Skip to main content

Advertisement

SpringerLink
Log in

Childhood methylphenidate adherence as a predictor of antidepressants use during adolescence

  • Original Contribution
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

Methylphenidate (MPH) is a common and effective treatment for attention deficit hyperactivity disorder (ADHD), but little is known about the relationship between early childhood intake of MPH and onset of antidepressant treatment during adolescence. The study aimed to examine whether adherence to MPH during early childhood predicts the initiation of antidepressants during adolescence. This is a 12-year historical prospective nationwide cohort study of children enrolled in an integrated care system who were first prescribed MPH between the ages of 6 and 8 years (N = 6830). We tested for an association between their adherence to MPH during early childhood (as indicated by medication possession ratio from MPH onset through the age of twelve) and the likelihood of being prescribed any antidepressant during adolescence (age 13–18). As all country citizens are covered by mandatory health insurance, and full services are provided by one of the four integrated care systems, data regarding patients’ diagnoses, prescriptions, and medical purchases are well documented. Logistic regression analysis indicated that those with higher adherence to MPH had a 50% higher risk (95% CI 1.16–1.93) of receiving antidepressants during adolescence when controlling for other comorbid psychiatric conditions and parental use of antidepressants. In this large-scale longitudinal study, MPH adherence during early childhood emerged as a predictor for antidepressant treatment during adolescence, which may reflect increased emotional and behavioral dysregulation in this group. The highly adherent patients are at higher risk and should be clinically monitored more closely, particularly into adolescence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. APA (2013) The diagnostic and statistical manual of mental disorders. American Psychiatric Association, Arlington, VA

    Google Scholar 

  2. Barnard-Brak L, Roberts B, Valenzuela E (2018) Examining breaks and resistance in medication adherence among adolescents with ADHD as associated with school outcomes. J Attent Disord

  3. Barner JC, Khoza S, Oladapo A (2011) ADHD medication use, adherence, persistence and cost among Texas Medicaid children. Curr Med Res Opin 27:13–22

    Article  Google Scholar 

  4. Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV (2009) Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics 124:71–78

    Article  Google Scholar 

  5. Biederman J, Newcorn J, Sprich S (1991) Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 5:564–577

    Google Scholar 

  6. Bloch Y, Aviram S, Segev A, Nitzan U, Levkovitz Y, Braw Y, Mimouni Bloch A (2017) Methylphenidate reduces state anxiety during a continuous performance test that distinguishes adult ADHD patients from controls. J Atten Disord 21:46–51

    Article  Google Scholar 

  7. Brinkman WB, Sherman SN, Zmitrovich AR, Visscher MO, Crosby LE, Phelan KJ, Donovan EF (2012) In their own words: adolescent views on ADHD and their evolving role managing medication. Acad Pediatr 12:53–61

    Article  Google Scholar 

  8. Brinkman WB, Sucharew H, Majcher JH, Epstein JN (2018) Predictors of medication continuity in children with ADHD. Pediatrics 141:e20172580

    Article  Google Scholar 

  9. Chilakamarri JK, Filkowski MM, Nassir Ghaemi S (2011) Misdiagnosis of bipolar disorder in children and adolescents: a comparison with ADHD and major depressive disorder. Ann Clin Psychiatry 23:25–29

    PubMed  Google Scholar 

  10. Childress AC, Wigal SB, Brams MN, Turnbow JM, Pincus Y, Belden HW, Berry SA (2018) Efficacy and safety of amphetamine extended-release oral suspension in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 28:306–313

    Article  CAS  Google Scholar 

  11. Chinitz D, Shalev C, Galai N, Israeli A (1998) Israel's basket of health services: the importance of being explicitly implicit. BMJ 317:1005–1008

    CAS  PubMed  Google Scholar 

  12. Clarfield AM, Manor O, Nun GB, Shvarts S, Azzam ZS, Afek A, Basis F, Israeli A (2017) Health and health care in Israel: an introduction. The Lancet 389: 2503-2513

    Article  Google Scholar 

  13. Copeland W, Shanahan L, Erkanli A, Costello EJ, Angold A (2013) Indirect comorbidity in childhood and adolescence. Front Psychiatry 4:144

    Article  Google Scholar 

  14. Coughlin CG, Cohen SC, Mulqueen JM, Ferracioli-Oda E, Stuckelman ZD, Bloch MH (2015) Meta-analysis: reduced risk of anxiety with psychostimulant treatment in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 25:611–617

    Article  CAS  Google Scholar 

  15. Daviss WB, Birmaher B, Diler RS, Mintz J (2008) Does pharmacotherapy for attention-deficit/hyperactivity disorder predict risk of later major depression? J Child Adolesc Psychopharmacol 18:257–264

    Article  Google Scholar 

  16. Deshpande S, Quek RG, Forbes CA, de Kock S, Kleijnen J, Gandra SR, Simpson RJ Jr (2017) A systematic review to assess adherence and persistence with statins. Curr Med Res Opin 33:769–778

