A clear winner emerges from among 14 drug treatments, but more quality data is needed
Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated for children and adolescents with major depressive disorder, according to a meta-analysis published in The Lancet.
A review of 34 trials comprising 5260 participants with an average age of 9-18 years found fluoxetine was the only drug among 14 that was significantly more effective at relieving the symptoms of depression than placebo.
Fluoxetine also had higher tolerability than the drugs duloxetine and imipramine.
Meanwhile, taking venlafaxine was linked with an increased risk of engaging in suicidal thoughts and attempts.
Altogether, the researchers reviewed trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine.
“The balance of risks and benefits of antidepressants for the treatment of major depression does not seem to offer a clear advantage in children and teenagers, with probably only the exception of fluoxetine,” says co-author Professor Peng Xie, from The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
“We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment,” he says.
It was not possible to comprehensively assess the risk of suicidality for all drugs due to lack of reliable data, say the authors.
They warn that overall quality of evidence included in the review was low, restricting the implications of the results for future clinical practice.
For example, of the 34 trials, 22 were funded by pharmaceutical companies. Ten were rated as having high risk of bias, 20 as moderate, and four as low.
Prevalence of major depressive disorder is at 1.1% of children aged 4-11 years, and 5% of children aged 12-17 years, according to the 2015 Australian Child and Adolescent Survey of Mental Health and Wellbeing.
In an accompanying comment, Dr Jon Jureidini from the University of Adelaide questions how many more suicidal events might have been revealed in these age groups had more individual patient-level data been available.
“The effect of misreporting is that antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective than has been previously recognised, so there is little reason to think that any antidepressant is better than nothing for young people,” he says.
“We doctors and researchers are failing to meet our obligation to research participants and to our patients, and we will only succeed if independent researchers … are able to analyse individual patient-level data.”