Article Review: Comparative Efficacy And Tolerability Of Antidepressants For Major Depressive Disorder in Children and Adolescents: A Network Meta-Analysis


Major Depressive Disorder (MDD) is one of the most common mental disorders in children and adolescents. The researchers noted estimates suggesting it affects about 3 percent of children aged 6 to 12, and 6 percent of teens aged 13 to 18. Whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. The use of antidepressants among U.S. and U.K. children and teenagers up to age 19 has continued to increase. Antidepressant use among children and teens rose from 1.3 to 1.6 percent between 2005 and 2012, according to a separate study published in The Lancet. The U.S National Institutes of Health estimates that some 2.8 million children (or about 11 percent) between the ages of 12 and 17 have suffered from at least one episode of depression.


Depressive symptoms in children and adolescents are rather undifferentiated. You notice more irritability, aggressive behavior and problems at school. Consequences of depressive episodes in children and adolescents are dramatic because they include impairments in their social functioning, but also an increased risk of suicidal ideation and attempts. According to a study conducted by researchers from McGill University in Montreal, and published in the Journal of the American Medical Association (JAMA), nearly half of people taking depressants are not suffering from depression at all. After researchers analyzed a decade of antidepressant prescription records, they concluded that only 55 percent were given for depression, while the remaining 45 percent was written for conditions such as anxiety, sleeping problems, pain, panic disorders and Attention Deficit Hyperactivity Disorder (ADHD).


For this study, researchers of the University of Oxford conducted a systematic meta-analysis of both published and unpublished randomized control trials on the use of antidepressants for the treatment of major depression in children and young adults up to May 31, 2015. They examined trials on fourteen different antidepressants: amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. They aimed to compare and rank antidepressants and placebo for MDD in young people. The study also used the Cochrane risk of bias measures to account for the quality of the included studies. The bias analysis was essential to their conclusions as 88 percent of all of the trials were found to have a risk for bias and 65 percent of all of the trials were funded by drug companies.


They found 34 trials eligible, including 5,260 participants ages 9 to 18. Researchers discovered, for efficacy, only fluoxetine was statistically significantly more effective than placebo. In terms of tolerability, fluoxetine was also better than duloxetine and imipramine. Children taking venlafaxine actually showed an increased risk of suicidal thoughts and attempts. Nortriptyline was less effective than seven other antidepressants and the placebo. Imipramine, venlafaxine and duloxetine were the least tolerable, with many patients discontinuing them.


When considering the risk–benefit profile of antidepressants in the acute treatment of MDD, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. The lack of individual-level data from trials makes it difficult to get accurate estimates of just how these drugs affect patients, and how many become suicidal. The authors warn that this doesn’t paint a full picture, since a lack of reliable data did not allow them to fully assess the risk of suicidality for all drugs. That’s partly because 65 percent of the trials they reviewed were funded by pharmaceutical companies. So those reports could have overestimated how well their drugs worked and minimized the side effects.


The authors suggest that parents and medical professionals monitor children and adolescents taking antidepressants closely, regardless of the drug chosen. The brains in children and teens are not yet developed, so it’s important to lead with caution when prescribing medication.


Cipriani, A., Zhou, X., Giovane, C.D.; Hetrick, S.E.; Qin, B., Whittington, C.,…Coghill, D. (2016). Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. The Lancet. DOI:


Jonathan Torres, M.S.
WKPIC Doctoral Intern


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