Tricyclic antidepressants updated on 07-01-2025

Early intrauterine deaths (< 22 weeks) / Spontaneous abortions

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.
S12960
R49169		 Kitchin, 2022 Miscarriage (pregnancy losses between 4-22 weeks) 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.36 [0.86;2.15] 28/84   18,042/72,195 18,070 84
ref
S11594
R42482		 Ozturk - Amitriptyline, 2016 Miscarriages at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.26 [0.11;45.78] C 0/4   15/261 15 4
ref
S11228
R41309		 Abadie, 2015 Spontaneous abortion (before the 22nd week of amenorrhea) 1st trimester nested case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.19 [1.46;3.29] 39/127   799/5,219 838 127
ref
S11196
R41255		 Kjaersgaard (Controls unexposed, NOS), 2013 Spontaneous abortion (before 22 weeks of gestation) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.47 [1.28;1.70]
excluded (control group) 		-/-   -/983,258 - -
ref
S11200
R41256		 Kjaersgaard (Controls unexposed, sick), 2013 Spontaneous abortion (before 22 weeks of gestation) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.04 [0.60;1.78] -/-   -/- - -
ref
S11223
R41298		 Ban (Controls exposed to SSRIs), 2012 Miscarriage (NOS) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: TCA only 1.03 [0.94;1.13] C
excluded (control group) 		650/4,349   2,069/14,191 2,719 4,349
ref
S11221
R41291		 Ban (Controls unexposed, disease free), 2012 Miscarriage (NOS) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes Monotherapy: TCA only 1.30 [1.10;1.50]
excluded (control group) 		650/4,349   -/- - 4,349
ref
S11222
R41295		 Ban (Controls unexposed, sick), 2012 Miscarriage (NOS) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: TCA only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.30 [1.10;1.50] 650/4,349   -/- - 4,349
ref
S11121
R41090		 Nakhai-Pour, 2010 Spontaneous abortions (< 20th week of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: TCA only 1.27 [0.85;1.91] 36/-   5,088/- 5,124 -
ref
S11262
R41392		 Yaris, 2005 Spontaneous abortions during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.53 [0.07;4.29] C 1/51   9/248 10 51
ref
S10931
R40650		 Pastuszak (Controls exposed to Fluoxetine), 1993 Spontaneous abortion (NOS) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: TCA only 0.89 [0.34;2.32] C
excluded (control group) 		9/74   10/74 19 74
ref
S10932
R40661		 Pastuszak (Controls unexposed, NOS), 1993 Spontaneous abortion (NOS) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: TCA only 1.91 [0.61;6.00] C 9/74   5/74 14 74
ref
Total 8 studies 1.38 [1.17;1.62] 24,071 4,689
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 Kitchin, 2022Kitchin, 2022 1.36[0.86; 2.15]18,0708411%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Ozturk - Amitriptyline, 2016Ozturk - Amitriptyline, 2016 2.26[0.11; 45.78]1540%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Abadie, 2015Abadie, 2015 2.19[1.46; 3.29]83812713%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: critical Kjaersgaard (Controls unexposed, sick), 2013Kjaersgaard, 2013 1 1.04[0.60; 1.78]--8%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Ban (Controls unexposed, sick), 2012Ban, 2012 2 1.30[1.10; 1.50]-4,34951%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Nakhai-Pour, 2010Nakhai-Pour, 2010 1.27[0.85; 1.91]5,124-14%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Yaris, 2005Yaris, 2005 0.53[0.07; 4.29]10511%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Pastuszak (Controls unexposed, NOS), 1993Pastuszak, 1993 3 1.91[0.61; 6.00]14742%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (8 studies) I2 = 11% 1.38[1.17; 1.62]24,0714,6890.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.28[1.11; 1.49]394,4780%NAOzturk - Amitriptyline, 2016 Kjaersgaard (Controls unexposed, sick), 2013 Ban (Controls unexposed, sick), 2012 Yaris, 2005 Pastuszak (Controls unexposed, NOS), 1993 5 case control studiescase control studies 1.57[1.11; 2.21]24,03221150%NAKitchin, 2022 Abadie, 2015 Nakhai-Pour, 2010 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.57[1.22; 2.00]24,0713404%NAKitchin, 2022 Ozturk - Amitriptyline, 2016 Abadie, 2015 Nakhai-Pour, 2010 Yaris, 2005 Pastuszak (Controls unexposed, NOS), 1993 6 unexposed, sickunexposed, sick 1.28[1.10; 1.48]-4,3490%NAKjaersgaard (Controls unexposed, sick), 2013 Ban (Controls unexposed, sick), 2012 2 Tags Adjustment   - No  - No 1.14[0.71; 1.82]391290%NAOzturk - Amitriptyline, 2016 Kjaersgaard (Controls unexposed, sick), 2013 Yaris, 2005 Pastuszak (Controls unexposed, NOS), 1993 4   - Yes  - Yes 1.45[1.15; 1.82]24,0324,56047%NAKitchin, 2022 Abadie, 2015 Ban (Controls unexposed, sick), 2012 Nakhai-Pour, 2010 4 MatchedMatched 1.33[0.91; 1.95]5,138740%NANakhai-Pour, 2010 Pastuszak (Controls unexposed, NOS), 1993 2 Monotherapy   - no or not specified  - no or not specified 1.47[1.01; 2.14]18,93326636%NAKitchin, 2022 Ozturk - Amitriptyline, 2016 Abadie, 2015 Kjaersgaard (Controls unexposed, sick), 2013 Yaris, 2005 5   - TCA only  - TCA only 1.30[1.13; 1.51]5,1384,4230%NABan (Controls unexposed, sick), 2012 Nakhai-Pour, 2010 Pastuszak (Controls unexposed, NOS), 1993 3 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.04[0.60; 1.79]-- -NAKjaersgaard (Controls unexposed, sick), 2013 1   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.30[1.11; 1.52]-4,349 -NABan (Controls unexposed, sick), 2012 1 All studiesAll studies 1.38[1.17; 1.62]24,0714,68911%NAKitchin, 2022 Ozturk - Amitriptyline, 2016 Abadie, 2015 Kjaersgaard (Controls unexposed, sick), 2013 Ban (Controls unexposed, sick), 2012 Nakhai-Pour, 2010 Yaris, 2005 Pastuszak (Controls unexposed, NOS), 1993 80.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.91.8410.000Kitchin, 2022Ozturk - Amitriptyline, 2016Abadie, 2015Kjaersgaard (Controls unexposed, sick), 2013Ban (Controls unexposed, sick), 2012Nakhai-Pour, 2010Yaris, 2005Pastuszak (Controls unexposed, NOS), 1993

Asymetry test p-value = 0.7923 (by Egger's regression)

slope=0.2804 (0.1129); intercept=0.1710 (0.6208); t=0.2754; p=0.7923

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10931, 11223, 11221, 11196

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.42[1.28; 1.58]24,7124,7165%NAKitchin, 2022 Ozturk - Amitriptyline, 2016 Abadie, 2015 Kjaersgaard (Controls unexposed, NOS), 2013 Ban (Controls unexposed, disease free), 2012 Nakhai-Pour, 2010 Yaris, 2005 Pastuszak (Controls unexposed, NOS), 1993 8 unexposed, sick controlsunexposed, sick controls 1.28[1.10; 1.48]6414,3490%NAKjaersgaard (Controls unexposed, sick), 2013 Ban (Controls unexposed, sick), 2012 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.03[0.93; 1.13]2,7384,4230%NABan (Controls exposed to SSRIs), 2012 Pastuszak (Controls exposed to Fluoxetine), 1993 20.510.01.0