Sex Differences in Diagnosis and Treatment Timing of Comorbid Depression/Anxiety and Disease Subtypes in Patients With ADHD: A Database Study

Abstract

Objective:

Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD.

Method:

To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences.

Results:

Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients.

Conclusions:

Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment.

Keywords

anxiety attention deficit disorder with hyperactivity depression female gender differences humans male real world evidence real world data sex factors

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References

Arnett

A. B.

Pennington

B. F.

Willcutt

E. G.

DeFries

J. C.

Olson

R. K.

(2015). Sex differences in ADHD symptom severity. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 56(6), 632–639. https://doi.org/10.1111/jcpp.12337

Austin

P. C.

(2009). Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Statistics in Medicine, 28(25), 3083-3107. https://doi.org/10.1002/sim.3697

Babinski

D. E.

Neely

K. A.

D. M.

Liu

(2020). Depression and suicidal behavior in young adult men and women with ADHD: Evidence from claims data. Journal of Clinical Psychiatry, 81(6), 19m13130. https://doi.org/10.4088/JCP.19m13130

Babinski

D. E.

Waschbusch

D. A.

Waxmonsky

J. G.

(2019). Sex and pubertal status moderate the association between ADHD and depression symptoms: An examination from preadolescence through late adolescence. Journal of Clinical Psychiatry, 80(3), 18m12548. https://doi.org/10.4088/JCP.18m12548

Babinski

Shroff

D. M.

Cao

V. T.

Waschbusch

D. A.

(2021). Sex-specific norms for diagnosing attention-deficit/hyperactivity disorder in childhood: A receiver operating characteristic (ROC) analysis. Evidence-Based Practice in Child and Adolescent Mental Health, 6(2), 290-302. https://doi.org/10.1080/23794925.2021.1875343

Bruchmüller

Margraf

Schneider

(2012). Is ADHD diagnosed in accord with diagnostic criteria? Overdiagnosis and influence of client gender on diagnosis. Journal of Consulting and Clinical Psychology, 80(1), 128-138. https://doi.org/10.1037/a0026582

Carucci

Narducci

Bazzoni

Balia

Donno

Gagliano

Zuddas

(2022). Clinical characteristics, neuroimaging findings, and neuropsychological functioning in attention-deficit hyperactivity disorder: Sex differences. Journal of Neuroscience Research, 101(5), 704-717. https://doi.org/10.1002/jnr.25038

Centers for Disease Control and Prevention. (2022). What is ADHD? https://www.cdc.gov/ncbddd/adhd/facts.html

Childress

A. C.

Newcorn

J. H.

Cutler

A. J.

(2019). Gender effects in the efficacy of racemic amphetamine sulfate in children with attention-deficit/hyperactivity disorder. Advances in Therapy, 36(6), 1370-1387. https://doi.org/10.1007/s12325-019-00942-5

10.

Coxe

Sibley

M. H.

Becker

S. P.

(2021). Presenting problem profiles for adolescents with ADHD: Differences by sex, age, race, and family adversity. Child and Adolescent Mental Health, 26(3), 228-237. doi:10.1111/camh.12441

11.

D’Agati

Curatolo

Mazzone

(2019). Comorbidity between ADHD and anxiety disorders across the lifespan. International Journal of Psychiatry Clinical Practice, 23(4), 238-244. https://doi.org/10.1080/13651501.2019.1628277

12.

Danielson

M. L.

Bitsko

R. H.

Ghandour

R. M.

Holbrook

J. R.

Kogan

M. D.

Blumberg

S. J.

(2018). Prevalence of parent-reported ADHD diagnosis and associated treatment among U.S. children and adolescents, 2016. Journal of Clinical Child and Adolescent Psychology, 47(2), 199-212. https://doi.org/10.1080/15374416.2017.1417860

13.

De Ronda

A. C.

Rice

Zhao

Rosch

K. S.

Mostofsky

S. H.

Seymour

K. E

. (2023). ADHD-related sex differences in emotional symptoms across development. European Child & Adolescent Psychiatry. Advance online publication. https://doi.org/10.1007/s00787-023-02251-3

14.

De Rossi

Pretelli

Menghini

D’Aiello

Di Vara

Vicari

. (2022). Gender-related clinical characteristics in children and adolescents with ADHD. Journal of Clinical Medicine, 11(2), 385. https://doi.org/10.3390/jcm11020385

15.

Faraone

S. V.

Banaschewski

Coghill

Zheng

Biederman

Bellgrove

M. A.

Newcorn

J. H.

Wang

(2021). The World Federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder. Neuroscience and Biobehavioral Reviews, 128, 789-818. https://doi.org/10.1016/j.neubiorev.2021.01.022

16.

Fraticelli

Caratelli

De Berardis

Ducci

Pettorruso

Martinotti

Di Cesare

di Giannantonio

(2022). Gender differences in attention deficit hyperactivity disorder: An update of the current evidence. Rivista di psichiatria, 57(4), 159-164. https://doi.org/10.1708/3855.38380.

