Fluoxetine updated on 07-01-2025

Limb defects

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.
S7469
R22232		 Anderson, 2020 Any limb deficiency 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.79 [1.01;3.18] -/-   0/- - -
ref
S7438
R21946		 Bérard, 2017 Musculoskeletal system 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.99 [0.48;2.01] -/191   -/14,847 - 191
ref
S5882
R14691		 Ban (Controls unexposed, disease free), 2014 Limb malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.89 [0.52;1.50]
excluded (control group) 		-/3,189   1,750/325,294 - 3,189
ref
S5883
R14712		 Ban (Controls unexposed, sick), 2014 Limb malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.83 [0.47;1.49] -/3,189   71/13,432 - 3,189
ref
S10218
R37437		 De Jonge, 2013 Limb malformations 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.21 [0.07;19.67] C 0/65   184/29,342 184 65
ref
S6016
R15535		 Jimenez-Solem (Controls unexposed, NOS), 2012 Congenital malformations of the limbs 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.76 [0.41;1.42]
excluded (control group) 		10/928   11,785/843,797 11,795 928
ref
S6021
R15616		 Jimenez-Solem (Controls unexposed, sick), 2012 Congenital malformations of the limbs 1st trimester population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.62 [0.27;1.40] C 10/928   14/806 24 928
ref
S7194
R20426		 Colvin, 2011 Musculoskeletal defects (ICD 754–756) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.93 [0.30;2.89] -/291   1,052/94,561 - 291
ref
S6242
R16500		 Malm, 2011 Musculoskeletal malformations (including limb defects) 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.69 [0.40;1.12] -/1,818   -/628,607 - 1,818
ref
Total 7 studies 0.93 [0.69;1.27] 208 6,482
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 Anderson, 2020Anderson, 2020 1.79[1.01; 3.18]--21%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard, 2017Bérard, 2017 0.99[0.48; 2.01]-19115%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 0.83[0.47; 1.49]-3,18921%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate De Jonge, 2013De Jonge, 2013 1.21[0.07; 19.67]184651%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 2 0.62[0.27; 1.40]2492812%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.93[0.30; 2.89]-2917%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 0.69[0.40; 1.12]-1,81824%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (7 studies) I2 = 20% 0.93[0.69; 1.27]2086,4820.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.78[0.58; 1.05]246,4170%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 5 case control studiescase control studies 1.76[1.00; 3.09]184650%NAAnderson, 2020 De Jonge, 2013 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.07[0.59; 1.94]1842,17449%NAAnderson, 2020 De Jonge, 2013 Colvin, 2011 Malm, 2011 4 unexposed, sickunexposed, sick 0.82[0.55; 1.21]244,3080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 0.73[0.38; 1.39]2081,2840%NADe Jonge, 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 3   - Yes  - Yes 1.00[0.65; 1.53]-5,19853%NAAnderson, 2020 Bérard, 2017 Ban (Controls unexposed, sick), 2014 Malm, 2011 4 Monotherapy   - no or not specified  - no or not specified 0.70[0.42; 1.17]1841,8830%NADe Jonge, 2013 Malm, 2011 2   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.39[0.78; 2.46]-19138%NAAnderson, 2020 Bérard, 2017 2   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.78[0.50; 1.20]244,4080%NABan (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 3 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.82[0.55; 1.21]244,3080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 All studiesAll studies 0.93[0.69; 1.27]2086,48220%NAAnderson, 2020 Bérard, 2017 Ban (Controls unexposed, sick), 2014 De Jonge, 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.31.7060.000Anderson, 2020Bérard, 2017Ban (Controls unexposed, sick), 2014De Jonge, 2013Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Malm, 2011

Asymetry test p-value = 0.9966 (by Egger's regression)

slope=-0.0701 (0.4569); intercept=0.0058 (1.2742); t=0.0045; p=0.9966

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6016, 5882

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.95[0.68; 1.32]14,7636,29126%NAAnderson, 2020 Ban (Controls unexposed, disease free), 2014 De Jonge, 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 6 unexposed, sick controlsunexposed, sick controls 0.82[0.55; 1.21]864,3080%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao (Musculoskeletal system anomalies)Gao (Musculoskeletal system anomalies) 0.82[0.54; 1.22]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT4 metaPregmetaPreg 0.93[0.69; 1.27]20%6,482----Anderson, 2020 Bérard, 2017 Ban (Controls unexposed, sick), 2014 De Jonge, 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 70.510.01.0