Most antidepressants prescribed to children and adolescents with acute major depression might not be nearly as effective as they are believed to be – and one might be harmful, according to a retrospective review published June 8 and including more than 5,000 participants.
“Our analysis found robust evidence to suggest a significantly increased risk for suicidality for young people given venlafaxine,” wrote Dr. Andrea Cipriani, Xinyu Zhou, Ph.D., and their colleagues. “Unfortunately, due to the absence of reliable data on suicidality for many antidepressants, it was not possible to comprehensively assess the risk of suicidality for all drugs.”
The review looked at 34 double-blind, randomized, controlled trials investigating at least one of 14 major drugs typically prescribed as antidepressants for pediatric patients. In addition to venlafaxine, the researchers looked at amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, and sertraline (Lancet. 2016 Jun 8. doi: 10.1016/S0140-673630385-3).
All trials were published before May 31, 2015, and were found in the PubMed, Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, and LiLACS databases, as well as regulatory agencies’ websites, and international registers for published and unpublished trials. Trials either compared one or more drugs against one another, or one or more drugs against a placebo.
Fluoxetine was the only drug found to be significantly more effective than placebo, and it also was found to be significantly more effective than nortriptyline. In addition, fluoxetine proved better tolerated than imipramine and duloxetine. “However, the clinical interpretation of these findings is limited not only by the uncertainty around these estimates, but also by the potential bias due to selective reporting and the small number of trials,” said Dr. Cipriani of the University of Oxford (England) and Dr. Zhou of the First Affiliated Hospital of Chongqing Medical University in China.
Regardless of which treatment clinicians choose, children and adolescents prescribed antidepressants should be monitored closely. Clinical guidelines for young people with major depression recommend psychotherapy, particularly cognitive-behavioral therapy or interpersonal therapy as first-line interventions, and “fluoxetine should be considered only for those patients with moderate to severe depression who do not have access to psychotherapy or have not responded to nonpharmacological interventions,” the researchers said.
The study was funded by the National Basic Research Program of China. The authors did not report any relevant financial disclosures.