Duloxetine - Medication and Pregnancy KB

Duloxetine

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Ankarfeldt (Controls unexposed, NOS), 2023	Sweden and Denmark 2004 - 2016	All pregnancies with a registered live birth from 2004 to 2016, identified via the national Danish and Swedish medical birth registers.	Pregnant women with at least one redeemed prescription of duloxetine (ATC: N06AX21) from a community pharmacy during pregnancy (early exposure and/or late exposure) (and no SSRI or venlafaxine comedication).	unexposed (general population or NOS) Pregnant women with not exposed to duloxetine during pregnancy and from 90 days prior to last menstrual period.	1589 / 2080880	1589 and 450 were duloxetine exposed in early and late pregnancies, respectively. Few overlapping between Reis 2010 (1995 - 2007) and Ankarfeldt 2023 (2004 - 2016) => the 2 studies were kept.
Ankarfeldt (Controls unexposed, sick), 2023	Sweden and Denmark 2004 - 2016	All pregnancies with a registered live birth from 2004 to 2016, identified via the national Danish and Swedish medical birth registers.	Pregnant women with at least one redeemed prescription of duloxetine (ATC: N06AX21) from a community pharmacy during pregnancy (early exposure and/or late exposure) (and no SSRI or venlafaxine comedication).	unexposed, sick Pregnant women who have discontinued duloxetine, i.e with at least one redeemed prescription of duloxetine between 365 days prior to LMP, but not during the exposure-time window.	1589 / 2839	1589 and 450 were duloxetine exposed in early and late pregnancies, respectively. Few overlapping between Reis 2010 (1995 - 2007) and Ankarfeldt 2023 (2004 - 2016) => the 2 studies were kept.
Ankarfeldt a (Controls unexposed, NOS), 2021	Sweden and Denmark 2004 - 2016	All live and stillbirths of women with a valid personal identification number aged 18 and above, during the study period.	At least one redeemed prescription of duloxetine from Last menstrual period (LMP) to 90 days after LMP for malformations or to the end of pregnancy (for stillbirth).	unexposed (general population or NOS) No redeemed prescription of duloxetine in the exposure time window (women with duloxetine exposure from 90 days prior to LMP but no exposure from LMP to 90 days after LMP were excluded).	1512 / 2074652	Cohort for stillbirths: 1668 exposed; 2130495 unexposed.For malformations: exclusion mothers with a redeemed prescription for a teratogenic drug in the period from LMP to 90 days post LMP.
Ankarfeldt a (Controls unexposed, sick), 2021	Sweden and Denmark 2004 - 2016	All live and stillbirths of women with a valid personal identification number aged 18 and above, during the study period.	At least one redeemed prescription of duloxetine from Last menstrual period (LMP) to 90 days after LMP for malformations or to the end of pregnancy (for stillbirth).	unexposed, sick Duloxetine discontinuers: at least one redeemed prescription of duloxetine between 365 days prior to LMP to LMP and not during pregnancy.	1512 / 2876	Cohort for stillbirths: 1668 exposed; 2815 discontinuers.For malformations: exclusion mothers with a redeemed prescription for a teratogenic drug in the period from LMP to 90 days post LMP.
Ankarfeldt b (Controls unexposed, sick), 2021	Denmark 2004 - 2016	All pregnancies in Denmark with a hospital contact encounter during the study period were eligible.	At least one redeemed prescription of duloxetine from 30 days prior to last menstrual period (LMP) to 140 days post LMP, or the end of the pregnancy, whichever came first.	unexposed, sick Duloxetine discontinuers: at least one redeemed prescription of duloxetine between 365 days prior to LMP to 30 days prior to LMP, but no redeemed prescription of duloxetine in the exposure time window.	1212 / 1418	Overlapping: partial overlapping between Ankarfeldt 2021b (2004 - 2016) and Kjaersgaard 2013 (1997 - 2008). Because the 2 study periods are longer than the common period, the 2 studies were kept.
Ankarfeldt b Controls unexposed, NOS), 2021	Denmark 2004 - 2016	All pregnancies in Denmark with a hospital contact encounter during the study period were eligible.	At least one redeemed prescription of duloxetine from 30 days prior to last menstrual period (LMP) to 140 days post LMP, or the end of the pregnancy, whichever came first.	unexposed (general population or NOS) Duloxetine non-exposed: no redeemed prescriptions of duloxetine in the exposure time window;	1212 / 1018745	Overlapping: partial overlapping between Ankarfeldt 2021b (2004 - 2016) and Kjaersgaard 2013 (1997 - 2008). Because the 2 study periods are longer than the common period, the 2 studies were kept.
Bahat, 2020	Israel 2001 - 2015	Pregnancies of women, who consulted the Israeli Teratology Information Service (TIS) during the study period.	Pregnant women counseled for duloxetine exposure in the first trimester.	unexposed (general population or NOS) Pregnant women counseled for non-teratogenic exposure in pregnancy.	128 / 511	Major congenital anomalies excluding genetic or cytogenetic not reported because number of cases, exposures and exclusions not provided.
