Hostname: page-component-77c89778f8-vsgnj Total loading time: 0 Render date: 2024-07-21T22:44:20.492Z Has data issue: false hasContentIssue false

Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study

Published online by Cambridge University Press:  20 February 2023

Chungsoo Kim
Affiliation:
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
Dong Yun Lee
Affiliation:
Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea
Jimyung Park
Affiliation:
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
Su-Jin Yang
Affiliation:
Gwangju Smile Center for Crime victim support, Gwangju, South Korea
Eng Hooi Tan
Affiliation:
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Centre of Statistics in Medicines, University of Oxford, Oxford, UK
Daniel Prieto-Alhambra
Affiliation:
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Centre of Statistics in Medicines, University of Oxford, Oxford, UK Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
Yo Han Lee
Affiliation:
Department of Preventive Medicine and Public Health, Ajou University School of Medicine, Suwon, South Korea
Sangha Lee
Affiliation:
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
Seong-Ju Kim
Affiliation:
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
Jeewon Lee
Affiliation:
Department of Psychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
Rae Woong Park
Affiliation:
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea
Yunmi Shin*
Affiliation:
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
*
Author for correspondence: Yunmi Shin, E-mail: ymshin@ajou.ac.kr

Abstract

Background

Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation.

Methods

We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings.

Results

The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25–0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups.

Conclusion

The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Type
Original Article
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Those authors contributed equally as co-first author.

Those authors contributed equally as co-senior author.

This article has been updated since its original publication. A notice detailing the updates can be found here: doi.org/10.1017/S0033291723001022

