Atypical antipsychotics (Second generation) updated on 06-10-2025

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.
S18393
R77588
Chan (Controls exposed to FGA), 2024 Nervous system malformations at least 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.40 [0.08;2.06] C
excluded (control group)
2/419   5/420 7 419
ref
S18339
R77370
Chan (Controls unexposed, general pop), 2024 Nervous system malformations at least 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes 1.47 [0.15;21.60]
excluded (control group)
2/419   1,927/464,017 1,929 419
ref
S18392
R77582
Chan (Controls unexposed, sick), 2024 Nervous system malformations at least 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 2.92 [0.22;204.05] 2/363   48/6,476 50 363
ref
S12148
R44997
Ellfolk (Controls exposed to FGA), 2021 Central nervous system malformations (ICD-9; 740–742) 1st trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes 0.53 [0.12;2.29]
excluded (control group)
8/3,478   7/1,030 15 3,478
ref
S12146
R44977
Ellfolk (Controls unexposed, NOS), 2021 Central nervous system malformations (ICD-9; 740–742) 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Matched 0.44 [0.13;1.53] 8/3,478   47/22,540 55 3,478
ref
S2341
R2754
Habermann (Control exposed to FGA), 2013 Malformations Nervous system 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 2.49 [0.12;52.00] C
excluded (control group)
2/430   0/213 2 430
ref
S2385
R2932
Habermann (Control unexposed, disease free), 2013 Malformations Nervous system 1st trimester prospective cohort unexposed, disease free Adjustment: No 4.73 [0.43;52.34] C 2/430   1/1,014 3 430
ref
Total 3 studies 1.24 [0.23;6.68] 108 4,271
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, sick), 2024Chan, 2024 1 2.92[0.22; 204.05]5036318%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Ellfolk (Controls unexposed, NOS), 2021Ellfolk, 2021 2 0.44[0.13; 1.53]553,47853%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Habermann (Control unexposed, disease free), 2013Habermann, 2013 3 4.73[0.43; 52.34]343029%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: low Total (3 studies) I2 = 44% 1.24[0.23; 6.68]1084,2710.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, NOS; 3: Control unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.24[0.23; 6.68]1084,27144%NAChan (Controls unexposed, sick), 2024 Ellfolk (Controls unexposed, NOS), 2021 Habermann (Control unexposed, disease free), 2013 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.14[0.12; 11.21]583,90866%NAEllfolk (Controls unexposed, NOS), 2021 Habermann (Control unexposed, disease free), 2013 2 unexposed, sickunexposed, sick 2.92[0.10; 88.93]50363 -NAChan (Controls unexposed, sick), 2024 1 Tags Adjustment   - No  - No 4.73[0.43; 52.34]3430 -NAHabermann (Control unexposed, disease free), 2013 1   - Yes  - Yes 0.56[0.16; 1.97]1053,8414%NAChan (Controls unexposed, sick), 2024 Ellfolk (Controls unexposed, NOS), 2021 2 MatchedMatched 0.44[0.13; 1.51]553,478 -NAEllfolk (Controls unexposed, NOS), 2021 1 All studiesAll studies 1.24[0.23; 6.68]1084,27144%NAChan (Controls unexposed, sick), 2024 Ellfolk (Controls unexposed, NOS), 2021 Habermann (Control unexposed, disease free), 2013 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 2341, 12148, 18393, 18339

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.06[0.25; 4.43]1,9874,32738%NAChan (Controls unexposed, general pop), 2024 Ellfolk (Controls unexposed, NOS), 2021 Habermann (Control unexposed, disease free), 2013 3 unexposed, sick controlsunexposed, sick controls 2.92[0.10; 88.93]50363 -NAChan (Controls unexposed, sick), 2024 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.57[0.20; 1.59]244,3270%NAChan (Controls exposed to FGA), 2024 Ellfolk (Controls exposed to FGA), 2021 Habermann (Control exposed to FGA), 2013 30.510.01.0