Which drugs are best for ADHD?

A new review has examined pharmaceutical treatments for ADHD and pinpointed those most suitable for short-term use in children and adults

Of the drugs available for ADHD, the most effective and safe for short-term treatment is methylphenidate for children, and amphetamines for adults, according to a network meta-analysis and systematic review comparing the effectiveness and safety of seven ADHD drugs against placebo.

The study, published in The Lancet Psychiatry, compared the effectiveness and side effects of amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or with placebo over 12 weeks of treatment.

However, more research to confirm longer term effects of ADHD medications is urgently needed, the authors say.

Professor David Coghill, Financial Markets Foundation Chair of Developmental Mental Health at the University of Melbourne and an honorary fellow at the Murdoch Children’s Research Institute and an author of the research, highlighted this shortcoming.

“One important limitation of the data is that there were few longer term studies so our findings can only address the short term effects of these medications,” he says.

“This is important as ADHD is a long term condition and patients often need to stay on treatment for several years.

“We have therefore made a call for more long-term studies to answer these important questions.”

The study did not include psychological therapy for ADHD, though the authors also pointed out that these should be regularly discussed with people with ADHD and carers, and possibly offered before medication if appropriate, especially in children and adolescents.

The study also excluded antipsychotic drugs and antidepressants, as these do not treat core ADHD symptoms.

“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,” says Dr Andrea Cipriani, University of Oxford, UK.

“Environmental modifications – such as changes made to minimise 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 compared the available drugs based on how effectively they reduce ADHD symptoms and improve general functioning over 12 weeks of treatment.

It also studied the drugs’ side effects (including blood pressure and weight loss), and acceptability was assessed according to how many people dropped out of trials for any reason.

Of the 133 randomised clinical trials included, 81 were in children and adolescents, 51 were in adults and one trial was in both. Of these, 89 randomised controlled trials included unpublished data or were completely unpublished.

Drug effectiveness was reviewed in 10068 children and adolescents and in 8131 adults, while side effects were evaluated in 11018 children and adolescents and 5362 adults.

Symptom rating came from teachers and clinicians for children, and for adults these were given by clinicians.

Based on clinician ratings in children and adolescents, all drugs were more effective than placebo in controlling ADHD symptoms. However teachers only rated methylphenidate and modafinil as more effective than placebo (there was no data for teacher ratings of amphetamines and clonidine).

In adults, there was no data for guanfacine and clonidine. Clinicians rated all other drugs, except modafinil, as more effective than placebo in controlling ADHD symptoms.

Comparing all seven drugs, amphetamines were more effective than modafinil, atomoxetine and methylphenidate in children, adolescents, and adults.

Generally, ADHD drugs were less effective and less tolerable for adults than children and adolescents, and the cause of this is unknown, the authors said.

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

In children and adolescents, methylphenidate was the only drug with better acceptability than placebo, and in adults, only amphetamines had better acceptability than placebo.

The authors say there was not enough evidence available to confirm whether lisdexamfetamine – which is currently recommended by UK National Institute for Health and Care Excellence (NICE) for adults with ADHD – was more effective and tolerable for adults with ADHD than other amphetamines available.

In addition, although NICE recommends atomoxetine and guanfacine as third-line drugs in children, the study found these to be as tolerable or less tolerable than placebo.

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