Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Medications for attention deficit hyperactivity disorder associated with increased risk of developing glaucoma

Eye (2024)Cite this article

Subjects

Abstract

Background

Attention deficit hyperactivity disorder (ADHD) therapies including atomoxetine, methylphenidate, and amphetamines are some of the most prescribed medications in North America. Due to their sympathomimetic action, these drugs are contraindicated in patients with a history of angle closure glaucoma (ACG). This study aims to determine the risk of ACG and open angle glaucoma (OAG) among users of these treatments.

Methods

This is a retrospective cohort study with a case control analysis using the PharMetrics Plus Database (IQVIA, USA). We created a cohort of new users of atomoxetine, methylphenidate, and amphetamines and they were followed to the first diagnosis of (1) ACG or OAG; or (2) end of follow up. For each case, four age-matched controls were selected. A conditional logistic regression model was used to adjust for confounders and to calculate adjusted incidence-rate-ratios (aIRRs).

Results

A total of 240,257 new users of the ADHD medications were identified. The mean age was 45.0 ± 19.4 years and 55% of the cohort was female. Regular users of atomoxetine and amphetamines had a higher aIRR for developing ACG compared with non-users (aIRR = 2.55 95% CI [1.20–5.43] and 2.27 95% CI [1.42–3.63], respectively); while users of methylphenidate had a higher aIRR for developing OAG (aIRR = 1.23 95% CI [1.05–1.59]).

Conclusions

Use of amphetamines and atomoxetine had a higher risk for ACG, while use of methylphenidate was associated with a higher risk for OAG. Given the prevalence of ADHD medication use (medically and recreationally), our current data on their associated risk of glaucoma have profound public health implications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

Data availability

Data can be provided upon a reasonable request. The authors can share the complete data set creation plan and the analytic code upon request; please contact Dr. Mahyar Etminan. The data sets utilized in this study are accessible with permission from IQVIA. However, there are restrictions on the availability of this data, as it was used under license for this study and is not publicly accessible.

References

  1. Ayyıldız D, Ayyıldız T. Ophthalmological findings in children and adolescents with attention deficit and hyperactivity disorder. Int Phys Med Rehabil J. 2019;4:276–9.

  2. Guvenmez O, Cubuk M, Gunes S. The effects of medication on intraocular pressure in children with attention deficit hyperactivity disorder: a prospective study. J Popul Ther Clin Pharm. 2020;27:e45–50.

    Google Scholar 

  3. Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharm Ther. 2021;23:107940.

    Google Scholar 

  4. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bradley C. The behavior of children receiving benzedrine. Am J Psychiatry. 1937;94:577–85.

    Article  Google Scholar 

  6. McCabe SE, Schulenberg JE, Wilens TE, Schepis TS, McCabe VV, Veliz PT. Prescription stimulant medical and nonmedical use among US secondary school students, 2005 to 2020. JAMA Netw Open. 2023;6:e238707–07.

    Article  PubMed  PubMed Central  Google Scholar 

  7. McCabe SE, Knight JR, Teter CJ, Wechsler H. Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey. Addiction. 2005;100:96–106.

    Article  PubMed  Google Scholar 

  8. Chen LY, Crum RM, Strain EC, Alexander GC, Kaufmann C, Mojtabai R. Prescriptions, nonmedical use, and emergency department visits involving prescription stimulants. J Clin Psychiatry. 2016;77:e297–304.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lu C-K, Kuang T-M, Chou JC-K. Methylphenidate (Ritalin)-associated cataract and glaucoma. J Chin Med Assoc. 2006;69:589–90.

    Article  CAS  PubMed  Google Scholar 

  10. Bartlik B, Harmon G, Kaplan P. Use of methylphenidate in a patient with glaucoma and attention-deficit hyperactivity disorder: a clinical dilemma. Arch Gen Psychiatry. 1997;54:188–89.

    Article  CAS  PubMed  Google Scholar 

  11. Julien RG, Vincendeau J. Fuchs heterochromy, glaucoma and sympathomimetics. Bulletin des societes d’ophtalmologie de France 1956:187-8.

  12. Karabulut M, Karabulut S, Kocatürk T, Ozkan SB. Is the treatment of attention deficit hyperactivity disorder a new cause of cataract? Open J Ophthalmol 2018;8. https://doi.org/10.4236/ojoph.2018.81004

  13. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27:699–711.

    Article  CAS  PubMed  Google Scholar 

  14. Upadhyaya HP, Desaiah D, Schuh KJ, Bymaster FP, Kallman MJ, Clarke DO, et al. A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder. Psychopharmacology. 2013;226:189–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Eadie B, Etminan M, Mikelberg FS. Risk for uveitis with oral moxifloxacin: a comparative safety study. JAMA Ophthalmol. 2015;133:81–84.

