Mirtazapine

Exposed non-exposed, cohort studies

Study Country
Study period
Study design		 Data source Exposure definition Non-exposure definition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Chan (Controls exposed to SSRIs)
2024 		China
2003 - 2018
retrospective cohort (claims database) 		The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents. 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. 		1st trimester 76 / 956
Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.
Chan (Controls unexposed, pop general)
2024 		China
2003 - 2018
retrospective cohort (claims database) 		The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents. 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. 		1st trimester 76 / 462377
Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.
Djulus (Controls exposed to other antidepressants)
2006 		Australia, Canada, Israel, Italy, United Kingdom and USA.
2002 - 2005
prospective cohort 		The Motherisk Program (Toronto, Canada), Israel Teratogen Information Service (Jerusalem, Israel), Mothersafe Program (Sydney, Australia), Pregnancy Riskline (Farmington, U.S.A.), Telefono Rosso (Rome, Italy), the Drug Safety Research Unit (UK). 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. 		1st trimester 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
During the initial telephone contact with mother, details of exposure and concurrent exposures were recorded on a standardized questionnaire. A specific, detailed questionnaire was sent to each prescribing general practitioner regarding drug history.
Djulus (Controls unexposed, disease free)
2006 		Australia, Canada, Israel, Italy, United Kingdom and USA.
2002 - 2005
prospective cohort 		The Motherisk Program (Toronto, Canada), Israel Teratogen Information Service (Jerusalem, Israel), Mothersafe Program (Sydney, Australia), Pregnancy Riskline (Farmington, U.S.A.), Telefono Rosso (Rome, Italy), the Drug Safety Research Unit (UK). 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. 		1st trimester 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
During the initial telephone contact with mother, details of exposure and concurrent exposures were recorded on a standardized questionnaire. A specific, detailed questionnaire was sent to each prescribing general practitioner regarding drug history.
Einarson
2009 		Canada
Not specified.
prospective cohort 		The Motherisk Program, a teratogenic information service. 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. 		1st trimester 68 / 928
During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire.
Gungor (Controls exposed to SSRI)
2019 		Turkey
2015 - 2018
prospective cohort 		Not specified 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. 		during pregnancy (anytime or not specified) 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.
Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.
Gungor (Controls unexposed, disease free)
2019 		Turkey
2015 - 2018
prospective cohort 		Not specified Pregnant women medicated with mirtazapine as a single treatment. unexposed, disease free
Healthy women with no current nor previous psychiatric disorder history. 		during pregnancy (anytime or not specified) 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...
Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.
Gungor (Controls unexposed, sick)
2019 		Turkey
2015 - 2018
prospective cohort 		Not specified Pregnant women medicated with mirtazapine as a single treatment. unexposed, sick
Pregnant women with unmedicated psychiatric disorder. 		during pregnancy (anytime or not specified) 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.
Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.
Heuvelman
2023 		United Kingdom
1995 - 2017
retrospective cohort (claims database) 		The UK Clinical Practice Research Datalink, a large, ongoing database of anonymised primary care medical records for patients registered with a general practice in the United Kingdom. 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. 		during pregnancy (anytime or not specified) 552 / 16330 Dose–response relationships, sibling design and negative control for antidepressants use as a whole (not for the class of antidepressants).
The Clinical Practice Research Datalink (CPRD) contains an extensive code list to identify the name, formulation and dose of medications, which are mandatory fields in the prescription electronic record (according to protocol).
Källen
2013 		Sweden
1996 - 2011
population based cohort retrospective 		Swedish Medical Birth Register 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. 		1st trimester, early pregnancy 585 / 1575847
The exposure data are either based on midwife interviews from the first antenatal visit (usually during weeks 10–12) or on linkage with a prescribed drug register.
Kolding (Controls unexposed, disease free)
2021 		Denmark
2007 - 2014
population based cohort retrospective 		Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database. 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. 		1st trimester 120 / 353581 'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.
Kolding (Controls unexposed, sick)
2021 		Denmark
2007 - 2014
population based cohort retrospective 		Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database. 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). 		1st trimester 120 / 6326 'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.
Lee (Controls exposed to SSRI)
2025 		China
2003 - 2018
retrospective cohort (claims database) 		The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong. 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. 		during pregnancy (anytime or not specified) 77 / 1465
The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.
Lee (Controls unexposed, general pop)
2025 		China
2003 - 2018
retrospective cohort (claims database) 		The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong. 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. 		during pregnancy (anytime or not specified) 77 / 463440
The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.
Martin
2024 		Norway, Sweden and United Kingdom.
1996 - 2020
population based cohort retrospective 		The UK’s Clinical Practice Research Datalink (CPRD), the Norway’s Medical Birth Registry and the Sweden’s Medical Birth Register. 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. 		during pregnancy (anytime or not specified) 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.
In the UK, prescription data were based on the prescriptions written by general practitioners (CPRD GOLD), whereas in Norway and Sweden, dispensation of prescription drugs from all ambulatory pharmacies was used (Norwegian Prescription Database, and Swedish Prescribed Drug Register).
Ostenfeld
2022 		Denmark
1997 - 2016
population based cohort retrospective 		Population-based cohort based on the Medical Birth Register and/or the National Hospital Register, the Danish Civil Registration System and the Register of Medicinal Product Statistics. 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. 		1st and 2nd trimester, 1st trimester, during pregnancy (anytime or not specified) 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.
Data on pregnancies ending in live births and stillbirths were collected from The Medical Birth Register. Data on pregnancies with abortive outcome before 22 weeks of gestation were obtained from The National Hospital Register.
Ozturk
2016 		Turkey
2007 - 2012
prospective cohort 		An observational cohort study based on a prenatal consultation service. 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. 		at least 1st trimester 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'.
At the first contact, initiated via gynecologists, a detailed patient history form was used to notably record all drug exposures (dose, duration and timing in pregnancy).
Palmsten a (control exposed to SSRIs)
2013 		USA
2000 - 2007
retrospective cohort (claims database) 		The US nationwide Medicaid Analytic eXtract (MAX). 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. 		2nd and/or 3rd trimester 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.
Outpatient pharmacy-dispensing data.
Palmsten a (Controls unexposed, sick)
2013 		USA
2000 - 2007
retrospective cohort (claims database) 		The US nationwide Medicaid Analytic eXtract (MAX). 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. 		2nd and/or 3rd trimester 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.
Outpatient pharmacy-dispensing data.
Palmsten b
2013 		USA
2000 - 2007
retrospective cohort (claims database) 		The Medicaid Analytic eXtract (MAX) data 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. 		late pregnancy 129 / 69044 Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Data of prescription.
Winterfeld (Controls exposed to SSRI)
2015 		Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK
1995 - 2011
prospective cohort 		11 Teratology Information Services (TIS) of Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK. 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). 		1st trimester, during pregnancy (anytime or not specified) 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).
Medication exposure (indication, timing in pregnancy, duration, dose, and concomitant medication) was collected at initial Teratology Information Services (TIS) contact.
Winterfeld (Controls unexposed, NOS)
2015 		Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK
1995 - 2011
prospective cohort 		11 Teratology Information Services (TIS) of Czech Republic, Finland, Israel, Italy, Switzerland, The Netherlands, Turkey and UK. 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). 		1st trimester, during pregnancy (anytime or not specified) 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).
Medication exposure (indication, timing in pregnancy, duration, dose, and concomitant medication) was collected at initial Teratology Information Services (TIS) contact.
Yaris
2005 		Turkey
1999 - 2004
prospective cohort 		Toxicology Information and Follow-up Service 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. 		during pregnancy (anytime or not specified) 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.
Data surveyed by the interviews.

