Mirtazapine updated on 07-01-2025

Major congenital malformations

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S18313
R77116		 Chan (Controls exposed to SSRIs), 2024 Any major malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.89 [0.35;2.28] C
excluded (control group) 		5/76   70/956 75 76
ref
S18314
R77119		 Chan (Controls unexposed, pop general), 2024 Any major malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.35 [0.54;3.34] 5/76   22,628/462,377 22,633 76
ref
S12950
R49146		 Ostenfeld, 2022 Major congenital malformations 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.81 [0.55;1.20] 31/895   152/3,580 183 895
ref
S11769
R43248		 Anderson, 2020 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.19 [0.03;1.02] C 2/6   30,628/42,102 30,630 6
ref
S11789
R43374		 Ozturk, 2016 Major congenital defects at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 9.90 [0.43;229.94] C 0/4   3/246 3 4
ref
S12913
R48984		 Winterfeld (Controls exposed to SSRI), 2015 Major birth defects, 1st-trimester exposure 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: no or not specified 0.80 [0.35;1.86]
excluded (control group) 		10/292   13/307 23 292
ref
S12914
R48991		 Winterfeld (Controls unexposed, NOS), 2015 Major birth defects, 1st-trimester exposure 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.79 [0.64;4.99] 10/292   6/309 16 292
ref
S11838
R43453		 Källen, 2013 Relatively severe malformations 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.10 [0.70;1.71] 20/585   -/- - 585
ref
S11750
R43192		 Einarson, 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.09 [0.25;4.72] C 2/68   25/928 27 68
ref
S12911
R48960		 Djulus (Controls exposed to other antidepressants), 2006 Major malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: no or not specified 2.19 [0.19;24.61] C
excluded (control group) 		2/77   1/83 3 77
ref
S12910
R48955		 Djulus (Controls unexposed, disease free), 2006 Major malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No Matched Monotherapy: no or not specified 1.20 [0.17;8.72] C 2/77   2/92 4 77
ref
Total 8 studies 1.02 [0.72;1.43] 53,496 2,003
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Chan (Controls unexposed, pop general), 2024Chan, 2024 1 1.35[0.54; 3.34]22,6337611%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ostenfeld, 2022Ostenfeld, 2022 0.81[0.55; 1.20]18389535%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 0.19[0.03; 1.02]30,63064%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Ozturk, 2016Ozturk, 2016 9.90[0.43; 229.94]341%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Winterfeld (Controls unexposed, NOS), 2015Winterfeld, 2015 2 1.79[0.64; 4.99]162929%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Källen, 2013Källen, 2013 1.10[0.70; 1.71]-58531%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Einarson, 2009Einarson, 2009 1.09[0.25; 4.72]27685%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Djulus (Controls unexposed, disease free), 2006Djulus, 2006 3 1.20[0.17; 8.72]4773%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (8 studies) I2 = 20% 1.02[0.72; 1.43]53,4962,0030.020.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, pop general; 2: Controls unexposed, NOS; 3: Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.79; 1.33]22,8661,9970%NAChan (Controls unexposed, pop general), 2024 Ostenfeld, 2022 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Källen, 2013 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 7 case control studiescase control studies 0.19[0.03; 1.02]30,6306 -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.02[0.72; 1.43]53,4962,00320%NAChan (Controls unexposed, pop general), 2024 Ostenfeld, 2022 Anderson, 2020 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Källen, 2013 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 8 Tags Adjustment   - No  - No 1.09[0.41; 2.92]30,68044742%NAAnderson, 2020 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 5   - Yes  - Yes 0.96[0.72; 1.27]22,8161,5560%NAChan (Controls unexposed, pop general), 2024 Ostenfeld, 2022 Källen, 2013 3 MatchedMatched 1.64[0.66; 4.09]203690%NAWinterfeld (Controls unexposed, NOS), 2015 Djulus (Controls unexposed, disease free), 2006 2 Monotherapy   - no or not specified  - no or not specified 1.00[0.76; 1.31]2331,9210%NAOstenfeld, 2022 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Källen, 2013 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 6   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.58[0.08; 3.92]53,2638275%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 2 All studiesAll studies 1.02[0.72; 1.43]53,4962,00320%NAChan (Controls unexposed, pop general), 2024 Ostenfeld, 2022 Anderson, 2020 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Källen, 2013 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 80.020.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.81.9260.000Chan (Controls unexposed, pop general), 2024Ostenfeld, 2022Anderson, 2020Ozturk, 2016Winterfeld (Controls unexposed, NOS), 2015Källen, 2013Einarson, 2009Djulus (Controls unexposed, disease free), 2006

Asymetry test p-value = 0.5442 (by Egger's regression)

slope=-0.1599 (0.2707); intercept=0.4654 (0.7242); t=0.6426; p=0.5442

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 12911, 12913, 18313

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.02[0.72; 1.43]53,5072,00320%NAChan (Controls unexposed, pop general), 2024 Ostenfeld, 2022 Anderson, 2020 Ozturk, 2016 Winterfeld (Controls unexposed, NOS), 2015 Källen, 2013 Einarson, 2009 Djulus (Controls unexposed, disease free), 2006 8 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.89[0.49; 1.63]1014450%NAChan (Controls exposed to SSRIs), 2024 Winterfeld (Controls exposed to SSRI), 2015 Djulus (Controls exposed to other antidepressants), 2006 30.510.01.0