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Most antidepressants ineffective, unsafe for depression in youth

Findings from a network meta-analysis indicated that out of 14 antidepressant treatments, only fluoxetine had some efficacy for treatment of major depression in youth.

“Even though psychological treatments are still considered the first-line treatment in many clinical guidelines, antidepressants are widely used in the treatment of depression in children and adolescents and the rate of prescription has increased over time. However, in 2004, the FDA cautioned practitioners on the use of antidepressants in children and adolescents because of increased suicide risk,” Andrea Cipriani, PhD, of the University of Oxford, United Kingdom, and colleagues wrote. “Consequently, the question of whether to use antidepressant drugs for the treatment of major depressive disorder in young people and, if so, which antidepressant would be preferred, remains controversial.”

To assess efficacy and safety of antidepressants for major depressive disorder in children and adolescents, researchers conducted a meta-analysis of 34 trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline and venlafaxine among 5,260 participants.

Quality of evidence was rated very low for most comparisons, according to researchers.

Fluoxetine was the only antidepressant with statistically significant efficacy compared with placebo, with a standardized mean difference of –0.51 (95% CI, –0.99 to –0.03).

Fluoxetine was more tolerable than duloxetine (OR = 0.31; 95% CI, 0.13-0.95) and imipramine (OR = 0.23; 95% CI, 0.04-0.78).

Participants who received imipramine (OR = 5.49; 95% CI, 1.96-20.86), venlafaxine (OR = 3.19; 95% CI, 1.01-18.7), and duloxetine (OR = 2.8; 95% CI, 1.2-9.42) had more discontinuations due to adverse events than those who received placebo.

“The careful study by Andreas Cipriani and colleagues in The Lancet has disturbing implications for clinical practice, concluding as it does that the risk-benefit profile of antidepressants in the acute treatment of depression does ‘not seem to offer a clear advantage for children and adolescents,’” Jon Jureidini, PhD, MB BS, FRANZCP, of the University of Adelaide, Australia, wrote in an accompanying editorial. “The case for antidepressants, including fluoxetine, is, in fact, even weaker than their meta-analysis suggests. The authors do express appropriate skepticism about the quality and potential bias of data analyzed. But, they were not able to factor in the additional problems and consequences of probable data misrepresentation by the companies that did the primary studies.” – by Amanda Oldt

Disclosure: Cipriani reports personal fees from Accord Healthcare as an expert witness

for a patent issue about quetiapine extended release. Jureidini reports the University of Adelaide has been paid by Baum, Hedlund, Aristei and Goldman, Los Angeles for his analysis and opinion about documents obtained from Forest Pharmaceuticals in relation to pediatric antidepressant randomized controlled trials. Please see the full study for a list of all authors’ relevant financial disclosures.