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Methylphenidate and mortality in children with attention-deficit hyperactivity disorder: population-based cohort study

Published online by Cambridge University Press:  14 July 2020

Vincent Chin-Hung Chen
Affiliation:
Department of Psychiatry, Chiayi Chang Gung Memorial Hospital, Chiayi; and Department of Psychiatry, Chang Gung University, Taoyuan, Taiwan
Hsiang-Lin Chan
Affiliation:
Department of Psychiatry, Chang Gung University, Taoyuan; and Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
Shu-I Wu
Affiliation:
Department of Medicine, Mackay Medical College, Taipei; and Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan
Mong-Liang Lu
Affiliation:
Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taiwan
Michael E. Dewey
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Robert Stewart
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, King's College London; and South London and Maudsley NHS Foundation Trust, London, UK
Charles Tzu-Chi Lee
Affiliation:
Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan
Corresponding
E-mail address:

Abstract

Background

Little is known about methylphenidate (MPH) use and mortality outcomes.

Aims

To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis.

Method

This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4–17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan.

Results

The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67–0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01–1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70–0.98).

Conclusions

MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.

Type
Paper
Copyright
Copyright © The Authors 2020. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

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References

Polanczyk, GV, Salum, GA, Sugaya, LS, Caye, A, Rohde, LA. Annual research review: a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents. J Child Psychol Psychiatry 2015; 56: 345–65.CrossRefGoogle ScholarPubMed
Kessler, RC, Adler, L, Barkley, R, Biederman, J, Conners, CK, Demler, O, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163: 716–23.CrossRefGoogle ScholarPubMed
Huang, CL, Chu, CC, Cheng, TJ, Weng, SF. Epidemiology of treated attention-deficit/hyperactivity disorder (ADHD) across the lifespan in Taiwan: a nationwide population-based longitudinal study. PLoS One 2014; 9(4): e95014.CrossRefGoogle ScholarPubMed
Yoshimasu, K, Barbaresi, WJ, Colligan, RC, Voigt, RG, Killian, JM, Weaver, AL, et al. Childhood ADHD is strongly associated with a broad range of psychiatric disorders during adolescence: a population-based birth cohort study. J Child Psychol Psychiatry 2012; 53: 1036–43.CrossRefGoogle ScholarPubMed
Balazs, J, Kereszteny, A. Attention-deficit/hyperactivity disorder and suicide: a systematic review. World J Psychiatry 2017; 7: 4459.CrossRefGoogle ScholarPubMed
Altun, C, Guven, G, Akgun, OM, Acikel, C. Dental injuries and attention-deficit/hyperactivity disorder in children. Spec Care Dentist 2012; 32: 184–9.CrossRefGoogle ScholarPubMed
Ertan, C, Ozcan, OO, Pepele, MS. Paediatric trauma patients and attention deficit hyperactivity disorder: correlation and significance. Emerg Med J 2012; 29: 911–4.CrossRefGoogle ScholarPubMed
Tai, YM, Gau, SS, Gau, CS. Injury-proneness of youth with attention-deficit hyperactivity disorder: a national clinical data analysis in Taiwan. Res Dev Disabil 2013; 34: 1100–8.CrossRefGoogle ScholarPubMed
Vaa, T. ADHD and relative risk of accidents in road traffic: a meta-analysis. Accid Anal Prev 2014; 62: 415–25.CrossRefGoogle ScholarPubMed
Curry, AE, Metzger, KB, Pfeiffer, MR, Elliott, MR, Winston, FK, Power, TJ. Motor vehicle crash risk among adolescents and young adults with attention-deficit/hyperactivity disorder. JAMA Pediatrics 2017; 171: 756–63.CrossRefGoogle Scholar