    Article  PubMed  Google Scholar 

  16. Eadie BD, Etminan M, Carleton BC, Maberley DA, Mikelberg FS. Association of repeated intravitreous bevacizumab injections with risk for glaucoma surgery. JAMA Ophthalmol. 2017;135:363–68.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hussein M, Wei W, Mastey V, Sanchez RJ, Wang D, Murdock DJ, et al. Real-world effectiveness of casirivimab and imdevimab among patients diagnosed with COVID-19 in the ambulatory setting: a retrospective cohort study using a large claims database. BMJ Open. 2022;12:e064953.

    Article  PubMed  Google Scholar 

  18. Essebag V, Genest J Jr, Suissa S, Pilote L. The nested case-control study in cardiology. Am Heart J. 2003;146:581–90.

    Article  PubMed  Google Scholar 

  19. İzci F, göde öğüten E. Methylphenidate induced increase in intraocular pressure, Dusunen Adam. J Psychiatry Neurol Sci. 2016;29. https://doi.org/10.5350/dajpn2016290413.

  20. Larrañaga-Fragoso P, Noval S, Rivero J, Boto-de-los-Bueis A. The effects of methylphenidate on refraction and anterior segment parameters in children with attention deficit hyperactivity disorder. J AAPOS. 2015;19. https://doi.org/10.1016/j.jaapos.2015.04.005

  21. Duman NS, Duman R, Sarı Gökten E, Duman R. Lens opacities in children using methylphenidate hydrochloride. Cutan Ocul Toxicol. 2017;36:362–65.

    Article  CAS  PubMed  Google Scholar 

  22. Kong N, Bao Y, Zhao H, Kang X, Tai X, Shen Y. Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy. Hum Exp Toxicol. 2020;40:71–80.

    Article  PubMed  Google Scholar 

  23. Corona JC. Role of oxidative stress and neuroinflammation in attention-deficit/hyperactivity disorder. Antioxidants. 2020;9:1039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Corona JC, Carreón-Trujillo S, González-Pérez R, Gómez-Bautista D, Vázquez-González D, Salazar-García M. Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells. Sci Rep. 2019;9:13011.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Izzotti A, Bagnis A, Saccà SC. The role of oxidative stress in glaucoma. Mutat Res. 2006;612:105–14.

    Article  CAS  PubMed  Google Scholar 

  26. de la Torre R, Farré M, Navarro M, Pacifici R, Zuccaro P, Pichini S. Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet. 2004;43:157–85.

    Article  PubMed  Google Scholar 

  27. Kelly RP, Yeo KP, Teng C-H, Smith BP, Lowe S, Soon D, et al. Hemodynamic effects of acute administration of atomoxetine and methylphenidate. J Clin Pharmacol. 2005;45:851–55.

    Article  CAS  PubMed  Google Scholar 

  28. Lowe RF. Primary creeping angle-closure glaucoma. Br J Ophthalmol. 1964;48:544–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Enoch J, Jones L, Taylor DJ, Bronze C, Kirwan JF, Jones PR, et al. How do different lighting conditions affect the vision and quality of life of people with glaucoma? A systematic review. Eye. 2020;34:138–54.

    Article  PubMed  Google Scholar 

  30. D’Alli RE. Chapter 90 - Child And Adolescent Psychopharmacology. In: Carey WB, Crocker AC, Coleman WL, et al., eds. Developmental-Behavioral Pediatrics (Fourth Edition). Philadelphia: W.B. Saunders 2009:885-910.

  31. Cui YM, Teng CH, Pan AX, Yuen E, Yeo KP, Zhou Y, et al. Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele. Br J Clin Pharmacol. 2007;64:445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Trzepacz PT, Williams DW, Feldman PD, Wrishko RE, Witcher JW, Buitelaar JK. CYP2D6 metabolizer status and atomoxetine dosing in children and adolescents with ADHD. Eur Neuropsychopharmacol. 2008;18:79–86.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the Glaucoma Research Society of Canada Project Grant.

Funding

This study was funded by the Glaucoma Research Society of Canada Project Grant.

Author information

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS, Canada

    Rami Darwich, Bonnie He & Brennan D. Eadie

  2. Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada

    Mahyar Etminan

Authors
  1. Rami Darwich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahyar Etminan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bonnie He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brennan D. Eadie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RD was responsible for designing the study, conducting the search, analysing, and interpreting results, and writing the report. BH contributed to the design of the research and provided feedback on the report. ME and BE supervised the design of the study, writing the report, extracting and analysing data, interpreting the results, and provided feedback on the report.

Corresponding author

Correspondence to Mahyar Etminan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Darwich, R., Etminan, M., He, B. et al. Medications for attention deficit hyperactivity disorder associated with increased risk of developing glaucoma. Eye (2024). https://doi.org/10.1038/s41433-024-03100-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41433-024-03100-6

Search

Advanced search

Quick links