ADHD medications: ‘huge’ variability in efficacy and tolerability

By Nicole MacKee
Research evaluating the comparative efficacy and tolerability of medications for attention deficit hyperactivity disorder (ADHD) reveals a ‘huge variability’ in patient response to drug therapy, a leading Australian child and adolescent psychiatrist says.

In a network meta-analysis published in The Lancet Psychiatry, researchers evaluated the findings of 133 randomised controlled trials that included more than 14,000 children and adolescents and 10,000 adults.

After considering both efficacy on ADHD core symptoms and safety, the researchers found methylphenidate to be the preferred medication to manage ADHD in children and adolescents, with amphetamines preferred in adults.

The researchers reviewed both published and unpublished trials comparing seven drugs – amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate and modafinil – with each other or placebo over 12 weeks.

Professor Alasdair Vance, Head of the Academic Child Psychiatry Unit at Melbourne’s Royal Children’s Hospital, told Medicine Today that the ‘deeper truth’ revealed in the findings was the huge variability in effectiveness and tolerability of these medications.

The researchers found that clinicians rated all drugs as superior to placebo in manag- ing symptoms in children and adolescents, but teachers rated only methylphenidate and modafinil as more effective than placebo. Teachers were not included in studies evaluating amphetamines and clonidine.

In terms of tolerability, methylphenidate was the only drug with better acceptability than placebo in children and adolescents.

‘The key message in this research is just how varied the response is to these medications in children and adolescents, let alone adults,’ Professor Vance said.

‘The fact that only methylphenidate emerged as a primary treatment that could be supported in children and adolescents is a striking finding.’

Professor Vance said there was a ‘massive gulf ’ between the findings of clinical quantitative research studies into groups of children and adolescents, and the unique response or nonresponse of every patient.

‘This research focused on medication to the exclusion of the psychosocial, cultural, holistic context of management that occurs in the real world,’ he said.

He noted that European guidelines and the UK’s National Institute for Health and Care Excellence (NICE) guidelines both emphasised the importance of psychosocial management as first-line treatment, with medication added only if psychosocial approaches were not successful, or the symptoms were severe.
Lancet Psychiatry 2018; 5: 727-738.