References

Alexander, M. W., Patrick, A. R., Lauer, M. S., Hornbrook, M. C., Marin, M. G., Platt, R., … Schneeweiss, S. (2013). A tool for assessing the feasibility of comparative effectiveness research. Comparative Effectiveness Research, 2013(3), 1120. doi:https://doi.org/10.2147/CER.S40357Google Scholar
Altindag, A., Yanik, M., & Asoglu, M. (2005). The emergence of tics during escitalopram and sertraline treatment. International Clinical Psychopharmacology, 20(3), 177178. doi:https://doi.org/10.1097/00004850-200505000-00010CrossRefGoogle ScholarPubMed
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), 632639. doi:https://doi.org/10.1111/jcpp.12337CrossRefGoogle ScholarPubMed
Baizabal-Carvallo, J. F., & Morgan, J. C. (2022). Drug-induced tremor, clinical features, diagnostic approach and management. Journal of the Neurological Sciences, 435, 120192. doi:https://doi.org/10.1016/j.jns.2022.120192CrossRefGoogle ScholarPubMed
Biederman, J., Ball, S. W., Monuteaux, M. C., Mick, E., Spencer, T. J., McCREARY, M., … Faraone, S. V. (2008). New insights into the comorbidity between ADHD and major depression in adolescent and young adult females. Journal of the American Academy of Child and Adolescent Psychiatry, 47(4), 426434. doi:https://doi.org/10.1097/CHI.0b013e31816429d3CrossRefGoogle ScholarPubMed
Blackman, G. L., Ostrander, R., & Herman, K. C. (2005). Children with ADHD and depression: A multisource, multimethod assessment of clinical, social, and academic functioning. Journal of Attention Disorders, 8(4), 195207. doi:10.1177/1087054705278777CrossRefGoogle ScholarPubMed
Boaden, K., Tomlinson, A., Cortese, S., & Cipriani, A. (2020). Antidepressants in children and adolescents: Meta-review of efficacy, tolerability and suicidality in acute treatment. Frontiers in Psychiatry, 11, 717. doi:https://doi.org/10.3389/fpsyt.2020.00717CrossRefGoogle ScholarPubMed
Bykowsky, O., Harrisberger, F., Schmidt, A., Smieskova, R., Hauke, D. J., Egloff, L., … Borgwardt, S. (2019). Association of antidepressants with brain morphology in early stages of psychosis: An imaging genomics approach. Scientific Reports, 9(1), 8516. doi:https://doi.org/10.1038/s41598-019-44903-yCrossRefGoogle ScholarPubMed
Cabarkapa, S., King, J. A., Dowling, N., & Ng, C. H. (2019). Co-morbid obsessive-compulsive disorder and attention deficit hyperactivity disorder: Neurobiological commonalities and treatment implications. Frontiers in Psychiatry, 10, 557. doi:https://doi.org/10.3389/fpsyt.2019.00557CrossRefGoogle ScholarPubMed
Chang, K. D., Saxena, K., Howe, M., & Simeonova, D. (2010). Psychotropic medication exposure and age at onset of bipolar disorder in offspring of parents with bipolar disorder. Journal of Child and Adolescent Psychopharmacology, 20(1), 2532. doi:https://doi.org/10.1089/cap.2009.0036CrossRefGoogle ScholarPubMed
Chen, Q., Sjölander, A., Runeson, B., D'Onofrio, B. M., Lichtenstein, P., & Larsson, H. (2014). Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: Register based study. British Medical Journal, 348, g3769. doi:10.1136/bmj.g3769CrossRefGoogle ScholarPubMed
Chen, V. C., Yang, Y. H., Liao, Y. T., Kuo, T. Y., Liang, H. Y., Huang, K. Y., … Lin, T. C. (2017). The association between methylphenidate treatment and the risk for fracture among young ADHD patients: A nationwide population-based study in Taiwan. PLoS ONE, 12(3), e0173762. doi:https://doi.org/10.1371/journal.pone.0173762CrossRefGoogle ScholarPubMed
Cheung, A. H., Zuckerbrot, R. A., Jensen, P. S., Laraque, D., Stein, R. E. K., Group, G.-P. S., … Sarvet, B. (2018). Guidelines for adolescent depression in primary care (GLAD-PC): Part II. Treatment and ongoing management. Pediatrics, 141(3), e20174082. doi:10.1542/peds.2017-4082CrossRefGoogle ScholarPubMed
Demireva, E. Y., Suri, D., Morelli, E., Mahadevia, D., Chuhma, N., Teixeira, C. M., … Ansorge, M. S. (2020). 5-HT2C Receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy. Molecular Psychiatry, 25(12), 33043321. doi:https://doi.org/10.1038/s41380-018-0227-xCrossRefGoogle ScholarPubMed
Fenger-Grøn, M., Vestergaard, M., Pedersen, H. S., Frost, L., Parner, E. T., Ribe, A. R., & Davydow, D. S. (2019). Depression, antidepressants, and the risk of non-valvular atrial fibrillation: A nationwide Danish matched cohort study. European Journal of Preventive Cardiology, 26(2), 187195. doi:https://doi.org/10.1177/2047487318811184CrossRefGoogle ScholarPubMed