    Article  Google Scholar 

  17. Gajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, Xie J (2014) Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder—a systematic literature review. Neuropsychiatr Dis Treat 10:1543

    PubMed  PubMed Central  Google Scholar 

  18. Gau S, Chen S-J, Chou W-J, Cheng H, Tang C-S, Chang H-L, Tzang R-F, Wu Y-Y, Huang Y-F, Chou M-C (2008) National survey of adherence, efficacy, and side effects of methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Clin Psychiatry 69:131–140

    Article  CAS  Google Scholar 

  19. Golubchik P, Kodesh A, Weizman A (2013) Attention-deficit/hyperactivity disorder and comorbid subsyndromal depression: what is the impact of methylphenidate on mood? Clin Neuropharmacol 36:141–145

    Article  CAS  Google Scholar 

  20. Groenman AP, Schweren LJ, Dietrich A, Hoekstra PJ (2017) An update on the safety of psychostimulants for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Drug Saf 16:455–464

    Article  CAS  Google Scholar 

  21. Inglis SK, Carucci S, Garas P, Häge A, Banaschewski T, Buitelaar J, Dittmann R, Falissard B, Hollis C, Kovshoff H, ADDUCE Consortium (2016) Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. BMJ open 6:e010433. https://doi.org/10.1136/bmjopen-2015-010433

    Article  CAS  Google Scholar 

  22. Kortekaas-Rijlaarsdam AF, Luman M, Sonuga-Barke E, Oosterlaan J (2018) Does methylphenidate improve academic performance? A systematic review and meta-analysis. Eur Child Adolesc Psychiatry

  23. Larson K, Russ SA, Kahn RS, Halfon N (2011) Patterns of comorbidity, functioning, and service use for US children with ADHD, 2007. Pediatrics 127:462–470

    Article  Google Scholar 

  24. Lee H, Kim SW, Kim JM, Shin IS, Yang SJ, Yoon JS (2005) Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury. Hum Psychopharmacol Clin Exp 20:97–104

    Article  CAS  Google Scholar 

  25. Lee MJ, Yang KC, Shyu YC, Yuan SS, Yang CJ, Lee SY, Lee TL, Wang L- (2016) Attention-deficit hyperactivity disorder, its treatment with medication and the probability of developing a depressive disorder: a nationwide population-based study in Taiwan. J Affect Disord 189:110–117

    Article  Google Scholar 

  26. Lundervold AJ, Hinshaw SP, Sørensen L, Posserud M-B (2016) Co-occurring symptoms of attention deficit hyperactivity disorder (ADHD) in a population-based sample of adolescents screened for depression. Bmc Psychiatry 16(46):1–10

    Google Scholar 

  27. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67:220–229

    Article  Google Scholar 

  28. Man KK, Coghill D, Chan EW, Lau WC, Hollis C, Liddle E, Banaschewski T, McCarthy S, Neubert A, Sayal K (2017) Association of risk of suicide attempts with methylphenidate treatment. Jama Psychiatry 74:1048–1055

    Article  Google Scholar 

  29. Mannuzza S, Klein RG, Truong NL, Moulton PD III, John L, Roizen ER, Howell KH, Castellanos FX (2008) Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry 165:604–609

    Article  Google Scholar 

  30. Manor I, Gutnik I, Ben-Dor DH, Apter A, Sever J, Tyano S, Weizman A, Zalsman G (2010) Possible association between attention deficit hyperactivity disorder and attempted suicide in adolescents—a pilot study. Eur Psychiatry 25:146–150

    Article  CAS  Google Scholar 

  31. McCabe SE, Dickinson K, West BT, Wilens TE (2016) Age of onset, duration, and type of medication therapy for attention-deficit/hyperactivity disorder and substance use during adolescence: a multi-cohort national study. J Am Acad Child Adolesc Psychiatry 55:479–486

    Article  Google Scholar 

  32. Murray ML, Insuk S, Banaschewski T, Neubert AC, McCarthy S, Buitelaar JK, Coghill D, Dittmann RW, Konrad K, Panei P (2013) An inventory of European data sources for the long-term safety evaluation of methylphenidate. Eur Child Adolesc Psychiatry 22:605–618

    Article  Google Scholar 

  33. Pappadopulos E, Jensen PS, Chait AR, Arnold LE, Swanson JM, Greenhill LL, Hechtman L, Chuang S, Wells KC, Pelham W (2009) Medication adherence in the MTA: saliva methylphenidate samples versus parent report and mediating effect of concomitant behavioral treatment. J Am Acad Child Adolesc Psychiatry 48:501–510

    Article  Google Scholar 

  34. Patel NC, Crismon ML, Hoagwood K, Johnsrud MT, Rascati KL, Wilson JP, Jensen PS (2005) Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 44:548–556

    Article  Google Scholar 

  35. Rasmussen K, Palmstierna T, Levander S (2015) Differences in psychiatric problems and criminality between individuals treated with central stimulants before and after adulthood. J Atten Disord :1–8

