More evidence needed to inform ADHD medication guidelines

The authors of a new study led by the University of Sydney suggest a lack of clarity on appropriate maximum dose limits for stimulant medication for Attention Deficit Hyperactivity Disorder (ADHD) could be confusing for doctors, with some patients potentially not receiving sufficient dosages.

ADHD affects up to 10 percent of children and is charactered by inattention, impulsive behaviour and hyperactivity. Left untreated it can lead to severe educational, social and emotional problems in adulthood.

The study’s senior author and paediatrician Dr Alison Poulton said an estimated 1 percent of Australian children use stimulant medication for ADHD. Medication can improve symptoms, but dosage needs to be better tailored to individual needs.

“More carefully monitored studies are needed to understand the risks and benefits of using higher doses of ADHD stimulant medications for patients who are heavier, whose ADHD may be more severe or people whose bodies break down the drug more quickly,” she said.

The meta-analysis, published in JAMA Pediatrics today, examined 49 international studies administering a common stimulant by titration (testing a range of doses to find the best dose for the individual) to over 6800 children and adolescents with ADHD.

It found wide variation in the reporting of dose ranges for stimulant medication. Not all studies reported the justification for the chosen dose range. Others used dosages inconsistent with their references or drew on information provided by the pharmaceutical manufacturer.

The researchers say that most studies to date have focused on the safety and efficacy of stimulant medication and that there is little evidence around maximum doses.

The study states: “This lack of evidence has not prevented guidelines being written up that specify apparently arbitrary dose limitations, which could discourage clinicians from titrating… to higher and perhaps for some patients, more efficacious doses.”

Lack of consistency

“There are often conflicting recommended maximum levels across various jurisdictions and from different organisations which leads to further confusion,” said Dr Poulton, Senior Lecturer in Paediatrics & Child Health and a member of the University of Sydney’s Charles Perkins Centre, Nepean.

“It concerns me that clinicians treating people with ADHD use these recommendations as a formal guide.”

“The evidence for any set maximum dose appears limited and as such the current guidelines are quite arbitrary,” said co-author Guy Eslick, Professor of Cancer Epidemiology and Medical Statistics at the University of Sydney.

Undertreated ADHD

Dr Poulton said the personal and societal costs of undertreated ADHD are huge.

“Teenagers sometimes stop taking their stimulant medication because they outgrow the dose and it stops working. These are often the most severely affected young people who are at risk of dropping out of school and into drugs and delinquency.

“Furthermore, if a doctor prescribes the recommended upper levels of stimulants and the patient is still experiencing problems the doctor may start adding other drugs to the mix. Using a mix of drugs can increase the  risk of side effects and drug interactions.”

Safety and adverse events

While the current analysis noted an absence of any reported life-threatening adverse events from stimulant use, it only analysed the most common adverse events reported in each study.

Consistent with the 2015 Cochrane Review, the analysis showed substantial risk of adverse events such as anorexia, insomnia and headache.

Disclosures: Dr Poulton reported personal fees and nonfinancial support from Shire Australia Pty Ltd (now part of Takeda Pharmaceuticals Company Ltd) outside of the submitted work. No other disclosures were reported.