Barbaresi, WJ, Colligan, RC, Weaver, AL, Voigt, RG, Killian, JM, Mortality, KS. ADHD, and psychosocial adversity in adults with childhood ADHD: a prospective study. Pediatrics 2013; 131: 637–44.CrossRefGoogle ScholarPubMed
Dalsgaard, S, Ostergaard, SD, Leckman, JF, Mortensen, PB, Pedersen, MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. Lancet 2015; 385: 2190–6.CrossRefGoogle ScholarPubMed
London, AS, Landes, SD. Attention deficit hyperactivity disorder and adult mortality. Prev Med 2016; 90: 810.CrossRefGoogle ScholarPubMed
Chen, VC, Chan, HL, Wu, SI, Lee, M, Lu, ML, Liang, HY, et al. Attention-deficit/hyperactivity disorder and mortality risk in Taiwan. JAMA Network Open 2019; 2(8): e198714.CrossRefGoogle ScholarPubMed
Cairney, J. Deficits in attention, motor control, and perception and increased risk of injury in children. Dev Med Child Neurol 2014; 56: 1040–1.CrossRefGoogle ScholarPubMed
Jerome, L, Habinski, L, Segal, A. Attention-deficit/hyperactivity disorder (ADHD) and driving risk: a review of the literature and a methodological critique. Curr Psychiatry Rep 2006; 8: 416–26.CrossRefGoogle Scholar
Vaughan, B, Kratochvil, CJ. Pharmacotherapy of pediatric attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 2012; 21: 941–55.CrossRefGoogle ScholarPubMed
MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 1999; 56: 1073–86.CrossRefGoogle Scholar
Man, KK, Chan, EW, Coghill, D, Douglas, I, Ip, P, Leung, LP, et al. Methylphenidate and the risk of trauma. Pediatrics 2015; 135: 40–8.CrossRefGoogle ScholarPubMed
Mikolajczyk, R, Horn, J, Schmedt, N, Langner, I, Lindemann, C, Garbe, E. Injury prevention by medication among children with attention-deficit/hyperactivity disorder: a case-only study. JAMA Pediatrics 2015; 169: 391–5.CrossRefGoogle ScholarPubMed
Chang, Z, Quinn, PD, Hur, K, Gibbons, RD, Sjolander, A, Larsson, H, et al. Association between medication use for attention-deficit/hyperactivity disorder and risk of motor vehicle crashes. JAMA Psychiatry 2017; 74: 597603.CrossRefGoogle ScholarPubMed
Ruiz-Goikoetxea, M, Cortese, S, Aznarez-Sanado, M, Magallon, S, Alvarez Zallo, N, Luis, EO, et al. Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: a systematic review and meta-analysis. Neurosci Biobehav Rev 2018; 84: 6371.CrossRefGoogle ScholarPubMed
Ljung, T, Chen, Q, Lichtenstein, P, Larsson, H. Common etiological factors of attention-deficit/hyperactivity disorder and suicidal behavior: a population-based study in Sweden. JAMA Psychiatry 2014; 71: 958–64.CrossRefGoogle ScholarPubMed
Liang, SH, Yang, YH, Kuo, TY, Liao, YT, Lin, TC, Lee, Y, et al. Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: a Taiwan nationwide population-based cohort study. Res Dev Disabil 2018; 72: 96105.CrossRefGoogle ScholarPubMed
Cortese, S, Adamo, N, Del Giovane, C, Mohr-Jensen, C, Hayes, AJ, Carucci, S, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry 2018; 5: 727–38.CrossRefGoogle ScholarPubMed
Storebo, OJ, Pedersen, N, Ramstad, E, Kielsholm, ML, Nielsen, SS, Krogh, HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev 2018; 5: CD012069.Google ScholarPubMed
Dalsgaard, S, Kvist, AP, Leckman, JF, Nielsen, HS, Simonsen, M. Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study. J Child Adolesc Psychopharmacol 2014; 24: 302–10.CrossRefGoogle ScholarPubMed
Mazza, M, D'Ascenzo, F, Davico, C, Biondi-Zoccai, G, Frati, G, Romagnoli, E, et al. Drugs for attention deficit-hyperactivity disorder do not increase the mid-term risk of sudden death in children: a meta-analysis of observational studies. Int J Cardiol 2013; 168: 4320–1.CrossRefGoogle Scholar