Huybrechts (Controls unexposed, NOS), 2020	USA 2004 - 2013	Pregnant women 18 to 55 years of age and their liveborn infants.	Pregnant women who filled at least one outpatient prescription for duloxetine during the etiologically relevant window.	unexposed (general population or NOS) Pregnant women not exposed to duloxetine during the etiologically relevant exposure window.	2532 / 1284827	Exclusion of pregnancies exposed to a known teratogenic drug (warfarin, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) 1st trimester. Partial overlapping for preeclampsia and cardiac malfo (Palmsten 2013, Huybrechts 2014 and 2020)
Huybrechts (Controls unexposed, sick), 2020	USA 2004 - 2013	Pregnant women 18 to 55 years of age and their liveborn infants.	Pregnant women who filled at least one outpatient prescription for duloxetine during the etiologically relevant window.	unexposed, sick Pregnant women exposed to duloxetine before but not during pregnancy (≥1 duloxetine dispensing between 6 months and 60 days before LMP but not during first trimester).	2532 / 2456	Exclusion of pregnancies exposed to a known teratogenic drug (warfarin, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) 1st trimester. Partial overlapping for preeclampsia and cardiac malfo (Palmsten 2013, Huybrechts 2014 and 2020)
Källen, 2013	Sweden 1996 - 2011	Nearly all births in Sweden, based on standardized medical records, used in the whole country.	Infants whose mothers used Duloxetine in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants in population whose mothers used at least one of a central nervous system active drugs (less than 3%) or weren't exposed in early pregnancy.	286 / 1575847	RR calculated with observed/expected numbers. Partial overlapping for major malformations between Kallen 2013 (1996- 2011) and Ankarfeldt 2021a (2004-2016): because the non common study periods are longer than the common period, the 2 studies were kept.
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 Duloxetine 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. Partial overlapping between Ankarfeldt 2021b (2004 - 2016) and Kjaersgaard 2013 (1997 - 2008).
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 Duloxetine 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. Partial overlapping between Ankarfeldt 2021b (2004 - 2016) and Kjaersgaard 2013 (1997 - 2008).
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 Duloxetine 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.	139 / 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 Duloxetine 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.	59 / -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 Duloxetine (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.	1602 / 2408707	Overlapping: Martin 2024 and Ankarfeld 2023 both studied Preterm and SGA with Swedish databases (and other databases) => these outcomes not reported here (but reported for Norway and UK in separately); but Apgar score (no overlapping) reported here.
Martin - Norway, 2024	Norway 2009 - 2020	Singleton deliveries 22 weeks’ completed gestational weeks registered in the different databases during the study period.	Singleton deliveries with maternal Duloxetine (without concurrent prescriptions for different antidepressants) use during pregnancy proxied by dispensations.	unexposed (general population or NOS) Singleton deliveries without maternal antidepressants use during pregnancy proxied by dispensations.	115 / 662309	Overlapping: Martin 2024 and Ankarfeld 2023 both studied Preterm and SGA with Swedish databases (and other databases) with large common study periods => SE data not reported but Norway and UK reported here separately.
Martin - UK, 2024	United Kingdom. 1996 - 2018	Singleton deliveries 22 weeks’ completed gestational weeks registered in the different databases during the study period.	Singleton deliveries with maternal Duloxetine (without concurrent prescriptions for different antidepressants) use during pregnancy proxied by prescriptions.	unexposed (general population or NOS) Singleton deliveries without maternal antidepressants use during pregnancy proxied by prescriptions.	71 / 330696	Unexposed numbers: Table S4. Overlapping: Martin 2024 and Ankarfeld 2023 both studied Preterm and SGA with Swedish databases (and other databases) with large common study periods => SE data not reported but Norway and UK reported here separately.
Ozturk, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	Pregnant women exposed to Duloxetine 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.	3 / 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, 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of Duloxetine 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.	-9 / 59219	Nb of exposures not provided by authors. 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.

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.'

master protocol