How do ADHD drugs compare in children?

In children aged 6-12 years, compared to immediate release (IR) formulations of methylphenidate there is no clear evidence of a difference in efficacy with sustained release (SR) formulations of methylphenidate, mixed amphetamine salts, dextroamphetamine or atomoxetine. A relative, but inconsistent, benefit was found on some outcome measures with the osmotic controlled release formulation of methylphenidate and mixed amphetamine salts compared with methylphenidate IR. [full review]

In younger children (3-5 years), evidence is lacking. [full review] There are mixed results for the use of methylphenidate IR in the short-term, and long-term use might reduce growth rates. [full review]

For more comparisons of ADHD drugs in children and adolescents, please see the Drug Class Review.

How do ADHD drugs compare in safety in children?

• There appears to be no difference in adverse events between IR and SR formulations of methylphenidate in the short term. [full review]
• Dextroamphetamine IR appears to suppress weight gain compared to mephylphenidate IR in the first 1-2 years, with regression to the median percentile for both drugs after 2 years. Changes in weight gain with atomoxetine were similar to methylpehinate IR. [full review]
• Methylphenidate (IR and OROS) and atomoxetine appear to transiently slow height gain (findings are mixed). [full review]
• Atomoxetine is generally linked with higher rates of vomiting, day time sleepiness, nausea, and anorexia, but lower rates of headache compared to stimulants. [full review]
• Rates of insomnia and appetite suppression were not different among the stimulants or atomoxetine, although individual rates varied by drug.
• The rates of adverse events with modafinil are similar compared to methylphenidate IR. [full review]

In teenagers and young adults, the use of stimulant ADHD drugs in childhood is not linked with alcohol abuse, smoking or substance abuse later on in life when comorbid conduct disorder is taken into account. [full review]

Does gender, ethnicity, or the presence of other conditions influence ADHD drugs in children?

Most data are on male, white children. Analysis of the available data suggests that lisdexamfetamine may be less efficacious in girls and in non-white children.

In children who have conditions that commonly occur with ADHD, limited evidence suggests the following drugs are beneficial: atomoxetine in oppositional defiant disorder, methylphenidate IR in a tic disorder, and mixed amphetamine salts IR or methylphenidate IR in bipolar disorder. [full review]

How do ADHD drugs compare in adults?

When directly compared with each other, dextroamphetamine IR and modafinil have similar effects in adults. When compared to placebo, the following drugs are effective in reducing ADHD symptoms in the short-term: atomoxetine, dextroamphetamine (IR, ZR), methylphenidate (IR, SR, ER, XR, OROS), lisdexamfetamine, and mixed amphetamine salts (IR and XR), with limited evidence suggesting that short-acting stimulants have better response than longer-acting stimulants. For improving driving performance outcomes, mephylphenidate IR is consistantly superior to placebo, whereas atomoxetine is not.

For tolerability in adults, common adverse effects include insomnia and loss of appetite. There is no clear evidence that one stimulant is better tolerated than another, or that non-stimulants, such as atomoxetine, are superior to stimulants. [full review]

Drugs included in this review

* Amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, dextroamphetamine sulfate

Further information

This PubMed Clinical Q&A was reviewed by Marian McDonagh, PharmD.

For the full report and evidence tables, please see:
McDonagh MS, Christensen V, Peterson K, et al. Drug Class Review: Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder: Final Report Update 3 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Oct. Available at: http://www.ncbi.nlm.nih.gov/books/NBK47133/.