Citalopram updated on 07-01-2025

ASD (Autism spectrum disorder): Diagnosis

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.
S18376
R77459		 Heuvelman, 2023 Autism spectrum disorder - Validated Read code list among primary care clinical and referral records - Mean age at end of follow-up 10.04 years, range 4–22 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.57 [1.17;2.11] -/4,620   -/16,330 - 4,620
ref
S18255
R76624		 Suarez (Controls unexposed, discontinuers), 2022 Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year of age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.28 [0.83;1.97] 92/13,797   42/7,605 134 13,797
ref
S18256
R76632		 Suarez (Controls unexposed, general pop), 2022 Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year of age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.13 [0.90;1.41]
excluded (control group) 		92/13,818   11,199/2,920,559 11,291 13,818
ref
S10005
R35961		 Ames, 2021 Autism spectrum disorder (ASD): diagnostic criteria on the Autism Diagnostic Observation Schedule and the full ASD diagnostic criteria on the ADI-R or one of three alternative criteria on the ADI-R (age NOS). 3 months (or more) before pregnancy or during pregnancy excluded case control unexposed, disease free Adjustment: No Monotherapy: no or not specified 1.31 [0.64;2.65] C
excluded (exposition period) 		16/31   1,351/3,007 1,367 31
ref
S6547
R18028		 Brown, 2017 Autism spectrum disorder (ASD) Diagnostic (ICD-9/OHIP: 299; ICD-10: F84) - Age: 4-10 years (mean: 4.95 years) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.46 [0.50;4.25] -/-   -/- - -
ref
S11338
R41746		 Rai (Controls exposed to TCA), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) - At 4-17 years during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: no or not specified 0.70 [0.39;1.25] C
excluded (control group) 		52/1,064   16/235 68 1,064
ref
S7482
R22398		 Rai (Controls unexposed, disease free), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) at 4-17 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: no or not specified 2.46 [1.86;3.26] C
excluded (control group) 		52/1,064   4,889/238,943 4,941 1,064
ref
S7826
R23237		 Rai (Controls unexposed, sick), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) at 4-17 years during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.65 [1.20;2.26] 52/1,064   353/12,325 405 1,064
ref
S7637
R22601		 Viktorin (citalopram or escitalopram) (Controls unexposed, NOS), 2017 Autism spectrum disorder (ICD10- F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9) at 7-8 years during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.71 [1.16;2.51]
excluded (control group) 		28/1,097   1,524/172,646 1,552 1,097
ref
S7820
R23228		 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 Autism spectrum disorder (ICD10- F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9) at 7-8 years during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.47 [0.92;2.35] 19/639   -/- - 639
ref
S7859
R23782		 Bérard, 2016 Autism spectrum disorder (ICD-9 codes 299.0, 299.8, 299.9; ICD-10 codes F84.0, F84.1, F84.5, F84.8, F84.9) - Age : 0-11 years (mean: 4.0) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 2.23 [1.01;4.92] 5/421   1,004/142,716 1,009 421
ref
Total 6 studies 1.55 [1.31;1.84] 1,548 20,541
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 Heuvelman, 2023Heuvelman, 2023 1.57[1.17; 2.11]-4,62034%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: low Suarez (Controls unexposed, discontinuers), 2022Suarez, 2022 1 1.28[0.83; 1.97]13413,79716%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Brown, 2017Brown, 2017 1.46[0.50; 4.25]--3%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Rai (Controls unexposed, sick), 2017Rai, 2017 2 1.65[1.20; 2.26]4051,06429%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017Viktorin, 2017 3 1.47[0.92; 2.35]-63913%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard, 2016Bérard, 2016 2.23[1.01; 4.92]1,0094215%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 1.55[1.31; 1.84]1,54820,5410.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, discontinuers; 2: Controls unexposed, sick; 3: citalopram or escitalopram) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.55[1.31; 1.84]1,54820,5410%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 Bérard, 2016 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.92[1.02; 3.63]1,0094210%NABrown, 2017 Bérard, 2016 2 unexposed, sickunexposed, sick 1.53[1.28; 1.82]53920,1200%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 4 Tags Adjustment   - Yes  - Yes 1.55[1.31; 1.84]1,54820,5410%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 Bérard, 2016 6 Monotherapy   - no or not specified  - no or not specified 1.52[1.28; 1.82]53920,1200%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 5   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 2.23[1.01; 4.92]1,009421 -NABérard, 2016 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.57[1.17; 2.11]-4,620 -NAHeuvelman, 2023 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.59[1.22; 2.07]4051,7030%NARai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 2   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.28[0.83; 1.97]13413,797 -NASuarez (Controls unexposed, discontinuers), 2022 1 All studiesAll studies 1.55[1.31; 1.84]1,54820,5410%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 Bérard, 2016 60.55.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.31.70.6550.000Heuvelman, 2023Suarez (Controls unexposed, discontinuers), 2022Brown, 2017Rai (Controls unexposed, sick), 2017Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017Bérard, 2016

Asymetry test p-value = 0.8213 (by Egger's regression)

slope=0.4049 (0.1537); intercept=0.1726 (0.7158); t=0.2411; p=0.8213

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 11338, 7482, 7637, 18256

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.72[1.14; 2.57]18,79316,40079%NASuarez (Controls unexposed, general pop), 2022 Brown, 2017 Rai (Controls unexposed, disease free), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, NOS), 2017 Bérard, 2016 5 unexposed, sick controlsunexposed, sick controls 1.53[1.28; 1.82]54920,1200%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.70[0.39; 1.25]681,064 -NARai (Controls exposed to TCA), 2017 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Halvorsen - Citalopram/escitalopram (Autism s ...Halvorsen - Citalopram/escitalopram (Autism spectrum disorder _ Cohort studies) 1.68[1.17; 2.42]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 1.55[1.31; 1.84]0%20,541----Heuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (citalopram or escitalopram) (Controls unexposed, sick), 2017 Bérard, 2016 60.510.01.0