Neither of the two drugs used most frequently to prevent migraines in children is more effective than a sugar pill, according to a study published last week in The New England Journal Of Medicine.
Researchers stopped the large trial early, saying the evidence was clear even though the drugs - the antidepressant amitriptyline and the epilepsy drug topiramate - had been shown to prevent migraines in adults.
"The medication did not perform as well as we thought it would and the placebo performed better than you would think," said Dr Scott Powers, lead author of the study and a director of the Headache Centre at Cincinnati Children's Hospital Medical Centre.
Am I now going to feel obligated to tell patients that these drugs are no better than a placebo? No.
I'll simply say, 'We have data in adults that it's effective, but less convincing data in children and adolescents.'
DR EUGENE SCHNITZLER, a professor of neurology and paediatrics at Loyola University Chicago's Stritch School of Medicine.
A migraine is a neurological illness characterised by a pulsating headache, sometimes accompanied by nausea, vomiting and sensitivity to light and noise. It is a common childhood condition.
Up to 11 per cent of children aged seven to 11 and 23 per cent of 15- year-olds have migraines.
At 31 sites in the United States, 328 migraine sufferers aged eight to 17 were randomly assigned to take amitriptyline, topiramate or a placebo pill for 24 weeks. Patients with episodic migraines (fewer than 15 headache days a month) and chronic migraines (15 or more headache days a month) were included.
The aim was to figure out which drug was more effective at reducing the number of headache days and to gauge which one helped children to stop missing school or social activities.
As it turned out, there was no significant difference among the groups: 61 per cent of the placebo group reduced their headache days 50 per cent or more, compared with 52 per cent of the children given amitriptyline and 55 per cent of those who took topiramate.
And there was no significant difference among the three groups in reducing the school days or other activities missed.
The drugs also produced side effects in some children, such as fatigue, dry mouth and tingling in their hands or feet. A few cases were more severe.
One child on topiramate attempted suicide. Three taking amitriptyline had mood changes; one told his mother he wanted to hurt himself, while another wrote suicide notes at school and was hospitalised.
Because of the side effects, Dr Powers and his colleagues questioned whether the benefits of either drug outweighed the risks.
In 2014, the Food and Drug Administration (FDA) approved topiramate for the prevention of migraine headaches in adolescents aged 12 to 17 who had fewer than 15 headache days a month.
Dr Powers said that in the light of the new study, he hoped the FDA and doctors would re-examine that decision.
Other experts were not yet ready to give up on drug treatment.
"Am I now going to feel obligated to tell patients that these drugs are no better than a placebo? No," said Dr Eugene Schnitzler, a professor of neurology and paediatrics at Loyola University Chicago's Stritch School of Medicine.
"I'll simply say, 'We have data in adults that it's effective, but less convincing data in children and adolescents'."
Even if the drugs are not effective for children overall, "that doesn't mean that for any one individual, a drug might not work", said Dr David Gloss, a neurologist and a methodologist for the American Academy of Neurology.
A team of physicians, including Dr Gloss, are revising the academy's guidelines on paediatric migraines and planning to assess non- drug approaches.
A trial published last year found that taking amitriptyline and learning coping skills in a cognitive behavioural therapy programme more effectively reduced headache days for chronic sufferers aged 10 to 17 than when the drug is given with only basic headache education.