Case-control studies

Study Country
Study period
Study design		 Data source Case Control Exposition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Anderson
2020 		USA
1997 - 2011
case control 		The National Birth Defects Prevention Study (NBDPS), a US population-based, multisite case-control study. 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. Information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants, conducted 6 weeks to 24 months after the EDD. 1st trimester 30630 / 11478 'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'
Case infants were ascertained through population-based birth-defects surveillance systems in 10 U.S. states. Controls were selected randomly from the same geographic areas. Clinical data were abstracted from medical records and classified by clinician geneticists and other clinicians.
Kieler
2015 		Denmark, Finland, and Norway
1996 - 2007
nested case control 		National registers of Denmark, Finland, and Norway. 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. The prescription registers include data on dispensed item, substance, brand name, and formulation, together with date of dispensing for over 95% of the total outpatient population. 3 months (or more) before pregnancy or during pregnancy, during pregnancy (anytime or not specified) 14902 / 148929 The (ORs) are presented for women exposed to only one type of antidepressant during the exposure period.
In the registers the diagnoses and pregnancy complications are classified according to the national version of the International Classification of Diseases (ICD).
Laspro
2024 		USA
2013 - 2023
nested case control 		EPIC Cosmos, a database incorporating health information of 180 million patients, throughout the United States from approximately 180 US institutions utilizing EPIC medical records. Newborns with oral clefts (ICD 10 codes Q35 or Q36 or Q37). Newborns without oral clefts. Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy. during pregnancy (anytime or not specified) 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.
Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.

Risk of bias: : NA;   : low;   : moderate;   : serious;   : critical;   : unclear;  

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