+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine

Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine

Cns Drugs 31(3): 199-215

Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death. To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD. We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias. Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p < 0.01; AMP: SMD 0.09, 95% CI 0.03-0.15, p < 0.01; ATX: SMD 0.16, 95% CI 0.04-0.27, p = 0.01). MPH did not have a pre-post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre-post increase of DBP (SMD 0.16, CI 0.03-0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10-0.34, p < 0.01). AMP and ATX were associated with a small to medium statistically significant pre-post increase of HR (AMP: SMD 0.37, CI 0.13-0.60, p < 0.01; ATX: SMD 0.43, CI 0.26-0.60, p < 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects. Statistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.

(PDF emailed within 0-6 h: $19.90)

Accession: 059471789

Download citation: RISBibTeXText

PMID: 28236285

DOI: 10.1007/s40263-017-0410-7

Related references

A pilot study of stimulant medication for adults with attention-deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD: the acute effects of stimulant medication on observed parent-adolescent interactions. Journal of Child and Adolescent Psychopharmacology 24(10): 582-585, 2015

Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review and meta-analysis. Medical Journal of the Islamic Republic of Iran 30: 325, 2016

The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression. International Journal of Environmental Research and Public Health 15(8), 2018

Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. American Journal of Psychiatry 168(11): 1154-1163, 2012

Gray Matter Volume Abnormalities in ADHD: Voxel-Based Meta-Analysis Exploring the Effects of Age and Stimulant Medication. Yearbook of Psychiatry and Applied Mental Health 2013: 38-39, 2013

The Effects of Long-Acting Stimulant and Nonstimulant Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials. Journal of Child and Adolescent Psychopharmacology 28(8): 494-507, 2018

A Signature of Attention-Elicited Electrocortical Activity Distinguishes Response From Non-Response to the Non-Stimulant Atomoxetine in Children and Adolescents With ADHD. Journal of Attention Disorders 23(7): 744-753, 2017

Does stimulant pretreatment modify atomoxetine effects on core symptoms of ADHD in children assessed by quantitative measurement technology?. Journal of Attention Disorders 18(2): 105-116, 2014

Stimulant Use and Cardiovascular Risk Among Children And Adolescents With Adhd: What Product Labeling Does, or Does Not, Tell Us. Value in Health 18(7): A747, 2015

Systematic evidence synthesis of treatments for ADHD in children and adolescents: indirect treatment comparisons of lisdexamfetamine with methylphenidate and atomoxetine. Current Medical Research and Opinion 30(8): 1673-1685, 2015

Effects of stimulant medication on learning in children with ADHD. Journal of Learning Disabilities 24(4): 219-30, 255, 1991

Stimulant and non-stimulant medication in current and future therapy for ADHD. Fortschritte der Neurologie-Psychiatrie 80(3): 130-140, 2012

Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials. Child and Adolescent Psychiatry and Mental Health 7: 19, 2013

Effects of stimulant medication on cognitive performance of children with ADHD. Clinical Pediatrics 44(5): 405-411, 2005

Informed consent and stimulant medication: adolescents' and parents' ability to understand information about benefits and risks of stimulant medication for the treatment of attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology 21(2): 139-148, 2012