ADHD meds not necessarily more effective in higher doses

When children with ADHD don’t respond well to methylphenidate, doctors often increase the dose. Now a new review shows that increasing the dose may not always be the best option, as it may have no effect on some of the functional impairments associated with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder, characterised by symptoms such as inattention, hyperactivity and impulsivity. Worldwide, around 5% of children and adolescents suffer from ADHD.

Diagnosis of ADHD requires that a patient exhibit at least six behavioural symptoms; treatment is normally judged on how well these behavioural symptoms are improved. However, children with ADHD can also be characterised by looking at functional impairments such as neurocognitive functioning, including inhibitory control — a measure of how they keep their impulsiveness under control.

Methylphenidate (MPH, sold under the trade name of Ritalin) has been commonly used as a first line medication to treat children with ADHD since the 1990s — but while it is generally effective and well tolerated, around 30% of children taking MPH don’t respond to standard doses, often leading doctors to consider increasing the dose. Furthermore, MPH carries the risk of side effects, including growth retardation and difficulty in gaining weight, which may become more significant at increased dose and with long-term use.

To understand and distil the effects of the drug on children with ADHD, Karen Vertessen and colleagues at the Vrije Universiteit Amsterdam undertook a review of all the scientific literature to dose effects of MPH on inhibitory control in children and adolescents. They identified 18 studies, comprising in total 606 subjects with ADHD, and classified the MPH doses reported as low, medium or high.

The researchers found that a medium dose of MPH had the strongest beneficial effects on inhibitory control. Increasing the dose past medium had some effect on behavioural factors, but not on inhibitory control. The outcome was presented at the 32nd ECNP (European College of Neuropsychopharmacology) Congress, held in Copenhagen in early September.

“Scientifically, this is an interesting result,” Vertessen said. “Generally, high doses of MPH does not help the child or adolescent keep their inhibitions under better control, although an increased dose, in general, does have a greater effect on the core behavioural symptoms of ADHD.

“Even though inhibitory control is just one aspect of impulsivity, we suggest that medically we need to be cautious about just increasing the dose when a child does not instantly respond to the drugs. Children are more vulnerable than adults in these cases, especially since they will be just beginning to receive treatment, and so many treatment variables will still need to be established. If clinicians decide to start therapy with MPH, they need to keep a close eye on the patient and objectively evaluate every dose, to make sure that the higher dose is actually having an effect.

“Current ADHD evaluation only uses behavioural outcomes, whereas we suggest adding neurocognitive outcomes to this evaluation, given that these outcomes are important for, among others, academic functioning. In other words, checking for whether or not MPH is dealing with inhibitory control might allow us to see if increasing the dose makes sense. To see to what extent these findings might have a clinical impact, we are currently investigating the other most relevant neurocognitive factors related to ADHD.

Image credit: ©stock.adobe.com/au/Photographee.eu