No history of hypertension.	86 / 600	Most study participants were treated with at least 1 psychotropic agent during pregnancy (n = 607, 88.5%) with antidepressant exposure the most frequent (n=489, 71.3%) => Non exposure considered as "exposed to other treatments".

master protocol