  36. Reale L, Bartoli B, Cartabia M, Zanetti M, Costantino MA, Canevini MP, Termine C, Bonati M, Group LA (2017) Comorbidity prevalence and treatment outcome in children and adolescents with ADHD. Eur Child Adolesc Psychiatry 26:1443–1457

    Article  Google Scholar 

  37. Scholle O, Banaschewski T, Enders D, Garbe E, Riedel O (2018) Use and characteristics of antipsychotic/methylphenidate combination therapy in children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 28:306–313

    Article  Google Scholar 

  38. Schrantee A, Bouziane C, Bron E, Klein S, Bottelier M, Kooij J, Rombouts S, Reneman L (2017) Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder. Brain Imaging and Behavior:1–9

  39. Schrantee A, Tamminga HG, Bouziane C, Bottelier MA, Bron EE, Mutsaerts H-JM, Zwinderman AH, Groote IR, Rombouts SA, Lindauer RJ (2016) Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder: a randomized clinical trial. JAMA Psychiatry 73:955–962

    Article  Google Scholar 

  40. Shaw P, Stringaris A, Nigg J, Leibenluft E (2014) Emotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry 171:276–293

    Article  Google Scholar 

  41. Song Q-Y, Guo L-T (2013) Trends in the prescribing of psychotropic medications for inpatient children and adolescents, 2000–2010: a study from China. Int Clin Psychopharmacol 28:193–199

    Article  Google Scholar 

  42. Spencer TJ, Biederman J, Mick E (2007) Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. Ambul Pediatr 7:73–81

    Article  Google Scholar 

  43. Subcommittee on Attention-Deficit, Hyperactivity Disorder; Steering Committee on Quality Improvement and Management WM, Brown L, Brown RT, DuPaul G, Earls M, Feldman HM, Ganiats TG, Kaplanek B, Meyer B, Perrin J, Pierce K, Reiff M, Stein MT, Visser S. (2011) ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 128:2011–2654

    Google Scholar 

  44. Tamblyn R, Lavoie G, Petrella L, Monette J (1995) The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec. J Clin Epidemiol 48:999–1009

    Article  CAS  Google Scholar 

  45. Thomas R, Sanders S, Doust J, Beller E, Glasziou P (2015) Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics 135:e994–e1001

    Article  Google Scholar 

  46. Toomey SL, Sox CM, Rusinak D, Finkelstein JA (2012) Why do children with ADHD discontinue their medication? Clin Pediatr 51:763–769

    Article  Google Scholar 

  47. Urban KR, Gao WJ (2014) Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain. Front Syst Neurosci 8:38

    Article  Google Scholar 

  48. Visser SN, Danielson ML, Bitsko RH, Holbrook JR, Kogan MD, Ghandour RM, Perou R, Blumberg SJ (2014) Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003–2011. J Am Acad Child Adolesc Psychiatry 53(34–46):e32

    Google Scholar 

  49. Wang LJ, Shyu YC, Yuan SS, Yang CJ, Yang KC, Lee T-, Lee SY (2016) Attention-deficit hyperactivity disorder, its pharmacotherapy, and the risk of developing bipolar disorder: A nationwide population-based study in Taiwan. J Psychiatr Res 72:6–14

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Nir Madjar and Dan Shlosberg contributed equally.

Authors and Affiliations

  1. Faculty of Social Sciences, School of Education, Bar-Ilan University, 5290002, Ramat Gan, Israel

    Nir Madjar

  2. Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel

    Dan Shlosberg, Maya Leventer-Roberts, Amichay Akriv, Adi Ghilai & Moshe Hoshen

  3. Department of Pediatrics and Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Maya Leventer-Roberts

  4. Geha Mental Health Center, Petah Tikva, Israel

    Dan Shlosberg, Amir Krivoy, Gil Zalsman & Gal Shoval

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Amir Krivoy, Gil Zalsman & Gal Shoval

  6. Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York, NY, USA

    Gil Zalsman

Authors
  1. Nir Madjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Shlosberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maya Leventer-Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amichay Akriv
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adi Ghilai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Moshe Hoshen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amir Krivoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gil Zalsman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gal Shoval
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nir Madjar.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Appendix A

Appendix A

Variables included in the final model predicting dispensed prescription of ADM (unadjusted).

Variable

Coefficient

95% CI

MPH adherence

1.26

1.04–1.52

Antipsychotics

1.98

1.65–2.39

Parental ADM use

3.51

2.81–4.36

  1. MPH methylphenidate, ADM antidepressant medications.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Madjar, N., Shlosberg, D., Leventer-Roberts, M. et al. Childhood methylphenidate adherence as a predictor of antidepressants use during adolescence. Eur Child Adolesc Psychiatry 28, 1365–1373 (2019). https://doi.org/10.1007/s00787-019-01301-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-019-01301-z

Keywords

Search

Navigation