Fornaro, M., Anastasia, A., Valchera, A., Carano, A., Orsolini, L., Vellante, F., … De Berardis, D. (2019). The FDA “Black box” warning on antidepressant suicide risk in young adults: More harm than benefits? Frontiers in Psychiatry, 10, 294. doi:10.3389/fpsyt.2019.00294.CrossRefGoogle ScholarPubMed
Frei, K., & Truong, D. D. (2022). Medications used to treat tremors. Journal of the Neurological Sciences, 435, 120194. doi:https://doi.org/10.1016/j.jns.2022.120194CrossRefGoogle ScholarPubMed
Gadow, K. D., Sverd, J., Sprafkin, J., Nolan, E. E., & Ezor, S. N. (1995). Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. Archives of General Psychiatry, 52(6), 444455. doi:https://doi.org/10.1001/archpsyc.1995.03950180030005CrossRefGoogle ScholarPubMed
Goldsmith, M., Singh, M., & Chang, K. (2011). Antidepressants and psychostimulants in pediatric populations: Is there an association with mania? Paediatric Drugs, 13(4), 225243. doi:10.2165/11591660-000000000-00000CrossRefGoogle ScholarPubMed
Ishii, M., Tatsuzawa, Y., Yoshino, A., & Nomura, S. (2008). Serotonin syndrome induced by augmentation of SSRI with methylphenidate. Psychiatry and Clinical Neurosciences, 62(2), 246246. doi:https://doi.org/10.1111/j.1440-1819.2008.01767.xCrossRefGoogle ScholarPubMed
Jick, H., Kaye, J. A., & Jick, S. S. (2004). Antidepressants and the risk of suicidal behaviors. Journal of the American Medical Association, 292(3), 338343. doi:10.1001/jama.292.3.338CrossRefGoogle ScholarPubMed
Kayhan, F., Uguz, F., Kayhan, A., & Toktaş, F. I. (2014). Bupropion XL-induced motor and vocal tics. Clinical Neuropharmacology, 37(6), 192193. doi:https://doi.org/10.1097/WNF.0000000000000056CrossRefGoogle ScholarPubMed
Kok, F. M., Groen, Y., Fuermaier, A. B. M., & Tucha, O. (2020). The female side of pharmacotherapy for ADHD-A systematic literature review. PLoS ONE, 15(9), e0239257. https://doi.org/10.1371/journal.pone.0239257CrossRefGoogle ScholarPubMed
Lagerberg, T., Fazel, S., Sjölander, A., Hellner, C., Lichtenstein, P., & Chang, Z. (2022). Selective serotonin reuptake inhibitors and suicidal behaviour: A population-based cohort study. Neuropsychopharmacology, 47(4), 817823. doi:10.1038/s41386-021-01179-zCrossRefGoogle ScholarPubMed
Man, K. K. C., Lau, W. C. Y., Coghill, D., Besag, F. M. C., Cross, J. H., Ip, P., & Wong, I. C. K. (2020). Association between methylphenidate treatment and risk of seizure: A population-based, self-controlled case-series study. The Lancet. Child & Adolescent Health, 4(6), 435443. doi:https://doi.org/10.1016/S2352-4642(20)30100-0CrossRefGoogle ScholarPubMed
Montgomery, S. A. (2005). Antidepressants and seizures: Emphasis on newer agents and clinical implications. International Journal of Clinical Practice, 59(12), 14351440. doi:https://doi.org/10.1111/j.1368-5031.2005.00731.xCrossRefGoogle ScholarPubMed
Murphy, T. K., Segarra, A., Storch, E. A., & Goodman, W. K. (2008). SSRI Adverse events: How to monitor and manage. International Review of Psychiatry (Abingdon, England), 20(2), 203208. https://doi.org/10.1080/09540260801889211CrossRefGoogle ScholarPubMed
Oh, J. E., Zupan, B., Gross, S., & Toth, M. (2009). Paradoxical anxiogenic response of juvenile mice to fluoxetine. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 34(10), 21972207. doi:https://doi.org/10.1038/npp.2009.47CrossRefGoogle ScholarPubMed
Opal, M. D., Klenotich, S. C., Morais, M., Bessa, J., Winkle, J., Doukas, D., … Dulawa, S. M. (2014). Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. Molecular Psychiatry, 19(10), 11061114. doi:https://doi.org/10.1038/mp.2013.144CrossRefGoogle ScholarPubMed
Pan, P. Y., Jonsson, U., Şahpazoğlu Çakmak, S. S., Häge, A., Hohmann, S., Nobel Norrman, H., … Bölte, S. (2022). Headache in ADHD as comorbidity and a side effect of medications: A systematic review and meta-analysis. Psychological Medicine, 52(1), 1425. doi:https://doi.org/10.1017/S0033291721004141CrossRefGoogle Scholar
Patris, M., Bouchard, J. M., Bougerol, T., Charbonnier, J. F., Chevalier, J. F., Clerc, G., … Høpfner Petersen, H. E. (1996). Citalopram versus fluoxetine: A double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice. International Clinical Psychopharmacology, 11(2), 129136.Google ScholarPubMed
Pogorelov, V. M., Rodriguiz, R. M., Cheng, J., Huang, M., Schmerberg, C. M., Meltzer, H. Y., … Wetsel, W. C. (2017). 5-HT2C Agonists modulate schizophrenia-like behaviors in mice. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 42(11), 21632177. doi:https://doi.org/10.1038/npp.2017.52CrossRefGoogle Scholar
