Mirtazapine

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Chan (Controls exposed to SSRIs), 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 Mirtazapine 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 Selective-serotonin-reuptake-inhibitors (SSRI) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	76 / 956
Chan (Controls unexposed, pop general), 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 Mirtazapine 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.	76 / 462377
Djulus (Controls exposed to other antidepressants), 2006	Australia, Canada, Israel, Italy, United Kingdom and USA. 2002 - 2005	Pregnant women that called for a Teratogen Information Service or pregnant women recruited through an academic and independent medical charity.	Pregnant women exposed to mirtazapine during pregnancy.	exposed to other treatment, sick Disease-matched pregnant women taking other antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or tricyclic antidepressants.	104 / 104	Exclusion of chromosomal defects and genetic disorders from the primary analysis of major structural defects. The mean ± SD daily dose of mirtazapine was 30 ± 12 mg
Djulus (Controls unexposed, disease free), 2006	Australia, Canada, Israel, Italy, United Kingdom and USA. 2002 - 2005	Pregnant women that called for a Teratogen Information Service or pregnant women recruited through an academic and independent medical charity.	Pregnant women exposed to mirtazapine during pregnancy.	unexposed, disease free Nondepressed women who contacted the participating centers for exposures known to be nonteratogenic, such as acetaminophen, cold medications, hair dyes, cleaning products, antacids, antibiotics, and antihistamines.	104 / 104	Exclusion of chromosomal defects and genetic disorders from the primary analysis of major structural defects. The mean ± SD daily dose of mirtazapine was 30 ± 12 mg
Einarson, 2009	Canada Not specified.	Women call the service for information regarding the safety of a drug.	Pregnant women who were exposed to Mirtazapine 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.	68 / 928
Gungor (Controls exposed to SSRI), 2019	Turkey 2015 - 2018	The pregnancies in women older than 18 with live and singleton births.	Pregnant women medicated with mirtazapine as a single treatment.	exposed to other treatment, sick Pregnant women medicated with selective serotonine reuptake inhibitor (SSRI) as a single treatment.	16 / 40	The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder... The mean dosage of mirtazapine was 21.09 ± 8.75 mg/per day.
Gungor (Controls unexposed, disease free), 2019	Turkey 2015 - 2018	The pregnancies in women older than 18 with live and singleton births.	Pregnant women medicated with mirtazapine as a single treatment.	unexposed, disease free Healthy women with no current nor previous psychiatric disorder history.	16 / 23	The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder...
Gungor (Controls unexposed, sick), 2019	Turkey 2015 - 2018	The pregnancies in women older than 18 with live and singleton births.	Pregnant women medicated with mirtazapine as a single treatment.	unexposed, sick Pregnant women with unmedicated psychiatric disorder.	16 / 23	The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder... The mean dosage of mirtazapine was 21.09 ± 8.75 mg/per day.
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 Mirtazapine for the treatment of depressive symptoms during pregnancy.	unexposed, sick Women who did not initiate or who discontinue antidepressants during pregnancy.	552 / 16330	Dose–response relationships, sibling design and negative control for antidepressants use as a whole (not for the class of antidepressants).
Källen, 2013	Sweden 1996 - 2011	Nearly all births in Sweden, based on standardized medical records, used in the whole country.	Infants whose mothers used Mirtazapine 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.	585 / 1575847
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 Mirtazapine 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.	120 / 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 Mirtazapine 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).	120 / 6326	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Lee (Controls exposed to SSRI), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	Women filling at least one prescription of Mirtazapine only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	exposed to other treatment, sick Women filling at least one prescription of any selective serotonin reuptake inhibitors (SSRI) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	77 / 1465
Lee (Controls unexposed, general pop), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	Women filling at least one prescription of Mirtazapine only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	unexposed (general population or NOS) Women who were not prescribed with any antidepressant during index pregnancy.	77 / 463440
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 Mirtazapine (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.	2658 / 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.
Ostenfeld, 2022	Denmark 1997 - 2016	All pregnancies in Denmark registered in the Medical Birth Register and/or the National Hospital Register.	At least one filled prescription for mirtazapine (ATC: N06AX11) with the date of filled prescription considered the first day of exposure.	unexposed (general population or NOS) No filled prescription for mirtazapine.	1945 / 7780	For Mirtazapine: overlapping for Early intrauterine death between Ostenfeld 2022 (1997-2016) and Kjaersgaard, 2013 (1997-2008), based on the same databases. Ostenfeld that use adjustment and based on a longer study period reported rather than Kjaersgaard.
Ozturk, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	Pregnant women exposed to Mirtazapine 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.	7 / 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 a (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 Mirtazapine 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.	253 / 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 a (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 Mirtazapine 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.	253 / 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 Mirtazapine 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.	129 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Winterfeld (Controls exposed to SSRI), 2015	Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK 1995 - 2011	Pregnant women who themselves or whose physician contacted 1 of the 11 participating Teratology Information Services (TIS) during the study period.	Pregnant women who were exposed to mirtazapine.	exposed to other treatment, sick Pregnant women who were exposed to any SSRI (control subjects with a psychiatric condition).	357 / 357	The median daily mirtazapine dose was 30 mg (interquartile range [IQR], 15–30 mg). In the SSRI control group: citalopram (n = 94), fluoxetine (n = 89), sertraline (n = 64), escitalopram (n = 59), paroxetine (n = 42), and fluvoxamine (n = 9).
Winterfeld (Controls unexposed, NOS), 2015	Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK 1995 - 2011	Pregnant women who themselves or whose physician contacted 1 of the 11 participating Teratology Information Services (TIS) during the study period.	Pregnant women who were exposed to mirtazapine.	unexposed (general population or NOS) Pregnant women who were at no time during pregnancy exposed to any known major teratogens or fetotoxicants or to any antidepressant (general control subjects).	357 / 357	The median daily mirtazapine dose was 30 mg (interquartile range [IQR], 15–30 mg). In the SSRI control group: citalopram (n = 94), fluoxetine (n = 89), sertraline (n = 64), escitalopram (n = 59), paroxetine (n = 42), and fluvoxamine (n = 9).
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 Mirtazapine 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.	7 / 248	Raw data for Intrauterine exitus not reported because the number 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	'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'
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.

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