Fluoxetine updated on 07-01-2025

Nervous system anomalies

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.
S7438
R21939		 Bérard, 2017 Nervous system malformations 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) 0.64 [0.09;4.52] -/191   -/14,847 - 191
ref
S5882
R14696		 Ban (Controls unexposed, disease free), 2014 Nervous system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.77 [0.87;3.57] -/3,189   465/325,294 - 3,189
ref
S6016
R15536		 Jimenez-Solem (Controls unexposed, NOS), 2012 Malformations of the nervous system 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.44 [0.36;5.79] 2/928   -/843,797 - 928
ref
S7194
R20419		 Colvin, 2011 Nervous system defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.56 [0.03;9.00] C 0/291   289/94,561 289 291
ref
S6242
R16493		 Malm, 2011 Central nervous system 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.95 [0.42;2.15] -/1,818   -/628,607 - 1,818
ref
Total 5 studies 1.27 [0.79;2.05] 289 6,417
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 Bérard, 2017Bérard, 2017 0.64[0.09; 4.52]-1916%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, disease free), 2014Ban, 2014 1 1.77[0.87; 3.57]-3,18945%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 2 1.44[0.36; 5.79]-92812%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.56[0.03; 9.00]2892913%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 0.95[0.42; 2.15]-1,81834%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 0% 1.27[0.79; 2.05]2896,4170.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, disease free; 2: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.27[0.79; 2.05]2896,4170%NABérard, 2017 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.33[0.81; 2.17]2896,2260%NABan (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 4 unexposed, sickunexposed, sick 0.64[0.09; 4.54]-191 -NABérard, 2017 1 Tags Adjustment   - No  - No 0.56[0.03; 9.00]289291 -NAColvin, 2011 1   - Yes  - Yes 1.31[0.81; 2.12]-6,1260%NABérard, 2017 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 4 Monotherapy   - no or not specified  - no or not specified 0.95[0.42; 2.15]-1,818 -NAMalm, 2011 1   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.64[0.09; 4.54]-191 -NABérard, 2017 1   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.61[0.87; 2.97]2894,4080%NABan (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 3 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.64[0.09; 4.54]-191 -NABérard, 2017 1 All studiesAll studies 1.27[0.79; 2.05]2896,4170%NABérard, 2017 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.61.7000.000Bérard, 2017Ban (Controls unexposed, disease free), 2014Jimenez-Solem (Controls unexposed, NOS), 2012Colvin, 2011Malm, 2011

Asymetry test p-value = 0.2684 (by Egger's regression)

slope=0.6985 (0.3744); intercept=-0.9345 (0.6896); t=1.3552; p=0.2684

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.33[0.81; 2.17]7456,2260%NABan (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 4 unexposed, sick controlsunexposed, sick controls 0.64[0.09; 4.54]-191 -NABérard, 2017 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao (Nervous system malformations)Gao (Nervous system malformations) 1.37[0.83; 2.25]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT3 metaPregmetaPreg 1.27[0.79; 2.05]0%6,417----Bérard, 2017 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 50.510.01.0