Posner, J., Siciliano, F., Wang, Z., Liu, J., Sonuga-Barke, E., & Greenhill, L. (2014). A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression? Psychiatry Research: Neuroimaging, 224(2), 112118. doi:https://doi.org/10.1016/j.pscychresns.2014.08.006CrossRefGoogle ScholarPubMed
Reale, L., Bartoli, B., Cartabia, M., Zanetti, M., Costantino, M. A., & Canevini, M. P.Lombardy ADHD Group (2017). Comorbidity prevalence and treatment outcome in children and adolescents with ADHD. European Child & Adolescent Psychiatry, 26(12), 14431457. doi:https://doi.org/10.1007/s00787-017-1005-zCrossRefGoogle ScholarPubMed
Revet, A., Montastruc, F., Roussin, A., Raynaud, J. P., Lapeyre-Mestre, M., & Nguyen, T. T. H. (2020). Antidepressants and movement disorders: A postmarketing study in the world pharmacovigilance database. BMC Psychiatry, 20(1), 308. doi:https://doi.org/10.1186/s12888-020-02711-zCrossRefGoogle ScholarPubMed
Riglin, L., Leppert, B., Dardani, C., Thapar, A. K., Rice, F., O'Donovan, M. C., … Thapar, A. (2021). ADHD And depression: Investigating a causal explanation. Psychological Medicine, 51(11), 18901897. doi:10.1017/S0033291720000665CrossRefGoogle ScholarPubMed
Romero-Acosta, K., Canals, J., Hernández-Martínez, C., Penelo, E., Zolog, T. C., & Domènech-Llaberia, E. (2013). Age and gender differences of somatic symptoms in children and adolescents*. Journal of Mental Health (Abingdon, England), 22(1), 3341. doi:https://doi.org/10.3109/09638237.2012.734655CrossRefGoogle ScholarPubMed
Smith, V. A., Coffman, C. J., & Hudgens, M. G. (2021). Interpreting the results of intention-to-treat, per-protocol, and as-treated analyses of clinical trials. JAMA, 326(5), 433434. doi:https://doi.org/10.1001/jama.2021.2825CrossRefGoogle ScholarPubMed
Sonnby, K., Åslund, C., Leppert, J., & Nilsson, K. W. (2011). Symptoms of ADHD and depression in a large adolescent population: Co-occurring symptoms and associations to experiences of sexual abuse. Nordic Journal of Psychiatry, 65(5), 315322. doi:10.3109/08039488.2010.545894CrossRefGoogle Scholar
Tost, H., Alam, T., & Meyer-Lindenberg, A. (2010). Dopamine and psychosis: Theory, pathomechanisms and intermediate phenotypes. Neuroscience and Biobehavioral Reviews, 34(5), 689700. doi:https://doi.org/10.1016/j.neubiorev.2009.06.005CrossRefGoogle ScholarPubMed
Van Waes, V., Ehrlich, S., Beverley, J. A., & Steiner, H. (2015). Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: Potential role for 5-HT1B receptor. Neuropharmacology, 89, 7786. doi:https://doi.org/10.1016/j.neuropharm.2014.08.024CrossRefGoogle ScholarPubMed
Walker, Z., Walker, R. W., Robertson, M. M., & Stansfeld, S. (1998). Antidepressant treatment of chronic tension-type headache: A comparison between fluoxetine and desipramine. Headache, 38(7), 523528. doi:https://doi.org/10.1046/j.1526-4610.1998.3807523.xCrossRefGoogle ScholarPubMed
Wang, C., Yuan, Y., Zheng, M., Pan, A., Wang, M., Zhao, M., … Xue, H. (2020). Association of age of onset of hypertension with cardiovascular diseases and mortality. Journal of the American College of Cardiology, 75(23), 29212930. doi:https://doi.org/10.1016/j.jacc.2020.04.038CrossRefGoogle ScholarPubMed
Wichniak, A., Wierzbicka, A., Walęcka, M., & Jernajczyk, W. (2017). Effects of antidepressants on sleep. Current Psychiatry Reports, 19(9), 63. doi:https://doi.org/10.1007/s11920-017-0816-4CrossRefGoogle ScholarPubMed
Wilson, S., & Argyropoulos, S. (2005). Antidepressants and sleep: A qualitative review of the literature. Drugs, 65(7), 927947. doi:https://doi.org/10.2165/00003495-200565070-00003CrossRefGoogle ScholarPubMed
Wolraich, M. L., Hagan, J. F. Jr., Allan, C., Chan, E., Davison, D., Earls, M., … Disorder, A. W. A.-D. H. (2019). Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics, 144(4), e20192528. doi:10.1542/peds.2019-2528CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Kim et al. supplementary material

Kim et al. supplementary material 1

Download Kim et al. supplementary material(PDF)
PDF 399.4 KB
Supplementary material: File

Kim et al. supplementary material

Kim et al. supplementary material 2

Download Kim et al. supplementary material(File)
File 53.1 KB
Supplementary material: File

Kim et al. supplementary material

Kim et al. supplementary material 3

Download Kim et al. supplementary material(File)
File 1.7 MB