17.

Hasson

Fine

J. G.

(2012). Gender differences among children with ADHD on continuous performance tests: A meta-analytic review. Journal of Attention Disorders, 16(3), 190-198. https://doi.org/10.1177/1087054711427398

18.

Hinshaw

S. P.

Nguyen

P. T.

O’Grady

S. M.

Rosenthal

E. A.

(2022). Annual research review: Attention-deficit/hyperactivity disorder in girls and women: Underrepresentation, longitudinal processes, and key directions. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 63(4), 484-496. https://doi.org/10.1111/jcpp.13480

19.

Hripcsak

Duke

J. D.

Shah

N. H.

Reich

C. G.

Huser

Schuemie

M. J.

Suchard

M. A.

Ryan

P. B.

(2015). Observational Health Data Sciences and Informatics (OHDSI): Opportunities for observational researchers. Studies in Health Technology and Informatics, 216, 574-578.

20.

International Classification of Diseases for Mortality and Morbidity Statistics, 11th revision. (2022). 6A05 attention deficit hyperactivity disorder. World Health Organization. https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficdlk%2fentity%2f821852937.

21.

IpÇi

Izmir

S. B. I.

TÜrkÇapar

M. H.

Özdel

ArdiÇ

Ü. A.

Ercan

E. S.

(2020). Psychiatric comorbidity in the subtypes of ADHD in children and adolescents with ADHD according to DSM-IV. Archives Neuropsychiatry, 57(4), 283-289. https://doi.org/10.29399/npa.24807

22.

Janiczak

Perez-Reisler

Ballard

(2020). Diagnosis and management of comorbid anxiety and ADHD in pediatric primary care. Pediatric Annals, 49(10), e436-e439. https://doi.org/10.3928/19382359-20200922-01.

23.

Janssen CDM Documentation. (2021). GitHub IO. https://ohdsi.github.io/ETL-LambdaBuilder/

24.

Klefsjö

Kantzer

A. K.

Gillberg

Billstedt

(2021). The road to diagnosis and treatment in girls and boys with ADHD - gender differences in the diagnostic process. Nordic Journal of Psychiatry, 75(4), 301-305. https://doi.org/10.1080/08039488.2020.1850859

25.

Koyuncu

Ayan

Ince Guliyev

Erbilgin

Deveci

(2022). ADHD and anxiety disorder comorbidity in children and adults: Diagnostic and therapeutic challenges. Current Psychiatry Reports, 24(2), 129-140. https://doi.org/10.1007/s11920-022-01324-5

26.

Lau

T. W. I.

Lim

C. G.

Acharryya

Lim-Ashworth

Tan

Y. R.

Fung

S. S. D.

(2021). Gender differences in externalizing and internalizing problems in Singaporean children and adolescents with attention-deficit/hyperactivity disorder. Child and Adolescent Psychiatry and Mental Health, 15(1), 3. https://doi.org/10.1186/s13034-021-00356-8

27.

Loyer Carbonneau

Demers

Bigras

Guay

M. C

. (2021). Meta-analysis of sex differences in ADHD symptoms and associated cognitive deficits. Journal of Attention Disorders, 25(12), 1640-1656. https://doi.org/10.1177/1087054720923736

28.

Millenet

Laucht

Hohm

Jennen-Steinmetz

Hohmann

Schmidt

M. H.

Esser

Zohsel

(2018). Sex-specific trajectories of ADHD symptoms from adolescence to young adulthood. European Child & Adolescent Psychiatry, 27(8), 1067-1075. https://doi.org/10.1007/s00787-018-1129-9

29.

Mowlem

Agnew-Blais

Taylor

Asherson

(2019). Do different factors influence whether girls versus boys meet ADHD diagnostic criteria? Sex differences among children with high ADHD symptoms. Psychiatry Research, 272, 765-773. https://doi.org/10.1016/j.psychres.2018.12.128

30.

Mowlem

F. D.

Rosenqvist

M. A.

Martin

Lichtenstein

Asherson

Larsson

(2019). Sex differences in predicting ADHD clinical diagnosis and pharmacological treatment. European Child & Adolescent Psychiatry, 28(4), 481-489. https://doi.org/10.1007/s00787-018-1211-3

31.

Murray

A. L.

Booth

Eisner

Auyeung

Murray

Ribeaud

(2019). Sex differences in ADHD trajectories across childhood and adolescence. Developmental Science, 22(1), e12721. https://doi.org/10.1111/desc.12721

32.

Norén Selinus

Molero

Lichtenstein

Anckarsäter

Lundström

Bottai

Hellner Gumpert

. (2016). Subthreshold and threshold attention deficit hyperactivity disorder symptoms in childhood: Psychosocial outcomes in adolescence in boys and girls. Acta Psychiatrica Scandinavica, 134(6), 533-545. https://doi.org/10.1111/acps.12655

33.

