Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis

This network meta-analysis (71 studies; n=9510) found fluoxetine (+/- CBT) to be the only intervention significantly more effective than pill placebo or psychological controls (SMDs ranged from −1.73 to −0.51) in the acute treatment of moderate to severe depressive disorder.

SPS commentary:

A related comment notes the finding that fluoxetine is more effective than placebo in the treatment of young people with depression is consistent with previous meta-analyses. The pharmacodynamic properties of SSRIs are however similar, and they suggest that the main finding of efficacy of fluoxetine may be a ‘historical artifact’. It was the first SSRI to market and evaluated in the only two (federally-funded) studies included in the analysis that used quality implementation methods to allow the placebo response to be low enough to identify drug-placebo differences. Other SSRIs were evaluated in industry-sponsored studies with high placebo response rates.  They suggest it is likely that any well assessed child or adolescent with depression who is suitable for an SSRI and any evidence-based flexible psychotherapy will do well. Clinicians considering an SSRI to treat a paediatric patient with depression should consider other differences between the different agents in the class, including tolerability and drug interactions. 

The comment discusses other points of interest. The meta-analysis found that venlafaxine was associated with increased suicidality (OR 8.31; 95% CrI 1.92-343.17) compared with ten other interventions; this supports recommendations to use SSRIs before SNRIs in paediatric anxiety and depressive disorders. Further, interpersonal therapy – and not CBT – was more effective than all psychological controls.

There have been few new studies of pharmacotherapy in paediatric patients, and the comment authors suggest caution when interpreting the results of the increasing number of meta-analyses in this area, which is ‘no substitute for new and innovative intervention studies’.  The researchers note that the effects of the studied interventions may vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis.


The Lancet Psychiatry

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