Chang, Z, Ghirardi, L, Quinn, PD, Asherson, P, D'Onofrio, BM, Larsson, H. Risks and benefits of attention-deficit/hyperactivity disorder medication on behavioral and neuropsychiatric outcomes: a qualitative review of pharmacoepidemiology studies using linked prescription databases. Biol Psychiatry 2019; 86: 335–43.CrossRefGoogle ScholarPubMed
Olfson, M, Druss, BG, Marcus, SC. Trends in mental health care among children and adolescents. N Engl J Med 2015; 373: 1079.Google ScholarPubMed
Hechtman, L. Long-term treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Curr Psychiatry Rep 2006; 8: 398408.CrossRefGoogle Scholar
McCarthy, S, Cranswick, N, Potts, L, Taylor, E, Wong, IC. Mortality associated with attention-deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children, adolescents and young adults using the general practice research database. Drug Saf 2009; 32: 1089–96.CrossRefGoogle Scholar
Chen, Q, Sjolander, A, Runeson, B, D'Onofrio, BM, Lichtenstein, P, Larsson, H. Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study. BMJ 2014; 348: g3769.CrossRefGoogle ScholarPubMed
Kaur, P, Muthuraman, A, Kaur, M. The implications of angiotensin-converting enzymes and their modulators in neurodegenerative disorders: current and future perspectives. ACS Chem Neurosci 2015; 6: 508–21.CrossRefGoogle ScholarPubMed
Lee, MJ, Yang, KC, Shyu, YC, Yuan, SS, Yang, CJ, Lee, SY, et al. 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 2016; 189: 110–7.CrossRefGoogle ScholarPubMed
Ngwa, JS, Cabral, HJ, Cheng, DM, Pencina, MJ, Gagnon, DR, LaValley, MP, et al. A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study. BMC Med Res Methodol 2016; 16: 148.CrossRefGoogle Scholar
Gray, B. cmprsk: Subdistribution Analysis of Competing Risks. CRAN, 2014 (https://cran.r-project.org/web/packages/cmprsk/index.html).Google Scholar
Fine, JP, Gray, RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496509.CrossRefGoogle Scholar
R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, 2019 (https://www.R-project.org/).Google Scholar
Berger, S. Attention deficit hyperactivity disorder medications in children with heart disease. Curr Opin Pediatr 2016; 28: 607–12.CrossRefGoogle ScholarPubMed
Shin, JY, Roughead, EE, Park, BJ, Pratt, NL. Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. BMJ 2016; 353: i2550.CrossRefGoogle Scholar
Winterstein, AG, Gerhard, T, Kubilis, P, Saidi, A, Linden, S, Crystal, S, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ 2012; 345: e4627.CrossRefGoogle ScholarPubMed
Man, KKC, Ip, P, Chan, EW, Law, SL, Leung, MTY, Ma, EXY, et al. Effectiveness of pharmacological treatment for attention-deficit/hyperactivity disorder on physical injuries: a systematic review and meta-analysis of observational studies. CNS Drugs 2017; 31: 1043–55.CrossRefGoogle ScholarPubMed
Chen, VC, Yang, YH, Liao, YT, Kuo, TY, Liang, HY, Huang, KY, et al. The association between methylphenidate treatment and the risk for fracture among young ADHD patients: a nationwide population-based study in Taiwan. PLoS One 2017; 12(3): e0173762.CrossRefGoogle ScholarPubMed
Mannuzza, S, Klein, RG, Truong, NL, Moulton, JL 3rd, Roizen, ER, Howell, KH, et al. Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry 2008; 165: 604–9.CrossRefGoogle ScholarPubMed
Lee, CT, Chen, VC, Tan, HK, Chou, SY, Wu, KH, Chan, CH, et al. Suicide and other-cause mortality among heroin users in Taiwan: a prospective study. Addict Behav 2013; 38: 2619–23.CrossRefGoogle ScholarPubMed
Russell, AE, Ford, T, Russell, G. Barriers and predictors of medication use for childhood ADHD: findings from a UK population-representative cohort. Soc Psychiatry Psychiatr Epidemiol 2019; 54: 1555–64.CrossRefGoogle ScholarPubMed
Rucklidge, JJ. Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 2010; 33: 357–73.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Larsson, H. Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med 2013; 368: 776.Google ScholarPubMed
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