Nøvik

T. S.

Hervas

Ralston

S. J.

Dalsgaard

Rodrigues Pereira

Lorenzo

M. J.

& ADORE Study Group. (2006). Influence of gender on attention-deficit/hyperactivity disorder in Europe - ADORE. European Child & Adolescent Psychiatry, 15(1), I15-I24. https://doi.org/10.1007/s00787-006-1003-z

34.

Observational Health Data Sciences and Informatics. (2021). The book of OHDSI. https://ohdsi.github.io/TheBookOfOhdsi/

35.

Overhage

J. M.

Ryan

P. B.

Reich

C. G.

Hartzema

A. G.

Stang

P. E.

(2012). Validation of a common data model for active safety surveillance research. Journal of the American Medical Informatics Association, 19(1), 54-60. https://doi.org/10.1136/amiajnl-2011-000376

36.

Quenneville

A. F.

Kalogeropoulou

Nicastro

Weibel

Chanut

Perroud

(2022). Anxiety disorders in adult ADHD: A frequent comorbidity and a risk factor for externalizing problems. Psychiatry Research, 310, 114423. https://doi.org/10.1016/j.psychres.2022.114423

37.

Quinn

P. O.

Madhoo

(2014). A review of attention-deficit/hyperactivity disorder in women and girls: Uncovering this hidden diagnosis. Prim Care Companion CNS Disorders, 16(3), PCC.13r01596. https://doi.org/10.4088/PCC.13r01596

38.

Reich

Ostropolets

Ryan

Rijnbeek

Schuemie

Davydov

Dymshyts

Hripcsak

(2024). OHDSI Standardized Vocabularies-a large-scale centralized reference ontology for international data harmonization. Journal of the American Medical Informatics Association: JAMIA, 31(3), 583–590. https://doi.org/10.1093/jamia/ocad247

39.

Robison

R. J.

Reimherr

F. W.

Marchant

B. K.

Faraone

S. V.

Adler

L. A.

West

S. A.

(2008). Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: A retrospective data analysis. Journal of Clinical Psychiatry, 69(2), 213-221. https://doi.org/10.4088/jcp.v69n0207

40.

Skogli

E. W.

Teicher

M. H.

Andersen

P. N.

Hovik

K. T.

Øie

(2013). ADHD in girls and boys: Gender differences in co-existing symptoms and executive function measures. BMC Psychiatry, 13, 298. https://doi.org/10.1186/1471-244X-13-298

41.

Soendergaard

H. M.

Thomsen

P. H.

Pedersen

Poulsen

A. E.

Winther

Nielsen

J. M.

Henriksen

Rungoe

Soegaard

H. J.

(2016). Associations of age, gender, and subtypes with ADHD symptoms and related comorbidity in a Danish sample of clinically referred adults. Journal of Attention Disorders, 20(11), 925-933. https://doi.org/10.1177/1087054713517544

42.

Sonuga-Barke

E. J. S.

Coghill

Markowitz

J. S.

Swanson

J. M.

Vandenberghe

Hatch

S. J.

(2007). Sex differences in the response of children with ADHD to once-daily formulations of methylphenidate. Journal of the American Academy of Child and Adolescent Psychiatry, 46(6), 701-710. https://doi.org/10.1097/chi.0b013e31804659f1

43.

Thorell

L. B.

Rydell

A. M.

(2008). Behaviour problems and social competence deficits associated with symptoms of attention-deficit/hyperactivity disorder: Effects of age and gender. Child: Care, Health and Development, 34(5), 584-595. https://doi.org/10.1111/j.1365-2214.2008.00869.x

44.

Valo

Tannock

(2010) Diagnostic instability of DSM-IV ADHD subtypes: Effects of informant source, instrumentation, and methods for combining symptom reports. Journal of Clinical Child and Adolescent Psychology, 39(6), 749-760. https://doi.org/10.1080/15374416.2010.517172

45.

Voss

E. A.

Makadia

Matcho

Knoll

Schuemie

DeFalco

F. J.

Londhe

Zhu.

Ryan

P. B.

(2015). Feasibility and utility of applications of the common data model to multiple, disparate observational health databases. Journal of the American Medical Informatics Association, 22(3), 553-564. doi:10.1093/jamia/ocu023

46.

Waschbusch

D. A.

King

(2006). Should sex-specific norms be used to assess attention-deficit/hyperactivity disorder or oppositional defiant disorder? Journal of Consulting and Clinical Psychology, 74(1), 179-185. https://doi.org/10.1037/0022-006X.74.1.179

47.

Williamson

Johnston

(2015). Gender differences in adults with attention-deficit/hyperactivity disorder: A narrative review. Clinical Psychology Review, 40, 15-27. https://doi.org/10.1016/j.cpr.2015.05.005

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