Efficacy and Safety of Methylphenidate and Atomoxetine in Medication-Naive Children with Attention-Deficit Hyperactivity Disorder in a Real-World Setting

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background and Objective

Methylphenidate (MPH) and atomoxetine (ATX) are the most common medications used to treat attention-deficit hyperactivity disorder (ADHD) in China; however, despite this, there is still a paucity of studies comparing their efficacy and safety, particularly for different characteristics. To address the lack of research, a real-world prospective cohort study was conducted to examine these properties of MPH and ATX, and to analyze correlations associated with age, sex, and different ADHD presentation.

Methods

Children with ADHD meeting the eligibility criteria were recruited from January 2016 to July 2021. Study participants were treated with either MPH or ATX prescribed in the real-world setting, and were followed up for 26 weeks. Clinical efficacy response and adverse events (AEs) were recorded and measured. Subgroup analysis was performed to examine the efficacy response and AEs associated with age, sex, and different ADHD presentation.

Results

A total of 1050 children were recruited and 29 children were lost to follow-up. Of the 1021 children remaining, 533 were treated with MPH and 488 were treated with ATX. No significant differences were found in intelligence quotient, age, sex, or ADHD presentation between the MPH- and ATX-treated groups ( p > 0.05). The response rates were 84.6% in the MPH-treated group and 63.3% in the ATX-treated group. Subgroup analysis of response rate demonstrated that the treatment effect of MPH over ATX was consistent across subgroups except in the girls (odds ratio [OR] 2.09, 95% confidence interval [CI] 0.97–4.7) and the hyperactive/impulsive presentation group (OR 2.88, 95% CI 0.77–12.76). A total of 47.8% of children experienced AEs during MPH treatment, significantly lower than the rate of 56.8% during ATX treatment ( p < 0.05). The incidence of AEs in the MPH-treated group was higher in young children (<8 years: 56.8%; 8–10 years: 47.2%) and lower in children over 10 years of age (29.0%).

Conclusions

Overall, MPH was more effective and better tolerated than ATX. The incidence of AEs in children treated with MPH varied with age, and was higher in young children and lower in children over 10 years of age.

Related collections

Most cited references 46

Record: found
Abstract: found
Article: not found

Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.

Rae Thomas, Sharon Sanders, Jenny Doust … (2015)

Overdiagnosis and underdiagnosis of attention-deficit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence.

0 comments Cited 482 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis

Samuele Cortese, Nicoletta Adamo, Cinzia Del Giovane … (2018)

Summary Background The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults. Methods We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976. Findings 133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD −1·02, 95% CI −1·19 to −0·85 for amphetamines, −0·78, −0·93 to −0·62 for methylphenidate, −0·56, −0·66 to −0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD −0·82, 95% CI −1·16 to −0·48) and modafinil (−0·76, −1·15 to −0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD −0·79, 95% CI −0·99 to −0·58), methylphenidate (−0·49, −0·64 to −0·35), bupropion (−0·46, −0·85 to −0·07), and atomoxetine (−0·45, −0·58 to −0·32), but not modafinil (0·16, −0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4·25), methylphenidate (2·39, 1·40–4·08), and modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs −0·46 to −0·24) and adults (−0·94 to −0·29). We did not find sufficient data for the 26-week and 52-week timepoints. Interpretation Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. Funding Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.

0 comments Cited 427 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Is Open Access

The World Federation of ADHD International Consensus Statement: 208 Evidence-based Conclusions about the Disorder

Stephen V. Faraone, Tobias Banaschewski, David Coghill … (2021)

Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.

0 comments Cited 376 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Xiu Xu: xuxiu@fudan.edu.cn

Kaifeng Zhang: zhkf2021@126.com

Journal

Journal ID (nlm-ta): Drugs R D

Journal ID (iso-abbrev): Drugs R D

Title: Drugs in R&D

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1174-5886

ISSN (Electronic): 1179-6901

Publication date (Electronic): 20 November 2023

Publication date PMC-release: 20 November 2023

Publication date (Print): March 2024

Volume: 24

Issue: 1

Pages: 29-39

Affiliations

[1 ]Department of Child Healthcare, Children’s Hospital of Fudan University, National Children’s Medical Center, ( https://ror.org/05n13be63) Shanghai, China

[2 ]Department of Pediatrics, Taixing People’s Hospital, ( https://ror.org/02ez0zm48) Taizhou, China

[3 ]Department of Pediatrics, Fudan University Minhang Hospital, ( https://ror.org/013q1eq08) Shanghai, China

Article

Publisher ID: 445

DOI: 10.1007/s40268-023-00445-3

PMC ID: 11035522

PubMed ID: 37982991

SO-VID: 58d21672-0b75-4f86-9724-a45e50946c2a

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date accepted : 2 October 2023

Funding

Funded by: Key Subject Construction Project of Shanghai Municipal Health Commission

Award ID: No. shslczdzk02903

Award Recipient : Xiu Xu

Custom metadata

Data availability:

Comments

Comment on this article

Cited by 3

See all cited by

Most referenced authors 679

See all reference authors