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Best First-Line ADHD Medications for Children, Adults: Study Results

The most effective first-line, short-term ADHD medication is methylphenidate for children and adolescents, and amphetamines for adults, according to a new study.



August 14, 2018

A new network meta-analyses of seven ADHD medications suggests that methylphenidate in children and adolescents and amphetamines in adults are the most effective, first-line, short-term treatment for ADHD. Results were recently published in The Lancet Psychiatry.1

In the past few decades, prescriptions for ADHD medications have increased significantly in the United States2 and abroad.3 Americans alone spend $143-$266 billion4 annually on ADHD treatment and management. Yet, the safety and efficacy of ADHD medications remain controversial, and no clear guidelines exist for first-line treatment across age groups. For these reasons, researchers from the UK undertook a systemic review and network meta-analysis of 133 double-blind, randomized, controlled trials designed to compare the effectiveness and tolerability of oral monotherapy for ADHD in children, adolescents, and adults.

The study compared amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo over 12 weeks of treatment. Primary outcomes were drug effectiveness (change in severity of ADHD core symptoms based on teachers’ and clinicians’ ratings) and tolerability (proportion of participants who left the study due to side effects).

Drug effectiveness was reviewed in 10,068 children and adolescents, and in 8,131 adults; side effects were evaluated in 11,018 children and adolescents, and 5,362 adults.

For children and adolescents, all drugs were superior to placebo with respect to ADHD core symptoms rated by clinicians. However, according to teachers’ ratings, only methylphenidate and modafinil were superior to placebo.

For adults, with the exception of modafinil, clinicians rated amphetamines, methylphenidate, bupropion, and atomoxetine as superior to placebo in controlling ADHD symptoms. Data were not available for guanfacine and clonidine.

Overall, ADHD drugs were more effective and better tolerated in children and adolescents than they were in adults; the cause of this discrepancy is unknown.

Amphetamines, methylphenidate, atomoxetine, and modafinil caused weight loss in children, adolescents, and adults. Amphetamines and atomoxetine increased blood pressure in children and adolescents, and methylphenidate increased blood pressure in adults.

In the end, methylphenidate produced the best symptom control with the fewest side effects for children and adolescents, and amphetamines produced the best results for adults. However, the study duration was limited to 12 weeks, and researchers stressed that more studies are needed to evaluate the long-term effects of ADHD medications. Additionally, this study compared monotherapy to placebo, and the authors stressed the need for additional well designed head-to-head drug comparison studies.

“Medication can be an important tool for people with ADHD, and our study illustrates that, in the short term, these can be effective and safe treatment options for children, adolescents and adults,” said Dr. Andrea Cipriani, from the department of psychiatry at the University of Oxford in United Kingdom, in a journal news release.5 “Environmental modifications — such as changes made to minimize the impact of ADHD in day-to-day living — and non-pharmacological therapies should be considered first in ADHD treatment, but for people who require drug treatments, our study finds that methylphenidate should be the first drug offered for children and adolescents, and amphetamines should be the first drug offered for adults.”

This study was unable to differentiate the effects of ADHD medications between children (aged 5-12 years) and adolescents (aged 13-18 years), noted Anne Arnett, Ph.D., and Mark Stein, Ph.D., from the psychiatry and behavioral sciences center on human development and disability at the University of Washington in Seattle, in an accompanying editorial.6 “The network meta-analysis was unable to address a major challenge in ADHD treatment, which is the high rate of discontinuation that occurs around puberty despite continuation and even increased severity of impairments at that age,” they stated.

The top three common questions asked by people with ADHD are whether to start a medication, and if so which one, and for how long. While the present study provides little to no data for how long to use an ADHD medication, if does include “general support for short-term medication use, [and provides] basic guidelines about first-line medications based on age,” noted Drs. Arnett and Stein.


1Cortese S, Adamo N, Del Giovane C, 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 Aug 7. doi: 10.1016/S2215-0366(18)30269-4

2Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D. Trends of outpatient prescription drug utilization in US children, 2002-2010. Pediatrics. 2012 Jul;130(1):23-31. doi: 10.1542/peds.2011-2879

3Renoux C, Shin JY, Dell’Aniello S, Fergusson E, Suissa S. Prescribing trends of attention-deficit hyperactivity disorder (ADHD) medications in UK primary care, 1995-2015. Br J Clin Pharmacol. 2016 Sep;82(3):858-868. https://doi.org/10.1111/bcp.13000

4Doshi JA, Hodgkins P, Kahle J et al. Economic impact of childhood and adult attention-deficit/hyperactivity disorder in the United States. J Am Acad Child Adolesc Psychiatry. 2012 Oct;51(10):990-1002.e2. doi: 10.1016/j.jaac.2012.07.008

5The Lancet. ADHD medications: Of all available drugs, methylphenidate should be first option for short-term treatment in children. ScienceDaily. Published August 7, 2018. Accessed August 9, 2018.

6Arnett A, Stein M. Refining treatment choices for ADHD. Lancet Psychiatry. 2018 Aug 7. doi: 10.1016/S2215-0366(18)30295-5

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