Antidepressants may be ineffective for the treatment of major depressive disorder in children and adolescents, according to a study published in The Lancet.

Of the 14 antidepressants included in the study, only fluoxetine was more effective than placebo for lessening the symptoms of depression. Venlafaxine was associated with an increased risk of suicidal thoughts and attempts compared with placebo and 5 other antidepressants.

“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. We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment,” said researcher Peng Xie, MD, of the First Affiliated Hospital of Chongqing Medical University, in Chongqing, China.

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The meta-analysis of 34 trials included 5,260 participants and 14 antidepressants. The antidepressants included were amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine.

Fluoxetine was the only antidepressant that was significantly more effective than placebo. Fluoxetine was more tolerable compared with duloxetine (odds ratio [OR], 0.31) and imipramine (OR, 0.23). Patients who were given imipramine, venlafaxine, and duloxetine were more likely to discontinue treatment due to adverse events compared with those given placebo (OR, 5.49, 3.19, and 2.80, respectively).

The researchers noted that the evidence used in their meta-analysis was of low quality. Thus, the true efficacy and risks of antidepressants in children and adolescents is still unclear.

“Without access to individual-level data it is difficult to get accurate effect estimates and we can’t be completely confident about the accuracy of the information contained in published and unpublished trials. It has been widely argued that there needs to be a transformation of existing scientific culture to one where responsible data sharing should be the norm,” said lead researcher Andrea Cipriani, MD, PhD, of the University of Oxford in the United Kingdom.


  1. Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. The Lancet. Published online June 8, 2016; doi:10.1016/S0140-6736(16)30385-3.